Clinical Trial: Neuronal Correlates of Neurexan® Action in Mildly to Moderately Stressed Probands

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

Official Title: Neuronal Correlates of Neurexan® Action in Mildly to Moderately Stressed Probands - A Randomized, Placebo-controlled, Double-blind, Cross-over Trial of Mode of Action and Response Prediction by F

Brief Summary: The purpose of this study is to explore the effect of Neurexan® on the brain response when participants undergo an emotional stressful condition in verum compared to placebo.

Detailed Summary: A randomized placebo-controlled, double-blind, two-period crossover study with an explorative design. 40 healthy males aged 31-59 years will be included in the study. Participant allocation to either Neurexan® or Placebo at study start is randomized with a ratio of 1:1, i.e. 20 Neurexan® first to 20 Placebo first individuals. Participants receive totally three tablets of either Neurexan® or Placebo per treatment period orally.
Sponsor: Biologische Heilmittel Heel GmbH

Current Primary Outcome:

  • Reduced amygdala responsiveness measured by negative face to form contrasts in the Hariri task (Hariri et. al., 2000; Hariri et. al., 2003) after verum versus placebo condition [ Time Frame: Day 1 and Day 2 ]
    Primary Outcome 1: Effect of drug, driven by significantly smaller amygdala activations in the contrast (negative faces vs forms) in verum compared to placebo conditions. Significance level is 0.05, corrected for multiple comparisons in the search volume which is anatomically defined by the AAL (Automated Anatomical Labelling Atlas) coordinates.
  • Reduced functional connectivity density (FCD) in amygdala after verum versus placebo condition during rest. [ Time Frame: Day 1 and Day 2 ]
    Primary Outcome 2: Interaction of time and drug, driven by significantly greater reductions of amygdala functional connectivity density (FCD) in verum compared to placebo conditions. Significance level is 0.05, corrected for multiple comparisons in the search volume which is anatomically defined by the AAL (Automated Anatomical Labelling Atlas) coordinates.
  • Reduced whole brain functional connectivity of amygdala after verum versus placebo condition during rest. [ Time Frame: Day 1 and Day 2 ]
    Primary Outcome 3: Interaction of time and drug, driven by significantly greater changes (smaller and greater, two sided effects because of inclusion of top down and bottom up processes in different regions) of amygdala seeded connectivities in verum compared to placebo conditions. Significance level is 0.05, corrected for multiple comparisons in the whole brain.
  • Reduced local resting state activity of amygdala afte

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Normalized EEG frontal frequency changes associated with normalized HRV in verum relative to placebo conditions. [ Time Frame: Day 1 and Day 2 ]
    • High morning cortisol and alpha-amylase level predicts increased subjective stress response (VAS, STAI-XI), effect which is reversed in verum but not in placebo condition. [ Time Frame: Day 1 and Day 2 ]
      Individual cortisol and alpha-amylase level at 8 timepoints during the MRI visits, VAS (tensions and nervousness) at 7 timepoints, and STAI-X1 at 6 timepoints will be computed as the area under the curve. The relation between change in cortisol, VAS (tension and nervousness) and personality traits (TCI), coping to stress (ABI, FKK), self-esteem (Rosenberg Self-Esteem), and childhood traumatic experiences (CTQ) will be investigated by the use of non-parametric correlations analysis. Changes in subject reported outcome instruments and stress response by morning cortisol and alpha amylase will be evaluated within the framework of formal crossover analyses. Due to unknown distributions, the analysis will be of nonparametric nature.
    • Reduced subjects stress perception as assessed with STAI-XI, VAS after MIST task in verum relative to placebo condition. [ Time Frame: Day 1 and Day 2 ]
      The analysis is already described under point "Outcome 8" and "Outcome 10" of secondary outcome measures.
    • Personality traits assessed with TCI predicted stress response. [ Time Frame: Screening Visit ]
      It will be investigated how personality traits (TCI), anxiety level (STAI), depressive symptoms (BDI-II), self-esteem, subject's coping strategies as well as cognitive processes predict stress response and the relation with Neurexan® efficiency. Regression analyses will be conducted on resting state functional connectivity in placebo and verum conditions. These exploratory analyses are hypothesis generating in order to confine follow up investigations.


    Original Secondary Outcome: Same as current

    Information By: Biologische Heilmittel Heel GmbH

    Dates:
    Date Received: October 28, 2015
    Date Started: August 2015
    Date Completion:
    Last Updated: January 27, 2016
    Last Verified: January 2016