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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biologische Heilmittel Heel GmbH
ClinicalTrials.gov Identifier:
NCT01703832
First received: October 8, 2012
Last updated: February 9, 2015
Last verified: February 2015
  Purpose

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


Condition Intervention Phase
Acute Stress Reaction
Drug: Neurexan®
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy Profile of Neurexan® in an Experimental Acute Stress Setting - an Explorative Open-Label Study in Healthy Probands

Further study details as provided by Biologische Heilmittel Heel GmbH:

Primary Outcome Measures:
  • Acute Stress Measured by Tension [ Time Frame: -210 minutes to +100 minutes ] [ Designated as safety issue: No ]
    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 [ Time Frame: -210 minutes to +100 minutes ] [ Designated as safety issue: No ]
    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 [ Time Frame: -60 minute, +15 minute , + 45 minute, +100 minute ] [ Designated as safety issue: No ]
    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 [ Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes ] [ Designated as safety issue: No ]
    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 [ Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: -60 minutes, +15 minutes, +45 minutes, +100 minutes ] [ Designated as safety issue: No ]
    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 [ Time Frame: -15 minutes, 0 minutes, +15 minutes, +45 minutes ] [ Designated as safety issue: No ]

    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 [ Time Frame: -15 minutes, 0 minutes, +15 minutes, +45 minutes ] [ Designated as safety issue: No ]

    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 [ Time Frame: -90 minutes, +15 minutes, +100 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: -210 minutes, +100 minutes ] [ Designated as safety issue: No ]
    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.


Enrollment: 65
Study Start Date: October 2012
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neurexan®
0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes
Drug: Neurexan®
0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes
Other Name: Neurexan®
No Intervention: No intervention
no tablet intake and subjects will undergo the natural course

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

Ages Eligible for Study:   31 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01703832

Locations
Germany
Institut fur Medizinische Psychologie und Verhaltensimmunbiologie Universitatsklinikum Essen
Essen, Germany, 45122
Klinische Psychologie und Psychotherapie, Fachbereich Psychologie, Universität Marburg
Marburg, Germany, 35032
Sponsors and Collaborators
Biologische Heilmittel Heel GmbH
Investigators
Principal Investigator: Manfred Schedlowski, PhD Institut für Medizinische und Verhaltensimmunbiologie Universitätsklinikum Essen
  More Information

Publications:

Responsible Party: Biologische Heilmittel Heel GmbH
ClinicalTrials.gov Identifier: NCT01703832     History of Changes
Other Study ID Numbers: C1202, 2012-002359-40
Study First Received: October 8, 2012
Results First Received: August 1, 2014
Last Updated: February 9, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission
Germany: Regierungspräsidium Karlsruhe

Keywords provided by Biologische Heilmittel Heel GmbH:
acute stress reaction
stress
stress perception
physiological stress response
Neurexan

Additional relevant MeSH terms:
Fractures, Stress
Stress Disorders, Traumatic, Acute
Anxiety Disorders
Fractures, Bone
Mental Disorders
Stress Disorders, Traumatic
Wounds and Injuries

ClinicalTrials.gov processed this record on April 30, 2015