Explorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects (NEUPRO-OL)

February 9, 2015 updated by: Biologische Heilmittel Heel GmbH

Efficacy Profile of Neurexan® in an Experimental Acute Stress Setting - an Explorative Open-Label Study in Healthy Probands

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

Study Overview

Status

Completed

Intervention / Treatment

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®.

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Essen, Germany, 45122
        • Institut fur Medizinische Psychologie und Verhaltensimmunbiologie Universitatsklinikum Essen
      • Marburg, Germany, 35032
        • Klinische Psychologie und Psychotherapie, Fachbereich Psychologie, Universität Marburg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

31 years to 59 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provide written informed consent
  2. Healthy male or female
  3. age between 31 to 59 years
  4. Fluent in German language.
  5. Ability to understand the explanations and instructions given by the study physician

Exclusion Criteria:

  1. allergies to ingredients of Neurexan® (Passiflora incarnata, Avena sativa, Coffea arabica, Zincum isovalerianicum, lactose monohydrate, magnesium stearate)
  2. lactose intolerance
  3. use of any psychological stress-management intervention within the last 4 weeks
  4. sick leave for any reason
  5. participation in any other clinical study 3 months prior to Screening Visit
  6. 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)
  7. smokers
  8. alcohol intake within last 24 hours (before Baseline Visit V3)
  9. shift workers or work regularly during night time
  10. use of any psychotropic medication or suffering from severe psychiatric illness needing acute intervention
  11. BMI > 30 kg/m2
  12. currently pregnant (verified by urine pregnancy test) or lactating
  13. participation in a previous TSST study
  14. 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)
  15. major mental disorder as verified with the IDCL (depressive episode, panic disorder, social phobia, obsessive-compulsory disorder; alcohol dependency; schizophrenia and mania.)
  16. employee of the Sponsor, one of the investigators or the CRO
  17. use of any concomitant medication except contraceptives
  18. 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
  19. Individuals whose ability to speak for themselves lacks or can be doubted

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neurexan®
0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes
0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes
No Intervention: No intervention
no tablet intake and subjects will undergo the natural course

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Stress Measured by Tension
Time Frame: -210 minutes to +100 minutes
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.
-210 minutes to +100 minutes
Acute Stress Measured by Nervousness
Time Frame: -210 minutes to +100 minutes
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.
-210 minutes to +100 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Saliva Alpha Amylase
Time Frame: -60 minute, +15 minute , + 45 minute, +100 minute
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.
-60 minute, +15 minute , + 45 minute, +100 minute
Changes in Saliva Cortisol
Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
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.
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Changes in Plasma Adrenocorticotropic Hormone (ACTH)
Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
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.
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Changes in Plasma Cortisol
Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
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.
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Changes in Plasma Catecholamines (Epinephrine)
Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
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.
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Changes in Plasma Catecholamines (Norepinephrine)
Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
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.
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Changes in Natural Killer (NK) Cells (Subgroup)
Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
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.
-60 minutes, +15 minutes, +45 minutes, +100 minutes
Changes in Blood Pressure
Time Frame: -15 minutes, 0 minutes, +15 minutes, +45 minutes

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.

-15 minutes, 0 minutes, +15 minutes, +45 minutes
Changes in Heart Rate
Time Frame: -15 minutes, 0 minutes, +15 minutes, +45 minutes

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.

-15 minutes, 0 minutes, +15 minutes, +45 minutes
State Anxiety and Stress Perception Measured by STAI-X1
Time Frame: -90 minutes, +15 minutes, +100 minutes
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.
-90 minutes, +15 minutes, +100 minutes
Psychological Questionnaire (Modified Somatic SCL90)
Time Frame: -210 minutes, +100 minutes
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.
-210 minutes, +100 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Manfred Schedlowski, PhD, Institut für Medizinische und Verhaltensimmunbiologie Universitätsklinikum Essen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

October 8, 2012

First Submitted That Met QC Criteria

October 10, 2012

First Posted (Estimate)

October 11, 2012

Study Record Updates

Last Update Posted (Estimate)

February 11, 2015

Last Update Submitted That Met QC Criteria

February 9, 2015

Last Verified

February 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Stress Reaction

Clinical Trials on Neurexan®

Subscribe