Back to resultsStress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects
Primary Purpose
Healthy, Stress, Psychological
Status
Completed
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Lpc-37
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Healthy focused on measuring Probiotic, Gut-brain axis, Stress, Anxiety
Eligibility Criteria
Inclusion Criteria:
- Voluntary, written, informed consent to participate in the study
- Male or female aged between 18-45 years (inclusive)
- Body mass index (BMI) between 18.5 - 29.9 kg/m2
- Medical examination at baseline indicates they are healthy in the opinion of the investigator
- Ability of the participant (in the Principal Investigator's opinion) to comprehend the full nature and purpose of the study including possible risks and side effects
- Agreement to comply with the protocol and study restrictions
- Available for all study visits
- Females of child-bearing potential required to provide a negative urine pregnancy test and to use contraceptives
- Easy access to internet
Exclusion Criteria:
- Self-reported diagnosis of one or more Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV axis 1 disorder(s), including but not limited to current major depression, anxiety disorder, bipolar spectrum disorder or schizophrenia
- Have a significant acute or chronic coexisting illness (cardiovascular, gastrointestinal (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD)), immunological, metabolic, neurodevelopmental or any condition which contraindicates, in the Investigator's judgement, entry to the study
- Currently taking (from day of screening onwards) or have previously taken (last 4 weeks prior to screening) psychoactive medication (anxiolytics, sedatives, hypnotics, anti-psychotics, anti-depressants, anti-convulsants, centrally acting corticosteroids, opioid pain relievers)
- Currently taking (from day of screening onwards) medication or dietary supplements that the Investigator believes would interfere with the objectives of the study, pose a safety risk or confound the interpretation of the study results (e.g. melatonin, omega-3 dietary supplements, non-steroidal anti-inflammatory drugs (NSAIDS), over-the-counter (OTC) sleep medication (not categorized as sedatives, hypnotics or anti-depressants), anti-coagulants, proton pump inhibitors, anti-histamines, pseudoephedrine, cortisone, beta-blockers)
- Recent (within last 4 weeks prior to screening) or ongoing antibiotic therapy during the intervention period
- Daily consumption of concentrated sources of probiotics and/or prebiotics within 2 weeks of screening and throughout the intervention period other than the provided study products (e.g., probiotic/prebiotic tablets, capsules, drops or powders)
- Pregnant or lactating female, or pregnancy planned during intervention period
- Not fluent in German
- Have self-reported dyslexia
- History of alcohol, drug, or medication abuse
- Self-declared illicit drug users (including cannabis and cocaine) for 3 weeks prior to screening and during the intervention period
- Contraindication to any substance in the investigational product
- Hypertension (systolic ≥ 140 mmHg, diastolic ≥ 90 mmHg)
- Known hyper- or hypothyroidism unless treated and under control (stable for more than 3 months)
- Subjects having previously participated in the TSST
- Smoking > 5 cigarettes/day
- Employee of the sponsor or contract research organization (CRO)
- Participation in another study with any investigational product within 60 days of screening and during the intervention period
- Investigator believes that the participant may be uncooperative and/or noncompliant and should therefore not participate in the study
- Participant under administrative or legal supervision
Sites / Locations
- daacro GmbH & Co. KG
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Lpc-37
Placebo
Arm Description
Lacticaseibacillus paracasei Lpc-37 (Lpc-37), formerly Lactobacillus paracasei Lpc-37 1x 1 capsule in the morning for 5 weeks
Placebo capsule manufactured to mimic Lpc-37 capsule 1x 1 capsule in the morning for 5 weeks
Outcomes
Primary Outcome Measures
Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST)
Efficacy was defined as a lower increase in HR in response to the TSST following intervention with Lpc-37, compared to placebo.
Secondary Outcome Measures
Changes in Pre and Post Treatment STAI-state Scores
Efficacy of the intake of Lpc-37 on the reduction of State-Trait-Anxiety-Inventory (STAI)-state scores compared to placebo.
Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety.
Changes in Pre and Post Treatment Perceived Stress Scale (PSS) Scores
Efficacy of the intake of Lpc-37 on the reduction of Perceived Stress Scale (PSS) scores compared to placebo.
Measured with the german version of the PSS as a psychological instrument for measuring stress perception. It assesses how unpredictable, uncontrollable and overloaded participants perceived their lives to have been within the last month. The PSS comprises 14 items that are answered on a five-point rating scale ranging from 0 = "never" to 4 = "very often". Individual scores on the PSS can range from 0 to 56 with higher scores indicating higher perceived stress.
Changes in Pre and Post Treatment DASS Depression Scores
Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) depression scores compared to placebo.
Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.
Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items.
The Depression scale assesses dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest/involvement, anhedonia, and inertia. The items are 3, 5, 10, 13, 16, 17, 21, 24, 26, 31, 34, 37, 38, 42 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms.
Changes in Pre and Post Treatment DASS Anxiety Scores
Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) anxiety scores compared to placebo.
Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.
Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items.
The anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxious affect. The items are 2, 4, 7, 9, 15, 19, 20, 23, 25, 28, 30, 36, 40, 41 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms.
Changes in Pre and Post Treatment DASS Stress Scores
Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) stress scores compared to placebo.
Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.
Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items.
The stress scale (items) is sensitive to levels of chronic non-specific arousal.The stress scale items are 1, 6, 8, 11, 12, 14, 18, 22, 27, 29, 32, 33, 35, 39 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms.
Changes in Pre and Post Treatment BAI Scores
Efficacy of the intake of Lpc-37 on the reduction of Beck Anxiety Inventory (BAI) scores compared to placebo.
Measured with the german version of the Beck Anxiety Inventory as a self-rating scale designed to measure anxiety. It comprises 21 sentences describing feelings that can occur when being anxious. These sentences are rated on a four-point rating scale ranging from 0="not at all" to 3="severely", considering the last 7 days. The score range is 0-63; Higher scores indicate higher anxiety.
Changes in Pre and Post Treatment VAS Stress Perception Scores
Efficacy of the intake of Lpc-37 on the reduction of Visual Analog Scale (VAS) stress perception scores compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress.
Changes in Pre and Post Treatment VAS Anxiety Scores
Efficacy of the intake of Lpc-37 on the reduction of VAS anxiety scores compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety.
Changes in Pre and Post Treatment VAS Insecurity Scores
Efficacy of the intake of Lpc-37 on the reduction of VAS insecurity scores compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity.
Changes in Pre and Post Treatment VAS Exhaustion Scores
Efficacy of the intake of Lpc-37 on the reduction of VAS exhaustion scores compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion.
Changes in Pre and Post Treatment Systolic BP
Efficacy of the intake of Lpc-37 on the reduction of systolic blood pressure (BP).
Changes in Pre and Post Treatment Diastolic BP
Efficacy of the intake of Lpc-37 on the reduction of diastolic BP.
Change of STAI-State Scores in Response to the TSST
Efficacy of the intake of Lpc-37 on reduction of the increase of STAI-State scores in response to the TSST compared to placebo.
Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety.
Change of Systolic BP in Response to the TSST
Efficacy of the intake of Lpc-37 on reduction of the increase of the systolic BP in response to the TSST compared to placebo.
Change of Diastolic Blood Pressure (BP) in Response to the TSST
Efficacy of the intake of Lpc-37 on reduction of the increase of the diastolic BP in response to the TSST compared to placebo.
Change of VAS Stress Perception Scores in Response to the TSST
Efficacy of the intake of Lpc-37 on reduction of the increase of VAS Stress perception scores in response to the TSST compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress.
Change of VAS Anxiety Scores in Response to the TSST
Efficacy of the intake of Lpc-37 on reduction of the increase of VAS anxiety scores in response to the TSST compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety.
Change of VAS Insecurity Scores in Response to the TSST
Efficacy of the intake of Lpc-37 on reduction of the increase of VAS insecurity scores in response to the TSST compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity.
Change of VAS Exhaustion Scores in Response to the TSST
Efficacy of the intake of Lpc-37 on reduction of the increase of VAS exhaustion scores in response to the TSST compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion.
Change of Salivary Cortisol in Response to the TSST
Efficacy of the intake of Lpc-37 on reduction of the increase of salivary cortisol in response to the TSST compared to placebo.
Change of sAA in Response to the TSST
Efficacy of the intake of Lpc-37 on reduction of the increase of salivary Alpha-Amylase (sAA) in response to the TSST compared to placebo.
Change of Sleep Duration Over the Course of the Treatment
Efficacy of the intake of Lpc-37 on the increase of sleep duration over the course of the treatment.
Sleep duration was monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for Sleep duration for the averaged ratings per participant and week
Change of Sleep Related Recovery Scores Over the Course of the Treatment
Efficacy of the intake of Lpc-37 on the increase of sleep related recovery scores over the course of the treatment.
Measured with a daily online diary. Sleep related recovery was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored throughout the wash-out phase (Week 1 and 2) and the subsequent treatment phase (weeks 3-7). High scores indicate a high recovery.
Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for sleep related recovery for the averaged ratings per participant and week.
Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total)
Efficacy of the intake of Lpc-37 on the decrease of sleep disruptions over the course of the treatment measured with a daily online diary (Proportion (yes/total)).
Sleep disruptions were monitored through the wash-out phase and the subsequent treatment phase for each week. In the binary version, the value is either Yes or No for each day and each participant.
Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant.
The proportion of participants with at least one sleep disruption by treatment group is given, treatment commenced after week 2. Data listed here reflect the proportion of participants who answered "Yes" (e.g. 0,477 * 44 = 20.99 participants answered with "Yes" in week 1 in the Lpc-37 group).
Change of Reported Number of Sleep Disruptions Over the Course of the Treatment
Efficacy of the intake of Lpc-37 on the decrease of reported number of sleep disruptions over the course of the treatment measured with a daily online diary (mean of week summary).
Sleep disruptions were monitored through the wash-out phase (Week 1 and 2) and the subsequent treatment phase (Weeks 3-7). In the count version, the value can be 0 or a natural number for each day and each participant. Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for sleep disruptions (count) for the summed counts per participant and week.
Change of Perceived Health Status Scores Over the Course of the Treatment
Efficacy of the intake of Lpc-37 on the increase of perceived health status scores over the course of the treatment.
Measured with a daily online diary. Health status was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a high perceived health.Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for perceived health status on a scale from 0 to 10 for the averaged ratings per participant and week.
Change of Mood Scale Scores Over the Course of the Treatment
Efficacy of the intake of Lpc-37 on the increase of mood scale scores over the course of the treatment
Measured with a daily online diary. Mood was rated by participants on an 11-point scale (0-10; "very bad" to "very well") and monitored through the washout phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a better mood. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one average value for each week and participant. Values reflect summary measures for mood ratings on a scale from 0 to 10 for the averaged ratings per participant and week.
Change of Perceived Productivity Scores Over the Course of the Treatment
Efficacy of the intake of Lpc-37 on the increase of perceived productivity scores over the course of the treatment
Measured with a daily online diary. Productivity was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a higher perceived productivity. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group.Time is coded as a continuous variable with one value for each day and participant. The values reflect summary measures for perceived productivity on a scale from 0 to 10 for the averaged ratings per participant and week.
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures
Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol Awakening Response (CAR) area under the curve with respect to the ground (AUCg) values to the respective mean before and after 5 weeks of treatment.
The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCg is the total area under the curve of all measurements (i.e., the intensity or magnitude of the response).
Efficacy for the CAR variables AUCg is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures
Efficacy of the intake of Lpc-37 on the reduction of the difference of CAR area under the curve with respect to the increase (AUCi) values to the respective mean before and after the treatment.
The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCi is calculated with reference to the baseline measurement and it ignores the distance from zero for all measurements and emphasizes the changes over time. Efficacy for the CAR variables AUCi is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures
Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol at Awakening values to the respective mean before and after 5 weeks of treatment
Efficacy for the CAR variable cortisol at awakening is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures
Efficacy of the intake of Lpc-37 on the reduction of the difference of cortisol at 8 pm values to the respective mean before and after 5 weeks of treatment
Efficacy for the CAR variable cortisol at 8 pm is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.
Full Information
NCT ID
NCT03494725
First Posted
April 4, 2018
Last Updated
February 24, 2021
Sponsor
Daacro
Collaborators
DuPont Nutrition and Health
1. Study Identification
Unique Protocol Identification Number
NCT03494725
Brief Title
Stress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects
Official Title
Proof-of-Concept "Stress & Anxiety Dampening Effects of Lpc-37"
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
April 10, 2018 (Actual)
Primary Completion Date
October 9, 2018 (Actual)
Study Completion Date
October 9, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Daacro
Collaborators
DuPont Nutrition and Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this study is to assess whether a 5 week intake of a probiotic (Lpc-37) can modulate stress and anxiety experienced by healthy subjects during and after an acute stressor compared to placebo. To measure stress and anxiety, markers of the hypothalamic-pituitary-adrenal (HPA) axis activity and questionnaires will be assessed before, during and after the Trier Social Stress Test (TSST). The results of this study indicate if the chosen study design is suitable to discover stress-related effects of probiotics.
Detailed Description
The total mass of microorganisms residing within the human intestine is approximately the same as that of the human brain. Of late, these >1000 species and >7000 strains have been described as the "brain in our belly" because of the essential role they play in physiological and psychological health and disease. The gut-brain axis describes the bidirectional communication that exists between the brain and the gut and the microbiota-gut-brain axis supports the role of the gut microbiome in this communication system. Emotional and routine daily life stress can disrupt digestive function, but increasing evidence indicates that the gut microbiota exert a profound influence on brain physiology, psychological responses and ultimately behavior.
A plethora of literature to date, albeit predominantly preclinical, have demonstrated evidence to support the role of the gut microbiome in regulating stress-related changes in physiology, behavior and brain function.
Stress is an individual process to deal with external and internal challenges that ranges from behavioral to molecular adaptations. The HPA axis and its release of stress hormones plays a major role in stress adaptation.
The purpose of this clinical trial is to determine whether a single strain of bacteria derived from the species Lacticaseibacillus paracasei Lpc-37 (Lpc-37), formerly Lactobacillus paracasei Lpc-37, can modulate stress experienced by healthy subjects exposed to the TSST measured by HPA axis activation markers and self-report questionnaires.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Stress, Psychological
Keywords
Probiotic, Gut-brain axis, Stress, Anxiety
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lpc-37
Arm Type
Active Comparator
Arm Description
Lacticaseibacillus paracasei Lpc-37 (Lpc-37), formerly Lactobacillus paracasei Lpc-37
1x 1 capsule in the morning for 5 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsule manufactured to mimic Lpc-37 capsule
1x 1 capsule in the morning for 5 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Lpc-37
Intervention Description
Lacticaseibacillus paracasei Lpc-37 at 1.75 x 10^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
microcrystalline cellulose, magnesium stearate, silicon dioxide
Primary Outcome Measure Information:
Title
Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST)
Description
Efficacy was defined as a lower increase in HR in response to the TSST following intervention with Lpc-37, compared to placebo.
Time Frame
Continuous measurement starting 20 minutes before and ending 20 minutes after the TSST after 5 weeks of product intake. Mean values were calculated per group at seven-time windows before, during and after the TSST
Secondary Outcome Measure Information:
Title
Changes in Pre and Post Treatment STAI-state Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of State-Trait-Anxiety-Inventory (STAI)-state scores compared to placebo.
Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment Perceived Stress Scale (PSS) Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of Perceived Stress Scale (PSS) scores compared to placebo.
Measured with the german version of the PSS as a psychological instrument for measuring stress perception. It assesses how unpredictable, uncontrollable and overloaded participants perceived their lives to have been within the last month. The PSS comprises 14 items that are answered on a five-point rating scale ranging from 0 = "never" to 4 = "very often". Individual scores on the PSS can range from 0 to 56 with higher scores indicating higher perceived stress.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment DASS Depression Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) depression scores compared to placebo.
Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.
Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items.
The Depression scale assesses dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest/involvement, anhedonia, and inertia. The items are 3, 5, 10, 13, 16, 17, 21, 24, 26, 31, 34, 37, 38, 42 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment DASS Anxiety Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) anxiety scores compared to placebo.
Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.
Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items.
The anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxious affect. The items are 2, 4, 7, 9, 15, 19, 20, 23, 25, 28, 30, 36, 40, 41 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment DASS Stress Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) stress scores compared to placebo.
Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.
Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items.
The stress scale (items) is sensitive to levels of chronic non-specific arousal.The stress scale items are 1, 6, 8, 11, 12, 14, 18, 22, 27, 29, 32, 33, 35, 39 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment BAI Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of Beck Anxiety Inventory (BAI) scores compared to placebo.
Measured with the german version of the Beck Anxiety Inventory as a self-rating scale designed to measure anxiety. It comprises 21 sentences describing feelings that can occur when being anxious. These sentences are rated on a four-point rating scale ranging from 0="not at all" to 3="severely", considering the last 7 days. The score range is 0-63; Higher scores indicate higher anxiety.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment VAS Stress Perception Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of Visual Analog Scale (VAS) stress perception scores compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment VAS Anxiety Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of VAS anxiety scores compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment VAS Insecurity Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of VAS insecurity scores compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment VAS Exhaustion Scores
Description
Efficacy of the intake of Lpc-37 on the reduction of VAS exhaustion scores compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion.
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment Systolic BP
Description
Efficacy of the intake of Lpc-37 on the reduction of systolic blood pressure (BP).
Time Frame
Before and after 5 weeks of study product intake.
Title
Changes in Pre and Post Treatment Diastolic BP
Description
Efficacy of the intake of Lpc-37 on the reduction of diastolic BP.
Time Frame
Before and after 5 weeks of study product intake.
Title
Change of STAI-State Scores in Response to the TSST
Description
Efficacy of the intake of Lpc-37 on reduction of the increase of STAI-State scores in response to the TSST compared to placebo.
Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety.
Time Frame
10 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake
Title
Change of Systolic BP in Response to the TSST
Description
Efficacy of the intake of Lpc-37 on reduction of the increase of the systolic BP in response to the TSST compared to placebo.
Time Frame
3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake
Title
Change of Diastolic Blood Pressure (BP) in Response to the TSST
Description
Efficacy of the intake of Lpc-37 on reduction of the increase of the diastolic BP in response to the TSST compared to placebo.
Time Frame
3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake
Title
Change of VAS Stress Perception Scores in Response to the TSST
Description
Efficacy of the intake of Lpc-37 on reduction of the increase of VAS Stress perception scores in response to the TSST compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress.
Time Frame
10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake
Title
Change of VAS Anxiety Scores in Response to the TSST
Description
Efficacy of the intake of Lpc-37 on reduction of the increase of VAS anxiety scores in response to the TSST compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety.
Time Frame
10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake
Title
Change of VAS Insecurity Scores in Response to the TSST
Description
Efficacy of the intake of Lpc-37 on reduction of the increase of VAS insecurity scores in response to the TSST compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity.
Time Frame
10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake
Title
Change of VAS Exhaustion Scores in Response to the TSST
Description
Efficacy of the intake of Lpc-37 on reduction of the increase of VAS exhaustion scores in response to the TSST compared to placebo.
Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion.
Time Frame
10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake
Title
Change of Salivary Cortisol in Response to the TSST
Description
Efficacy of the intake of Lpc-37 on reduction of the increase of salivary cortisol in response to the TSST compared to placebo.
Time Frame
1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake
Title
Change of sAA in Response to the TSST
Description
Efficacy of the intake of Lpc-37 on reduction of the increase of salivary Alpha-Amylase (sAA) in response to the TSST compared to placebo.
Time Frame
1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake
Title
Change of Sleep Duration Over the Course of the Treatment
Description
Efficacy of the intake of Lpc-37 on the increase of sleep duration over the course of the treatment.
Sleep duration was monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for Sleep duration for the averaged ratings per participant and week
Time Frame
Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
Title
Change of Sleep Related Recovery Scores Over the Course of the Treatment
Description
Efficacy of the intake of Lpc-37 on the increase of sleep related recovery scores over the course of the treatment.
Measured with a daily online diary. Sleep related recovery was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored throughout the wash-out phase (Week 1 and 2) and the subsequent treatment phase (weeks 3-7). High scores indicate a high recovery.
Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for sleep related recovery for the averaged ratings per participant and week.
Time Frame
Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
Title
Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total)
Description
Efficacy of the intake of Lpc-37 on the decrease of sleep disruptions over the course of the treatment measured with a daily online diary (Proportion (yes/total)).
Sleep disruptions were monitored through the wash-out phase and the subsequent treatment phase for each week. In the binary version, the value is either Yes or No for each day and each participant.
Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant.
The proportion of participants with at least one sleep disruption by treatment group is given, treatment commenced after week 2. Data listed here reflect the proportion of participants who answered "Yes" (e.g. 0,477 * 44 = 20.99 participants answered with "Yes" in week 1 in the Lpc-37 group).
Time Frame
Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
Title
Change of Reported Number of Sleep Disruptions Over the Course of the Treatment
Description
Efficacy of the intake of Lpc-37 on the decrease of reported number of sleep disruptions over the course of the treatment measured with a daily online diary (mean of week summary).
Sleep disruptions were monitored through the wash-out phase (Week 1 and 2) and the subsequent treatment phase (Weeks 3-7). In the count version, the value can be 0 or a natural number for each day and each participant. Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for sleep disruptions (count) for the summed counts per participant and week.
Time Frame
Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
Title
Change of Perceived Health Status Scores Over the Course of the Treatment
Description
Efficacy of the intake of Lpc-37 on the increase of perceived health status scores over the course of the treatment.
Measured with a daily online diary. Health status was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a high perceived health.Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for perceived health status on a scale from 0 to 10 for the averaged ratings per participant and week.
Time Frame
Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
Title
Change of Mood Scale Scores Over the Course of the Treatment
Description
Efficacy of the intake of Lpc-37 on the increase of mood scale scores over the course of the treatment
Measured with a daily online diary. Mood was rated by participants on an 11-point scale (0-10; "very bad" to "very well") and monitored through the washout phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a better mood. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one average value for each week and participant. Values reflect summary measures for mood ratings on a scale from 0 to 10 for the averaged ratings per participant and week.
Time Frame
Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
Title
Change of Perceived Productivity Scores Over the Course of the Treatment
Description
Efficacy of the intake of Lpc-37 on the increase of perceived productivity scores over the course of the treatment
Measured with a daily online diary. Productivity was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a higher perceived productivity. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group.Time is coded as a continuous variable with one value for each day and participant. The values reflect summary measures for perceived productivity on a scale from 0 to 10 for the averaged ratings per participant and week.
Time Frame
Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
Title
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures
Description
Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol Awakening Response (CAR) area under the curve with respect to the ground (AUCg) values to the respective mean before and after 5 weeks of treatment.
The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCg is the total area under the curve of all measurements (i.e., the intensity or magnitude of the response).
Efficacy for the CAR variables AUCg is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.
Time Frame
Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)
Title
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures
Description
Efficacy of the intake of Lpc-37 on the reduction of the difference of CAR area under the curve with respect to the increase (AUCi) values to the respective mean before and after the treatment.
The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCi is calculated with reference to the baseline measurement and it ignores the distance from zero for all measurements and emphasizes the changes over time. Efficacy for the CAR variables AUCi is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.
Time Frame
Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)
Title
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures
Description
Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol at Awakening values to the respective mean before and after 5 weeks of treatment
Efficacy for the CAR variable cortisol at awakening is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.
Time Frame
Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)
Title
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures
Description
Efficacy of the intake of Lpc-37 on the reduction of the difference of cortisol at 8 pm values to the respective mean before and after 5 weeks of treatment
Efficacy for the CAR variable cortisol at 8 pm is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.
Time Frame
Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Voluntary, written, informed consent to participate in the study
Male or female aged between 18-45 years (inclusive)
Body mass index (BMI) between 18.5 - 29.9 kg/m2
Medical examination at baseline indicates they are healthy in the opinion of the investigator
Ability of the participant (in the Principal Investigator's opinion) to comprehend the full nature and purpose of the study including possible risks and side effects
Agreement to comply with the protocol and study restrictions
Available for all study visits
Females of child-bearing potential required to provide a negative urine pregnancy test and to use contraceptives
Easy access to internet
Exclusion Criteria:
Self-reported diagnosis of one or more Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV axis 1 disorder(s), including but not limited to current major depression, anxiety disorder, bipolar spectrum disorder or schizophrenia
Have a significant acute or chronic coexisting illness (cardiovascular, gastrointestinal (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD)), immunological, metabolic, neurodevelopmental or any condition which contraindicates, in the Investigator's judgement, entry to the study
Currently taking (from day of screening onwards) or have previously taken (last 4 weeks prior to screening) psychoactive medication (anxiolytics, sedatives, hypnotics, anti-psychotics, anti-depressants, anti-convulsants, centrally acting corticosteroids, opioid pain relievers)
Currently taking (from day of screening onwards) medication or dietary supplements that the Investigator believes would interfere with the objectives of the study, pose a safety risk or confound the interpretation of the study results (e.g. melatonin, omega-3 dietary supplements, non-steroidal anti-inflammatory drugs (NSAIDS), over-the-counter (OTC) sleep medication (not categorized as sedatives, hypnotics or anti-depressants), anti-coagulants, proton pump inhibitors, anti-histamines, pseudoephedrine, cortisone, beta-blockers)
Recent (within last 4 weeks prior to screening) or ongoing antibiotic therapy during the intervention period
Daily consumption of concentrated sources of probiotics and/or prebiotics within 2 weeks of screening and throughout the intervention period other than the provided study products (e.g., probiotic/prebiotic tablets, capsules, drops or powders)
Pregnant or lactating female, or pregnancy planned during intervention period
Not fluent in German
Have self-reported dyslexia
History of alcohol, drug, or medication abuse
Self-declared illicit drug users (including cannabis and cocaine) for 3 weeks prior to screening and during the intervention period
Contraindication to any substance in the investigational product
Hypertension (systolic ≥ 140 mmHg, diastolic ≥ 90 mmHg)
Known hyper- or hypothyroidism unless treated and under control (stable for more than 3 months)
Subjects having previously participated in the TSST
Smoking > 5 cigarettes/day
Employee of the sponsor or contract research organization (CRO)
Participation in another study with any investigational product within 60 days of screening and during the intervention period
Investigator believes that the participant may be uncooperative and/or noncompliant and should therefore not participate in the study
Participant under administrative or legal supervision
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juliane Hellhammer, PhD
Organizational Affiliation
Daacro GmbH & Co. KG
Official's Role
Principal Investigator
Facility Information:
Facility Name
daacro GmbH & Co. KG
City
Trier
State/Province
Rhineland-Palatinate
ZIP/Postal Code
54296
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
10461128
Citation
Bailey MT, Coe CL. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev Psychobiol. 1999 Sep;35(2):146-55.
Results Reference
background
PubMed Identifier
21040780
Citation
Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun. 2011 Mar;25(3):397-407. doi: 10.1016/j.bbi.2010.10.023. Epub 2010 Oct 30.
Results Reference
background
PubMed Identifier
15085020
Citation
Bailey MT, Lubach GR, Coe CL. Prenatal stress alters bacterial colonization of the gut in infant monkeys. J Pediatr Gastroenterol Nutr. 2004 Apr;38(4):414-21. doi: 10.1097/00005176-200404000-00009.
Results Reference
background
PubMed Identifier
21683077
Citation
Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, Deng Y, Blennerhassett P, Macri J, McCoy KD, Verdu EF, Collins SM. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011 Aug;141(2):599-609, 609.e1-3. doi: 10.1053/j.gastro.2011.04.052. Epub 2011 Apr 30.
Results Reference
background
PubMed Identifier
21988661
Citation
Bercik P, Park AJ, Sinclair D, Khoshdel A, Lu J, Huang X, Deng Y, Blennerhassett PA, Fahnestock M, Moine D, Berger B, Huizinga JD, Kunze W, McLean PG, Bergonzelli GE, Collins SM, Verdu EF. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil. 2011 Dec;23(12):1132-9. doi: 10.1111/j.1365-2982.2011.01796.x. Epub 2011 Oct 11.
Results Reference
background
PubMed Identifier
26479188
Citation
Bharwani A, Mian MF, Foster JA, Surette MG, Bienenstock J, Forsythe P. Structural & functional consequences of chronic psychosocial stress on the microbiome & host. Psychoneuroendocrinology. 2016 Jan;63:217-27. doi: 10.1016/j.psyneuen.2015.10.001. Epub 2015 Oct 9.
Results Reference
background
PubMed Identifier
21876150
Citation
Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5. doi: 10.1073/pnas.1102999108. Epub 2011 Aug 29.
Results Reference
background
PubMed Identifier
22688187
Citation
Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, Dinan TG, Cryan JF. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry. 2013 Jun;18(6):666-73. doi: 10.1038/mp.2012.77. Epub 2012 Jun 12.
Results Reference
background
PubMed Identifier
24590859
Citation
Daulatzai MA. Chronic functional bowel syndrome enhances gut-brain axis dysfunction, neuroinflammation, cognitive impairment, and vulnerability to dementia. Neurochem Res. 2014 Apr;39(4):624-44. doi: 10.1007/s11064-014-1266-6. Epub 2014 Mar 4.
Results Reference
background
Citation
Dallman, M. F., & Hellhammer, D. (2011). Regulation of the hypothalamo-pituitaryadrenal axis, chronic stress, and energy: the role of brain networks. The handbook of stress science: Biology, psychology, and health, 11-36.
Results Reference
background
PubMed Identifier
24412651
Citation
De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Backhed F, Mithieux G. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014 Jan 16;156(1-2):84-96. doi: 10.1016/j.cell.2013.12.016. Epub 2014 Jan 9.
Results Reference
background
PubMed Identifier
18456279
Citation
Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74. doi: 10.1016/j.jpsychires.2008.03.009. Epub 2008 May 5.
Results Reference
background
PubMed Identifier
20696216
Citation
Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010 Nov 10;170(4):1179-88. doi: 10.1016/j.neuroscience.2010.08.005. Epub 2010 Aug 6.
Results Reference
background
PubMed Identifier
15122924
Citation
Dickerson SS, Kemeny ME. Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull. 2004 May;130(3):355-91. doi: 10.1037/0033-2909.130.3.355.
Results Reference
background
PubMed Identifier
27048547
Citation
Dinan TG, Cryan JF. Mood by microbe: towards clinical translation. Genome Med. 2016 Apr 6;8(1):36. doi: 10.1186/s13073-016-0292-1.
Results Reference
background
PubMed Identifier
23759244
Citation
Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013 Nov 15;74(10):720-6. doi: 10.1016/j.biopsych.2013.05.001. Epub 2013 Jun 10.
Results Reference
background
PubMed Identifier
25772005
Citation
Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015 Apr;63:1-9. doi: 10.1016/j.jpsychires.2015.02.021. Epub 2015 Mar 3.
Results Reference
background
PubMed Identifier
26438800
Citation
Foster JA, Lyte M, Meyer E, Cryan JF. Gut Microbiota and Brain Function: An Evolving Field in Neuroscience. Int J Neuropsychopharmacol. 2016 Apr 29;19(5):pyv114. doi: 10.1093/ijnp/pyv114. Print 2016 May.
Results Reference
background
PubMed Identifier
23384445
Citation
Foster JA, McVey Neufeld KA. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013 May;36(5):305-12. doi: 10.1016/j.tins.2013.01.005. Epub 2013 Feb 4.
Results Reference
background
PubMed Identifier
29276734
Citation
Foster JA, Rinaman L, Cryan JF. Stress & the gut-brain axis: Regulation by the microbiome. Neurobiol Stress. 2017 Mar 19;7:124-136. doi: 10.1016/j.ynstr.2017.03.001. eCollection 2017 Dec.
Results Reference
background
PubMed Identifier
18854200
Citation
Fries E, Dettenborn L, Kirschbaum C. The cortisol awakening response (CAR): facts and future directions. Int J Psychophysiol. 2009 Apr;72(1):67-73. doi: 10.1016/j.ijpsycho.2008.03.014. Epub 2008 Sep 30.
Results Reference
background
PubMed Identifier
26135201
Citation
Golubeva AV, Crampton S, Desbonnet L, Edge D, O'Sullivan O, Lomasney KW, Zhdanov AV, Crispie F, Moloney RD, Borre YE, Cotter PD, Hyland NP, O'Halloran KD, Dinan TG, O'Keeffe GW, Cryan JF. Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood. Psychoneuroendocrinology. 2015 Oct;60:58-74. doi: 10.1016/j.psyneuen.2015.06.002. Epub 2015 Jun 17.
Results Reference
background
PubMed Identifier
21282636
Citation
Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, Samuelsson A, Hibberd ML, Forssberg H, Pettersson S. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3047-52. doi: 10.1073/pnas.1010529108. Epub 2011 Jan 31.
Results Reference
background
PubMed Identifier
8234641
Citation
Hellhammer DH, Wade S. Endocrine correlates of stress vulnerability. Psychother Psychosom. 1993;60(1):8-17. doi: 10.1159/000288675.
Results Reference
background
PubMed Identifier
19575614
Citation
Holsboer F, Ising M. Stress hormone regulation: biological role and translation into therapy. Annu Rev Psychol. 2010;61:81-109, C1-11. doi: 10.1146/annurev.psych.093008.100321.
Results Reference
background
PubMed Identifier
25592533
Citation
Janak PH, Tye KM. From circuits to behaviour in the amygdala. Nature. 2015 Jan 15;517(7534):284-92. doi: 10.1038/nature14188.
Results Reference
background
PubMed Identifier
26079804
Citation
Jasarevic E, Howerton CL, Howard CD, Bale TL. Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain. Endocrinology. 2015 Sep;156(9):3265-76. doi: 10.1210/en.2015-1177. Epub 2015 Jun 16.
Results Reference
background
PubMed Identifier
27491067
Citation
Kelly JR, Borre Y, O' Brien C, Patterson E, El Aidy S, Deane J, Kennedy PJ, Beers S, Scott K, Moloney G, Hoban AE, Scott L, Fitzgerald P, Ross P, Stanton C, Clarke G, Cryan JF, Dinan TG. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016 Nov;82:109-18. doi: 10.1016/j.jpsychires.2016.07.019. Epub 2016 Jul 25.
Results Reference
background
PubMed Identifier
26528128
Citation
Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015 Oct 14;9:392. doi: 10.3389/fncel.2015.00392. eCollection 2015.
Results Reference
background
PubMed Identifier
8255414
Citation
Kirschbaum C, Pirke KM, Hellhammer DH. The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28(1-2):76-81. doi: 10.1159/000119004.
Results Reference
background
PubMed Identifier
20105052
Citation
Kudielka BM, Wust S. Human models in acute and chronic stress: assessing determinants of individual hypothalamus-pituitary-adrenal axis activity and reactivity. Stress. 2010 Jan;13(1):1-14. doi: 10.3109/10253890902874913.
Results Reference
background
PubMed Identifier
26912607
Citation
Luczynski P, McVey Neufeld KA, Oriach CS, Clarke G, Dinan TG, Cryan JF. Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior. Int J Neuropsychopharmacol. 2016 Aug 12;19(8):pyw020. doi: 10.1093/ijnp/pyw020. Print 2016 Aug.
Results Reference
background
PubMed Identifier
24350221
Citation
Mackowiak PA. Recycling metchnikoff: probiotics, the intestinal microbiome and the quest for long life. Front Public Health. 2013 Nov 13;1:52. doi: 10.3389/fpubh.2013.00052.
Results Reference
background
PubMed Identifier
15309418
Citation
Marcos A, Warnberg J, Nova E, Gomez S, Alvarez A, Alvarez R, Mateos JA, Cobo JM. The effect of milk fermented by yogurt cultures plus Lactobacillus casei DN-114001 on the immune response of subjects under academic examination stress. Eur J Nutr. 2004 Dec;43(6):381-9. doi: 10.1007/s00394-004-0517-8. Epub 2004 Jul 14.
Results Reference
background
PubMed Identifier
28266612
Citation
Marin IA, Goertz JE, Ren T, Rich SS, Onengut-Gumuscu S, Farber E, Wu M, Overall CC, Kipnis J, Gaultier A. Microbiota alteration is associated with the development of stress-induced despair behavior. Sci Rep. 2017 Mar 7;7:43859. doi: 10.1038/srep43859.
Results Reference
background
PubMed Identifier
4303377
Citation
Mason JW. A review of psychoendocrine research on the pituitary-adrenal cortical system. Psychosom Med. 1968 Sep-Oct;30(5):Suppl:576-607. No abstract available.
Results Reference
background
PubMed Identifier
20974015
Citation
Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011 Mar;105(5):755-64. doi: 10.1017/S0007114510004319. Epub 2010 Oct 26.
Results Reference
background
PubMed Identifier
16002223
Citation
Nater UM, La Marca R, Florin L, Moses A, Langhans W, Koller MM, Ehlert U. Stress-induced changes in human salivary alpha-amylase activity -- associations with adrenergic activity. Psychoneuroendocrinology. 2006 Jan;31(1):49-58. doi: 10.1016/j.psyneuen.2005.05.010. Epub 2005 Jul 5.
Results Reference
background
PubMed Identifier
21054680
Citation
Neufeld KM, Kang N, Bienenstock J, Foster JA. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil. 2011 Mar;23(3):255-64, e119. doi: 10.1111/j.1365-2982.2010.01620.x. Epub 2010 Nov 5.
Results Reference
background
Citation
Nishida, K., Sawada, D., Kuwano, Y., Tanaka, H., Sugawara, T., Aoki, Y., ... & Rokutan, K. (2017). Daily administration of paraprobiotic lactobacillus gasseri cp2305 ameliorates chronic stress-associated symptoms in Japanese medical students. Journal of Functional Foods, 36, 112-121.
Results Reference
background
PubMed Identifier
18723164
Citation
O'Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EM, Cryan JF, Dinan TG. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009 Feb 1;65(3):263-7. doi: 10.1016/j.biopsych.2008.06.026. Epub 2008 Aug 23.
Results Reference
background
PubMed Identifier
25078296
Citation
O'Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res. 2015 Jan 15;277:32-48. doi: 10.1016/j.bbr.2014.07.027. Epub 2014 Jul 29.
Results Reference
background
PubMed Identifier
25700599
Citation
Ogbonnaya ES, Clarke G, Shanahan F, Dinan TG, Cryan JF, O'Leary OF. Adult Hippocampal Neurogenesis Is Regulated by the Microbiome. Biol Psychiatry. 2015 Aug 15;78(4):e7-9. doi: 10.1016/j.biopsych.2014.12.023. Epub 2015 Jan 9. No abstract available.
Results Reference
background
PubMed Identifier
24756641
Citation
De Palma G, Collins SM, Bercik P, Verdu EF. The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both? J Physiol. 2014 Jul 15;592(14):2989-97. doi: 10.1113/jphysiol.2014.273995. Epub 2014 Apr 22.
Results Reference
background
PubMed Identifier
28483500
Citation
Pinto-Sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT, Martin FP, Cominetti O, Welsh C, Rieder A, Traynor J, Gregory C, De Palma G, Pigrau M, Ford AC, Macri J, Berger B, Bergonzelli G, Surette MG, Collins SM, Moayyedi P, Bercik P. Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome. Gastroenterology. 2017 Aug;153(2):448-459.e8. doi: 10.1053/j.gastro.2017.05.003. Epub 2017 May 5.
Results Reference
background
PubMed Identifier
26760398
Citation
Sherwin E, Rea K, Dinan TG, Cryan JF. A gut (microbiome) feeling about the brain. Curr Opin Gastroenterol. 2016 Mar;32(2):96-102. doi: 10.1097/MOG.0000000000000244.
Results Reference
background
PubMed Identifier
27417321
Citation
Sherwin E, Sandhu KV, Dinan TG, Cryan JF. May the Force Be With You: The Light and Dark Sides of the Microbiota-Gut-Brain Axis in Neuropsychiatry. CNS Drugs. 2016 Nov;30(11):1019-1041. doi: 10.1007/s40263-016-0370-3.
Results Reference
background
PubMed Identifier
28943228
Citation
Slykerman RF, Hood F, Wickens K, Thompson JMD, Barthow C, Murphy R, Kang J, Rowden J, Stone P, Crane J, Stanley T, Abels P, Purdie G, Maude R, Mitchell EA; Probiotic in Pregnancy Study Group. Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial. EBioMedicine. 2017 Oct;24:159-165. doi: 10.1016/j.ebiom.2017.09.013. Epub 2017 Sep 14.
Results Reference
background
PubMed Identifier
25862297
Citation
Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015 Aug;48:258-64. doi: 10.1016/j.bbi.2015.04.003. Epub 2015 Apr 7.
Results Reference
background
PubMed Identifier
26184083
Citation
Stilling RM, Ryan FJ, Hoban AE, Shanahan F, Clarke G, Claesson MJ, Dinan TG, Cryan JF. Microbes & neurodevelopment--Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala. Brain Behav Immun. 2015 Nov;50:209-220. doi: 10.1016/j.bbi.2015.07.009. Epub 2015 Jul 14.
Results Reference
background
PubMed Identifier
15133062
Citation
Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, Kubo C, Koga Y. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004 Jul 1;558(Pt 1):263-75. doi: 10.1113/jphysiol.2004.063388. Epub 2004 May 7.
Results Reference
background
PubMed Identifier
26896291
Citation
Takada M, Nishida K, Kataoka-Kato A, Gondo Y, Ishikawa H, Suda K, Kawai M, Hoshi R, Watanabe O, Igarashi T, Kuwano Y, Miyazaki K, Rokutan K. Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models. Neurogastroenterol Motil. 2016 Jul;28(7):1027-36. doi: 10.1111/nmo.12804. Epub 2016 Feb 20.
Results Reference
background
PubMed Identifier
15485637
Citation
Takai N, Yamaguchi M, Aragaki T, Eto K, Uchihashi K, Nishikawa Y. Effect of psychological stress on the salivary cortisol and amylase levels in healthy young adults. Arch Oral Biol. 2004 Dec;49(12):963-8. doi: 10.1016/j.archoralbio.2004.06.007.
Results Reference
background
PubMed Identifier
4593471
Citation
Tannock GW, Savage DC. Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infect Immun. 1974 Mar;9(3):591-8. doi: 10.1128/iai.9.3.591-598.1974.
Results Reference
background
PubMed Identifier
23474283
Citation
Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain-Raspaud S, Trotin B, Naliboff B, Mayer EA. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013 Jun;144(7):1394-401, 1401.e1-4. doi: 10.1053/j.gastro.2013.02.043. Epub 2013 Mar 6.
Results Reference
background
PubMed Identifier
12377295
Citation
Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002 Oct;53(4):865-71. doi: 10.1016/s0022-3999(02)00429-4.
Results Reference
background
PubMed Identifier
33385020
Citation
Patterson E, Griffin SM, Ibarra A, Ellsiepen E, Hellhammer J. Lacticaseibacillus paracasei Lpc-37(R) improves psychological and physiological markers of stress and anxiety in healthy adults: a randomized, double-blind, placebo-controlled and parallel clinical trial (the Sisu study). Neurobiol Stress. 2020 Nov 24;13:100277. doi: 10.1016/j.ynstr.2020.100277. eCollection 2020 Nov.
Results Reference
derived
Links:
URL
http://www.daacro.de
Description
daacro homepage
Learn more about this trial
Stress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects
We'll reach out to this number within 24 hrs