Back to resultsExplorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects (NEUPRO-OL)
Primary Purpose
Acute Stress Reaction
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Neurexan®
Sponsored by
About this trial
This is an interventional treatment trial for Acute Stress Reaction focused on measuring acute stress reaction, stress, stress perception, physiological stress response, Neurexan
Eligibility Criteria
Inclusion Criteria:
- Provide written informed consent
- Healthy male or female
- age between 31 to 59 years
- Fluent in German language.
- Ability to understand the explanations and instructions given by the study physician
Exclusion Criteria:
- allergies to ingredients of Neurexan® (Passiflora incarnata, Avena sativa, Coffea arabica, Zincum isovalerianicum, lactose monohydrate, magnesium stearate)
- lactose intolerance
- use of any psychological stress-management intervention within the last 4 weeks
- sick leave for any reason
- participation in any other clinical study 3 months prior to Screening Visit
- current or recent (3 months prior to Screening Visit) history of substance abuse or drug dependence including nicotine and alcohol (as verified in the respective IDCL list)
- smokers
- alcohol intake within last 24 hours (before Baseline Visit V3)
- shift workers or work regularly during night time
- use of any psychotropic medication or suffering from severe psychiatric illness needing acute intervention
- BMI > 30 kg/m2
- currently pregnant (verified by urine pregnancy test) or lactating
- participation in a previous TSST study
- high chronic stress as verified with the TICS-SSCS (a score of ≥ 23 on the screening scale for chronic stress meets the criterion of being chronically stressed)
- major mental disorder as verified with the IDCL (depressive episode, panic disorder, social phobia, obsessive-compulsory disorder; alcohol dependency; schizophrenia and mania.)
- employee of the Sponsor, one of the investigators or the CRO
- use of any concomitant medication except contraceptives
- any somatic disease or other condition the Investigator or their duly assigned representatives believes may affect the ability of the individual to complete the study or the interpretation of the study results
- Individuals whose ability to speak for themselves lacks or can be doubted
Sites / Locations
- Institut fur Medizinische Psychologie und Verhaltensimmunbiologie Universitatsklinikum Essen
- Klinische Psychologie und Psychotherapie, Fachbereich Psychologie, Universität Marburg
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Neurexan®
No intervention
Arm Description
0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes
no tablet intake and subjects will undergo the natural course
Outcomes
Primary Outcome Measures
Acute Stress Measured by Tension
Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.
Acute Stress Measured by Nervousness
Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.
Secondary Outcome Measures
Changes in Saliva Alpha Amylase
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Changes in Saliva Cortisol
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Changes in Plasma Adrenocorticotropic Hormone (ACTH)
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Changes in Plasma Cortisol
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Changes in Plasma Catecholamines (Epinephrine)
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Changes in Plasma Catecholamines (Norepinephrine)
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Changes in Natural Killer (NK) Cells (Subgroup)
The Natural Killer Cells as immune cells and stress biomarkers were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Changes in Blood Pressure
Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.
The measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.
Changes in Heart Rate
Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.
The measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.
State Anxiety and Stress Perception Measured by STAI-X1
State anxiety and stress perception were measured by State-Trait Anxiety Inventory X1 before and after a stress test. The measurements took place 90 minutes before stress test and were repeated 15 and 100 minutes after the end of the stress test. The German version of the State-Trait-Anxiety Inventory was used and differentiates between temporary/emotional state anxiety versus personality trait anxiety. The two scales with 20 items each assess (1) anxiety as a trait (STAI-X2) and (2) anxiety as a state (STAI-XI). Answers are given in a 4-point rating scale ranging from 1 ="not at all" to 4 ="very true". For analysis of each, STAI-scale single scores were summed up to one total score, representing the state and trait anxiety. Score range is 20-80 and higher scores indicate a higher anxiety.
Psychological Questionnaire (Modified Somatic SCL90)
The SCL90 has 90 items with dimensions like depression, somatization, obsessive-compulsive disorder, social insecurity, anxiety, phobic anxiety, aggression/hostility, paranoid ideation, psychoticism and each item in a subscale ranged from 0 to 4. The lower range values are favorable outcomes and higher are worse outcomes. The modified somatic SCL90 uses the SCL90 somatization items, but instead of a 7 day timeframe asks for "now". The corresponding items from SCL90 were: 1, 4, 12, 27, 40, 42, 48, 49, 52, 53, 56, 58 and the introductory question: "How much do you currently suffer from" ("Wie sehr leiden Sie momentan unter:"). The median of the average Modified Somatic SCL90 score is reported. The average score was calculated at each time point as the sum score divided by the number of non-missing individual question results for subjects with no more than 2 missing responses. The lower values in the range represent favorable outcomes while the higher values represent worse outcomes.
Full Information
NCT ID
NCT01703832
First Posted
October 8, 2012
Last Updated
February 9, 2015
Sponsor
Biologische Heilmittel Heel GmbH
1. Study Identification
Unique Protocol Identification Number
NCT01703832
Brief Title
Explorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects
Acronym
NEUPRO-OL
Official Title
Efficacy Profile of Neurexan® in an Experimental Acute Stress Setting - an Explorative Open-Label Study in Healthy Probands
Study Type
Interventional
2. Study Status
Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biologische Heilmittel Heel GmbH
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to explore the efficacy of acutely dosed Neurexan using an experimental stress test called the Trier Social Stress Test
Detailed Description
An acute stress reaction is a biopsychological condition arising in response to an event which is individually regarded as emotionally stressful. The onset of a stress response is associated with specific physiological actions in the sympathetic nervous system, both directly and indirectly through the release of adrenaline and to a lesser extent noradrenaline from the medulla of the adrenal glands. These catecholamine hormones facilitate immediate physical reactions by triggering increases in heart rate and breathing, constricting blood vessels. The other major player in the acute stress response is the hypothalamic-pituitary-adrenal axis.
Although stress has been described as a non-specific psychophysiological response to environmental stimuli, it is possible to discern specific bodily stress responses caused by specific emotional reactions to novel, ambivalent or uncontrollable situations and stimuli. For example, social stress induces elevated cortisol levels, particularly if the stressor is uncontrollable, unpredictable, and constitutes a social-evaluative threat due to the judgment of others such as in the Trier Social Stress Test). Usually, the TSST induces a two-fold increase in saliva cortisol with peaks around 10-20 min. after stress test termination. Also, an average increase in heart rates of around 20 beats per minute (bpm) is observed during the TSST. In addition, emotional states and feelings have been shown to be affected by this stress test, such as marked increases in stress perception,anxiety and emotional insecurity as well as decreases in mood, calmness and feeling awake.
Preliminary results indicate that Neurexan® may improve coping abilities in stressful situations. This study aims to investigate the effect of Neurexan® on subjectively perceived nervousness and tension during an acute stressful situation and to characterize the efficacy profile of Neurexan®.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Stress Reaction
Keywords
acute stress reaction, stress, stress perception, physiological stress response, Neurexan
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Neurexan®
Arm Type
Experimental
Arm Description
0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes
Arm Title
No intervention
Arm Type
No Intervention
Arm Description
no tablet intake and subjects will undergo the natural course
Intervention Type
Drug
Intervention Name(s)
Neurexan®
Intervention Description
0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes
Primary Outcome Measure Information:
Title
Acute Stress Measured by Tension
Description
Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.
Time Frame
-210 minutes to +100 minutes
Title
Acute Stress Measured by Nervousness
Description
Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.
Time Frame
-210 minutes to +100 minutes
Secondary Outcome Measure Information:
Title
Changes in Saliva Alpha Amylase
Description
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Time Frame
-60 minute, +15 minute , + 45 minute, +100 minute
Title
Changes in Saliva Cortisol
Description
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Time Frame
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Title
Changes in Plasma Adrenocorticotropic Hormone (ACTH)
Description
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Time Frame
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Title
Changes in Plasma Cortisol
Description
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Time Frame
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Title
Changes in Plasma Catecholamines (Epinephrine)
Description
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Time Frame
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Title
Changes in Plasma Catecholamines (Norepinephrine)
Description
The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Time Frame
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Title
Changes in Natural Killer (NK) Cells (Subgroup)
Description
The Natural Killer Cells as immune cells and stress biomarkers were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.
Time Frame
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Title
Changes in Blood Pressure
Description
Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.
The measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.
Time Frame
-15 minutes, 0 minutes, +15 minutes, +45 minutes
Title
Changes in Heart Rate
Description
Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.
The measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.
Time Frame
-15 minutes, 0 minutes, +15 minutes, +45 minutes
Title
State Anxiety and Stress Perception Measured by STAI-X1
Description
State anxiety and stress perception were measured by State-Trait Anxiety Inventory X1 before and after a stress test. The measurements took place 90 minutes before stress test and were repeated 15 and 100 minutes after the end of the stress test. The German version of the State-Trait-Anxiety Inventory was used and differentiates between temporary/emotional state anxiety versus personality trait anxiety. The two scales with 20 items each assess (1) anxiety as a trait (STAI-X2) and (2) anxiety as a state (STAI-XI). Answers are given in a 4-point rating scale ranging from 1 ="not at all" to 4 ="very true". For analysis of each, STAI-scale single scores were summed up to one total score, representing the state and trait anxiety. Score range is 20-80 and higher scores indicate a higher anxiety.
Time Frame
-90 minutes, +15 minutes, +100 minutes
Title
Psychological Questionnaire (Modified Somatic SCL90)
Description
The SCL90 has 90 items with dimensions like depression, somatization, obsessive-compulsive disorder, social insecurity, anxiety, phobic anxiety, aggression/hostility, paranoid ideation, psychoticism and each item in a subscale ranged from 0 to 4. The lower range values are favorable outcomes and higher are worse outcomes. The modified somatic SCL90 uses the SCL90 somatization items, but instead of a 7 day timeframe asks for "now". The corresponding items from SCL90 were: 1, 4, 12, 27, 40, 42, 48, 49, 52, 53, 56, 58 and the introductory question: "How much do you currently suffer from" ("Wie sehr leiden Sie momentan unter:"). The median of the average Modified Somatic SCL90 score is reported. The average score was calculated at each time point as the sum score divided by the number of non-missing individual question results for subjects with no more than 2 missing responses. The lower values in the range represent favorable outcomes while the higher values represent worse outcomes.
Time Frame
-210 minutes, +100 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
31 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Provide written informed consent
Healthy male or female
age between 31 to 59 years
Fluent in German language.
Ability to understand the explanations and instructions given by the study physician
Exclusion Criteria:
allergies to ingredients of Neurexan® (Passiflora incarnata, Avena sativa, Coffea arabica, Zincum isovalerianicum, lactose monohydrate, magnesium stearate)
lactose intolerance
use of any psychological stress-management intervention within the last 4 weeks
sick leave for any reason
participation in any other clinical study 3 months prior to Screening Visit
current or recent (3 months prior to Screening Visit) history of substance abuse or drug dependence including nicotine and alcohol (as verified in the respective IDCL list)
smokers
alcohol intake within last 24 hours (before Baseline Visit V3)
shift workers or work regularly during night time
use of any psychotropic medication or suffering from severe psychiatric illness needing acute intervention
BMI > 30 kg/m2
currently pregnant (verified by urine pregnancy test) or lactating
participation in a previous TSST study
high chronic stress as verified with the TICS-SSCS (a score of ≥ 23 on the screening scale for chronic stress meets the criterion of being chronically stressed)
major mental disorder as verified with the IDCL (depressive episode, panic disorder, social phobia, obsessive-compulsory disorder; alcohol dependency; schizophrenia and mania.)
employee of the Sponsor, one of the investigators or the CRO
use of any concomitant medication except contraceptives
any somatic disease or other condition the Investigator or their duly assigned representatives believes may affect the ability of the individual to complete the study or the interpretation of the study results
Individuals whose ability to speak for themselves lacks or can be doubted
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manfred Schedlowski, PhD
Organizational Affiliation
Institut für Medizinische und Verhaltensimmunbiologie Universitätsklinikum Essen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut fur Medizinische Psychologie und Verhaltensimmunbiologie Universitatsklinikum Essen
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Klinische Psychologie und Psychotherapie, Fachbereich Psychologie, Universität Marburg
City
Marburg
ZIP/Postal Code
35032
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
17615391
Citation
McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007 Jul;87(3):873-904. doi: 10.1152/physrev.00041.2006.
Results Reference
background
PubMed Identifier
16952284
Citation
Elsenbruch S, Lucas A, Holtmann G, Haag S, Gerken G, Riemenschneider N, Langhorst J, Kavelaars A, Heijnen CJ, Schedlowski M. Public speaking stress-induced neuroendocrine responses and circulating immune cell redistribution in irritable bowel syndrome. Am J Gastroenterol. 2006 Oct;101(10):2300-7. doi: 10.1111/j.1572-0241.2006.00837.x. Epub 2006 Sep 4.
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
21689890
Citation
Hellhammer J, Schubert M. The physiological response to Trier Social Stress Test relates to subjective measures of stress during but not before or after the test. Psychoneuroendocrinology. 2012 Jan;37(1):119-24. doi: 10.1016/j.psyneuen.2011.05.012.
Results Reference
background
PubMed Identifier
19837490
Citation
Schult J, Hero T, Hellhammer J. Effects of powdered fertilized eggs on the stress response. Clin Nutr. 2010 Apr;29(2):255-60. doi: 10.1016/j.clnu.2009.09.004. Epub 2009 Oct 17.
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
5535207
Citation
Weiss JM. Somatic effects of predictable and unpredictable shock. Psychosom Med. 1970 Jul-Aug;32(4):397-408. doi: 10.1097/00006842-197007000-00008. No abstract available.
Results Reference
background
PubMed Identifier
10600217
Citation
Pawlak CR, Jacobs R, Mikeska E, Ochsmann S, Lombardi MS, Kavelaars A, Heijnen CJ, Schmidt RE, Schedlowski M. Patients with systemic lupus erythematosus differ from healthy controls in their immunological response to acute psychological stress. Brain Behav Immun. 1999 Dec;13(4):287-302. doi: 10.1006/brbi.1999.0553.
Results Reference
background
PubMed Identifier
8598500
Citation
Schedlowski M, Hosch W, Oberbeck R, Benschop RJ, Jacobs R, Raab HR, Schmidt RE. Catecholamines modulate human NK cell circulation and function via spleen-independent beta 2-adrenergic mechanisms. J Immunol. 1996 Jan 1;156(1):93-9.
Results Reference
background
PubMed Identifier
9491439
Citation
Schmid-Ott G, Jacobs R, Jager B, Klages S, Wolf J, Werfel T, Kapp A, Schurmeyer T, Lamprecht F, Schmidt RE, Schedlowski M. Stress-induced endocrine and immunological changes in psoriasis patients and healthy controls. A preliminary study. Psychother Psychosom. 1998;67(1):37-42. doi: 10.1159/000012257.
Results Reference
background
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Explorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects
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