Clinical trial NCT01703832: Explorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects
Official title: Efficacy Profile of Neurexan® in an Experimental Acute Stress Setting - an Explorative Open-Label Study in Healthy Probands
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Stress Reaction
Keywords: acute stress reaction
stress
stress perception
physiological stress response
Neurexan
Lead sponsor: Biologische Heilmittel Heel GmbH
Sponsor class: INDUSTRY
First posted: 2012-10-11
Enrollment: 65
Sex: ALL
Minimum age (years): 31
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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®.

Eligibility criteria: 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

Primary outcomes:
measure: Acute Stress Measured by Tension
timeFrame: -210 minutes to +100 minutes
measure: Acute Stress Measured by Nervousness
timeFrame: -210 minutes to +100 minutes
Secondary outcomes:
measure: Changes in Saliva Alpha Amylase
timeFrame: -60 minute, +15 minute , + 45 minute, +100 minute
measure: Changes in Saliva Cortisol
timeFrame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
measure: Changes in Plasma Adrenocorticotropic Hormone (ACTH)
timeFrame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
measure: Changes in Plasma Cortisol
timeFrame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
measure: Changes in Plasma Catecholamines (Epinephrine)
timeFrame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
measure: Changes in Plasma Catecholamines (Norepinephrine)
timeFrame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
measure: Changes in Natural Killer (NK) Cells (Subgroup)
timeFrame: -60 minutes, +15 minutes, +45 minutes, +100 minutes
measure: Changes in Blood Pressure
timeFrame: -15 minutes, 0 minutes, +15 minutes, +45 minutes
measure: Changes in Heart Rate
timeFrame: -15 minutes, 0 minutes, +15 minutes, +45 minutes
measure: State Anxiety and Stress Perception Measured by STAI-X1
timeFrame: -90 minutes, +15 minutes, +100 minutes
measure: Psychological Questionnaire (Modified Somatic SCL90)
timeFrame: -210 minutes, +100 minutes
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Institut fur Medizinische Psychologie und Verhaltensimmunbiologie Universitatsklinikum Essen
city: Marburg
country: Germany
facility: Klinische Psychologie und Psychotherapie, Fachbereich Psychologie, Universität Marburg
Study officials:
affiliation: Institut für Medizinische und Verhaltensimmunbiologie Universitätsklinikum Essen
name: Manfred Schedlowski, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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