Back to resultsA Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability (HYPERNUTRI)
Primary Purpose
Stress, Psychological
Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Prebiotic
L-Tryptophan
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Stress, Psychological
Eligibility Criteria
Inclusion Criteria: Age 18 till 40 years (both included) BMI range: 18.5 - 25 kg/m² Females: Use of contraceptives, and have to use the current contraceptive method for at least 4 months. A regular menstrual cycle (between 25 and 35 days; if not using oral contraceptives) Subject is willing to not consume caffeine, or alcohol, to refrain from smoking, and not to engage in heavy physical exercise three days before the test days, as well as to not consume dairy products and chewing gum the day before and the day of the test days Subject is willing to not take any non-steroidal anti-inflammatory drugs (NSAIDs) two weeks before the test days (see Appendix G for an overview of NSAIDs) Subject, upon briefing of the content of the present study, fully understands and agrees to its objective and has given written (dated and signed) informed consent form to take part in the study Subject is able to communicate well with the investigator and follow instructions given by the investigator Exclusion Criteria: Subject has a previous or current neurological, psychiatric, gastrointestinal, or endocrine disorder, or other relevant medical history Subject has one or more diagnoses based on the MINI international neuropsychiatric interview Subject has one or more diagnoses based on the ROME-IV for GI disorders Subject uses regular medication (i.e., anti-allergy medication, PPI's, and medication that can affect gut motility), currently or recently (in the last 2 weeks) (except for oral contraceptives) Subject has used recreational drugs in the past 6 months Subject consumes regularly (>1/week) more than 3 units of alcohol per day Subjects smokes >7 cigarettes per week Subject has to work in night-shifts Subject is pregnant or lactating Subject has previous experience with the stress test used in the study Subject has taken prebiotics or probiotics in the last month Subject has taken antibiotics in the last 3 months Subjects consumes >25g of fiber per day in their habitual diet
Sites / Locations
- KU Leuven/ UZ LeuvenRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Prebiotic
L-Tryptophan
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Executive functions during a prolonged stress task (the Leuven Prolonged Stress Test)
Working memory, cognitive flexibility, and response inhibition. Working memory will be assessed using the forward digit span. Cognitive flexibility will be assessed using the Wisconsin Card Sorting Test. Response inhibition will be assessed using the Stop Signal Task.
Secondary Outcome Measures
Intestinal permeability after a prolonged stress task (the Leuven Prolonged Stress Test)
Intestinal permeability will be measured using the lactulose-mannitol test. The lactulose-mannitol ratio will be calculated and used as a measure for small intestinal permeability. Fractional excretion of lactulose and mannitol will also be assessed.
Stress response to a prolonged stress test (the Leuven Prolonged Stress Test)
Cortisol, blood pressure, and subjective stress. Cortisol will be measured in saliva. Subjective stress will be measured using a Visual Analogue Scale (VAS)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT06089811
Brief Title
A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability
Acronym
HYPERNUTRI
Official Title
A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 10, 2023 (Actual)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
KU Leuven
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 interaction between the gut microbiome, the intestinal barrier, and the host plays an important role in human health. The integrity of the intestinal barrier is essential to protect against translocation of food antigens and immunostimulatory microbial metabolites from the gut lumen. Accumulating studies show that stress may negatively affect the intestinal barrier function. In a previous study, the investigators developed the Leuven Prolonged Acute Stress Test (L-PAST), which combines physical (cold water), mental (arithmetic), and social (negative feedback) aspects of stress for a prolonged (2h) time. In the current study the investigators would like, as a first aim, to investigate whether the L-PAST 1) increases intestinal permeability compared to baseline intestinal permeability, and 2) whether a nutritional intervention can improve baseline intestinal permeability as well as intestinal permeability after exposure to the L-PAST in both healthy females and men. As a second aim of the present study, the investigators would like to investigate whether prebiotics and/or L-tryptophan can attenuate the cortisol response to stress. Lastly, as acute psychosocial stress impairs cognitive functions, the investigators would like as a third aim to investigate whether prebiotics and/or L-tryptophan supplementation may prevent these impairments.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stress, Psychological
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The present study is a parallel group randomized controlled trial (RCT) aiming to investigate whether two nutritional interventions (prebiotics and L-tryptophan) can improve intestinal barrier function, attenuate the stress response, affect cognitive processes, and prevent stress-induced hyperpermeability. Participants will perform 2 study visits of 3h each and with 28 days in between, in which participants will be subjected to the L-PAST. During the L-PAST, 3 cognitive tasks will be administered. Moreover, participants will be asked to take a basal intestinal permeability test at home 2 days before the test days.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Participants, investigators, and personnel involved in data analyses are blinded to the intervention. Unblinding occurs after all data has been collected AND analysed.
Allocation
Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Prebiotic
Arm Type
Experimental
Arm Title
L-Tryptophan
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Dietary Supplement
Intervention Name(s)
Prebiotic
Intervention Description
Group 1 (prebiotic and placebo L-tryptophan): prebiotic (oligofructose, Orafti®P95, 20g/day) and placebo L-tryptophan (microcrystalline cellulose, 3g/day)
Intervention Type
Dietary Supplement
Intervention Name(s)
L-Tryptophan
Intervention Description
Group 2 (placebo prebiotic and L-tryptophan): L-tryptophan (3g/day) and placebo prebiotic (microcrystalline cellulose, 20g/day)
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Group 3 (placebo prebiotic and placebo L-tryptophan): placebo prebiotic (microcrystalline cellulose, 20g/day) and placebo L-tryptophan (microcrystalline cellulose, 3g/day).
Primary Outcome Measure Information:
Title
Executive functions during a prolonged stress task (the Leuven Prolonged Stress Test)
Description
Working memory, cognitive flexibility, and response inhibition. Working memory will be assessed using the forward digit span. Cognitive flexibility will be assessed using the Wisconsin Card Sorting Test. Response inhibition will be assessed using the Stop Signal Task.
Time Frame
Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.
Secondary Outcome Measure Information:
Title
Intestinal permeability after a prolonged stress task (the Leuven Prolonged Stress Test)
Description
Intestinal permeability will be measured using the lactulose-mannitol test. The lactulose-mannitol ratio will be calculated and used as a measure for small intestinal permeability. Fractional excretion of lactulose and mannitol will also be assessed.
Time Frame
Measured at the pre-intervention and immediately after the 4 week intervention.
Title
Stress response to a prolonged stress test (the Leuven Prolonged Stress Test)
Description
Cortisol, blood pressure, and subjective stress. Cortisol will be measured in saliva. Subjective stress will be measured using a Visual Analogue Scale (VAS)
Time Frame
During the stress task (at multiple time points during 120 min), measured at the pre-intervention and immediately after the 4 week intervention.
Other Pre-specified Outcome Measures:
Title
Intestinal permeability baseline
Description
Intestinal permeability will be measured using the lactulose-mannitol test. The lactulose-mannitol ratio will be calculated and used as a measure for small intestinal permeability. Fractional excretion of lactulose and mannitol will also be assessed.
Time Frame
Measured 2 days before the pre-intervention and immediately after the 4 week intervention.
Title
Short chain fatty acids
Description
Short chain fatty acids will be measured both in feces and serum.
Time Frame
Measured for 3h during the pre-intervention and immediately after the 4 week intervention.
Title
Tryptophan metabolites
Description
Tryptophan metabolites (kynurenine and indole pathway) will be measured in urine and blood.
Time Frame
Measured in blood for 3h during the pre-intervention and immediately after the 4 week intervention. Urine will be collected 3 days prior to the pre-intervention and immediately after the 4 week intervention.
Title
Inflammatory cytokines
Description
Including interleukin (IL)-1β, IL-6, IL-10, IL-13, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α
Time Frame
Measured at the pre-intervention and immediately after the 4 week intervention.
Title
Subjective pain response to the prolonged stress test
Description
The subjective pain response to the prolonged stress task (Leuven Prolonged Stress Test) will be measured using a Visual Analogue Scale (VAS) (1-100)
Time Frame
Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.
Title
Cognitive reactivity to failure response to the prolonged stress test
Description
Cognitive reactivity to failure response to the prolonged stress task (Leuven Prolonged Stress Test) will be assessed using two rating scales on a scale of 0 to 100. On one scale, 0 means 'I feel much less self-assured than before, 50 means 'I feel as self-assured as before, and 100 means 'I feel much more self-assured than before'. On the other scale, 0 means 'I think I'm not good at anything at all, 50 means 'I still think the same about myself', and 100 means 'I think I can achieve anything'.
Time Frame
Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.
Title
Perceived Stress Scale (PSS)
Description
The Perceived Stress Scale (PSS) is a 14-item instrument designed to measure the degree to which situations in one's life are appraised as stressful. It provides a tool for examining issues about the role of appraised stress levels in the etiology of disease and behavioral disorders. The scale is designed such that it asks the respondent to rate the frequency of his/her feelings and thoughts related to events and situations that occurred over a selected time-frame. Notably, high PSS scores have been correlated with higher biomarkers of stress, such as cortisol.
Time Frame
Measured at the pre-intervention and immediately after the 4 week intervention.
Title
Gastrointestinal symptom rating scale (GSRS)
Description
The Gastrointestinal Symptom Rating Scale (GSRS) is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The reliability and validity of the GSRS are well-documented, and norm values for a general population are available.
Time Frame
Measured at the pre-intervention and immediately after the 4 week intervention.
Title
Patient Health Questionnaire 9 (PHQ-9)
Description
The Patient Health Questionnaire - 9 (PHQ-9) is a 9-item questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). This self-report measure determines the severity of depression symptoms and is frequently used to monitor changes in symptom severity over time in non-psychiatric settings. Subjects are asked to rate each of the items on a scale of 0 to 3 on the basis of how much a symptom has bothered them over the last 2 weeks (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day).
Time Frame
Measured at the pre-intervention and immediately after the 4 week intervention.
Title
Generalized Anxiety Questionnaire 7 (GAD-7)
Description
The Generalized Anxiety Questionnaire (GAD-7) is a 7-item questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). This self-report measure reflects the frequency of anxiety symptoms over the past 2 weeks. Subjects are asked to rate each of the items on a scale of 0 to 3 on the basis of how much a symptom has bothered them over the last 2 weeks (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day).
Time Frame
Measured at the pre-intervention and immediately after the 4 week intervention.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age 18 till 40 years (both included)
BMI range: 18.5 - 25 kg/m²
Females: Use of contraceptives, and have to use the current contraceptive method for at least 4 months. A regular menstrual cycle (between 25 and 35 days; if not using oral contraceptives)
Subject is willing to not consume caffeine, or alcohol, to refrain from smoking, and not to engage in heavy physical exercise three days before the test days, as well as to not consume dairy products and chewing gum the day before and the day of the test days
Subject is willing to not take any non-steroidal anti-inflammatory drugs (NSAIDs) two weeks before the test days (see Appendix G for an overview of NSAIDs)
Subject, upon briefing of the content of the present study, fully understands and agrees to its objective and has given written (dated and signed) informed consent form to take part in the study
Subject is able to communicate well with the investigator and follow instructions given by the investigator
Exclusion Criteria:
Subject has a previous or current neurological, psychiatric, gastrointestinal, or endocrine disorder, or other relevant medical history
Subject has one or more diagnoses based on the MINI international neuropsychiatric interview
Subject has one or more diagnoses based on the ROME-IV for GI disorders
Subject uses regular medication (i.e., anti-allergy medication, PPI's, and medication that can affect gut motility), currently or recently (in the last 2 weeks) (except for oral contraceptives)
Subject has used recreational drugs in the past 6 months
Subject consumes regularly (>1/week) more than 3 units of alcohol per day
Subjects smokes >7 cigarettes per week
Subject has to work in night-shifts
Subject is pregnant or lactating
Subject has previous experience with the stress test used in the study
Subject has taken prebiotics or probiotics in the last month
Subject has taken antibiotics in the last 3 months
Subjects consumes >25g of fiber per day in their habitual diet
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Danique La Torre, MSc
Phone
+3216373499
Email
danique.latorre@kuleuven.be
First Name & Middle Initial & Last Name or Official Title & Degree
Kristin Verbeke, PhD
Phone
+3216330150
Email
kristin.verbeke@kuleuven.be
Facility Information:
Facility Name
KU Leuven/ UZ Leuven
City
Leuven
State/Province
Vlaams-Brabant
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Danique La Torre, MSc
Phone
+3216373499
Email
danique.latorre@kuleuven.be
First Name & Middle Initial & Last Name & Degree
Kristin Verbeke, PhD
Phone
+3216330150
Email
kristin.verbeke@kuleuven.be
First Name & Middle Initial & Last Name & Degree
Kristin Verbeke, PhD
First Name & Middle Initial & Last Name & Degree
Lukas Van Oudenhove, PhD, MD
First Name & Middle Initial & Last Name & Degree
Tim Vanuytsel, PhD, MD
First Name & Middle Initial & Last Name & Degree
Danique La Torre, MSc
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability
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