Clinical Trial: Explorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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 stress
Sponsor: Biologische Heilmittel Heel GmbH

Current Primary Outcome:

  • 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.
  • 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.


Original Primary Outcome:

  • Area under the curve (AUC) of VAS tension values [ Time Frame: -210 minutes to +100 minutes ]
  • Area under the curve (AUC) of VAS nervousness values [ Time Frame: -210 minutes to +100 minutes ]


Current Secondary Outcome:

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

  • 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.

  • 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.
  • Psychological Questionnaire (Modified Somatic SCL90) [ Time Frame: -210 minutes, +100 minutes ]
    The SCL90 has

    Original Secondary Outcome:

    • Changes in tension and nervousness VAS [ Time Frame: -180 minutes, -150 minutes, -120 minutes, -90 minutes, -60 minutes, -30 minutes, -15 minutes, 0 minutes, +15 minutes, +30 minutes, +45 minutes, +60 minutes, +75 minutes, +100 minutes ]
    • Changes in saliva cortisol and α-amylase [ Time Frame: -60 minutes, -15 minutes, +15 minutes, +30 minutes, +45 minutes, +60 minutes, +100 minutes ]
    • Changes in plasma ACTH, catecholamines, norepinephrine (NE) and epinephrine (E) [ Time Frame: -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 ]
    • Changes in BP, heart rate and HRV [ Time Frame: -30 minutes, -15 minutes, 0 minutes, +15 minutes, +30 minutes, +45 minutes ]
    • State anxiety and stress perception measured by STAI-X1 [ Time Frame: -90 minutes, +15 minutes ]
    • Incidence of Adverse Events [ Time Frame: -180 minutes to +100 minutes ]


    Information By: Biologische Heilmittel Heel GmbH

    Dates:
    Date Received: October 8, 2012
    Date Started: October 2012
    Date Completion:
    Last Updated: February 9, 2015
    Last Verified: February 2015