Clinical trial NCT02602275: Neuronal Correlates of Neurexan® Action in Mildly to Moderately Stressed Probands
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 Functional Magnetic Resonance Imaging MRI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Stress Reaction
Keywords: Stress, amygdala, functional MRI, Hariri paradigm, TSST
Lead sponsor: Biologische Heilmittel Heel GmbH
Sponsor class: INDUSTRY
First posted: 2015-11-11
Enrollment: 53
Sex: MALE
Minimum age (years): 31
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 description: 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.

Eligibility criteria: Inclusion Criteria:

1. Male
2. Age between ≥31 to ≤59 years
3. Fluent in German language
4. Nonsmoker
5. Able to understand the explanations and instructions given by the study physician
6. Willing to adhere to the prohibitions and restrictions specified in this protocol
7. Healthy on the basis of clinical laboratory tests, physical examination, medical history, vital signs performed at Screening Visit
8. Magnetic Resonance Imaging (MRI) compatible
9. Participants must have signed a written informed consent document prior to any study procedure indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study
10. Screening Scale for Chronic Stress of the Trier Inventory for Chronic Stress (TICS-SSCS) Score ≥ 9 and ≤ 36
11. Perceived Stress Scale (PSS) \> 9

Exclusion Criteria:

1. Current or past history of psychotic features or a diagnosis of any psychiatric disorder as defined in the Diagnostic and Statistical Manual of Mental Disorder 4th edition (DSM-IV) Axis I (recurrent major depression, panic disorder, social phobia, obsessive-compulsory disorder; alcohol dependency; schizophrenia and mania)
2. History of depressive episodes during the last 3 months prior to Screening Visit
3. Use of any psychotropic medication or suffering from severe psychiatric illness during the last 3 months prior to Screening Visit
4. Intake of prescription drugs for sleeping disorders or nervousness within one month prior to Screening Visit
5. Intake of over the counter (OTC) medication for the treatment of sleeping disorders or nervousness within the last (one) week prior to Screening Visit
6. High chronic stress as verified with the TICS-SSCS (\> 36)
7. Low chronic stress as verified with the TICS-SSCS (\< 9) and PSS ≤ 9
8. Participants with Blood Pressure (BP) ≥ 160/100 on day 0 and at randomization
9. Participants with treated hypertension
10. Known allergies and/or hypersensitivity to ingredients of Neurexan® (Passiflora incarnata, Avena sativa, Coffea arabica, Zincum isovalerianicum, lactose monohydrate, magnesium stearate) or Placebo (Lactose monohydrate, magnesium stearate)
11. Known Lactose intolerance
12. Use of any psychological stress-management intervention within the last 4 weeks prior to Screening Visit
13. History of substance, drug, including nicotine, or alcohol abuse within the preceding 3 months prior to Screening Visit
14. Alcohol, drug, nicotine intake within the last 24 hours before day 0 and at randomization - confirmed by positive screening tests
15. Body Mass Index (BMI) \> 30 kg/m2
16. Works regularly nights shifts
17. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic or hematologic disease as defined by clinical screening interview
18. Any somatic disease or other condition the Investigator or their duly assigned representatives believes could affect the ability of the individual to complete the study or the interpretation of the study results
19. Participants with medical illness that may have influenced brain morphology and/or physiology (e.g. uncontrolled hypertension, diabetes)
20. Participants with a history of one or more seizures without a clear and resolved aetiology
21. Participants with claustrophobia
22. Participants with tinnitus
23. Clinically significant acute illness within 7 days prior to randomization
24. Presence of metallic (ferromagnetic) implants (heart pacemaker, aneurysm clips), tattoos or piercings
25. Have received an experimental drug or used an experimental medical device (participation in any other clinical trial) within the last 30 days before study inclusion
26. Participants whose ability to speak for themselves lacks or can be doubted

Primary outcomes:
measure: Functional Magnetic Resonance Imaging (fMRI) Task Data: BOLD Activation Changes Within Amygdala During Negative Faces in the Hariri Face Matching Task Between Placebo and Neurexan Treatment
timeFrame: 1 hour after taking a single dose of Neurexan or placebo
measure: Functional Magnetic Resonance Imaging (fMRI) Resting-State Data: Change in Global Functional Connectivity Density of the Amygdala at Rest
timeFrame: 1 hour after taking a single dose of Neurexan or placebo
measure: Functional Magnetic Resonance Imaging (fMRI) Resting-State Data: Change in Whole-Brain Functional Connectivity of the Amygdala at Rest
timeFrame: 1 hour after taking a single dose of Neurexan or placebo
measure: Functional Magnetic Resonance Imaging (fMRI) Resting-State Data: Baseline Activity of the Amygdala at Rest as Measured by Amplitude of Low-Frequency Fluctuations (ALFF)
timeFrame: 1 hour after taking a single dose of Neurexan or placebo
measure: Functional Magnetic Resonance Imaging (fMRI) Task Data: Stress Network Activation in Response to Psychosocial Stress Induction.
timeFrame: 1.5 hours after taking a single dose of Neurexan or placebo
Secondary outcomes:
Other outcomes:
Locations:
city: Magdeburg
country: Germany
facility: Clinical Affective Neuroimaging Laboratory (CANLAB)
Study officials:
affiliation: Clinical Affective Neuroimaging Laboratory, Univ. Magdeburg, Germany
name: Martin Walter, PD Dr Med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Herrmann L, Vicheva P, Kasties V, Danyeli LV, Szycik GR, Denzel D, Fan Y, Meer JV, Vester JC, Eskoetter H, Schultz M, Walter M. fMRI Revealed Reduced Amygdala Activation after Nx4 in Mildly to Moderately Stressed Healthy Volunteers in a Randomized, Placebo-Controlled, Cross-Over Trial. Sci Rep. 2020 Mar 2;10(1):3802. doi: 10.1038/s41598-020-60392-w.
citation: Chand T, Alizadeh S, Jamalabadi H, Herrmann L, Krylova M, Surova G, van der Meer J, Wagner G, Engert V, Walter M. EEG revealed improved vigilance regulation after stress exposure under Nx4 - A randomized, placebo-controlled, double-blind, cross-over trial. IBRO Neurosci Rep. 2021 Sep 25;11:175-182. doi: 10.1016/j.ibneur.2021.09.002. eCollection 2021 Dec.
citation: Mayer K, Krylova M, Alizadeh S, Jamalabadi H, van der Meer J, Vester JC, Naschold B, Schultz M, Walter M. Nx4 Reduced Susceptibility to Distraction in an Attention Modulation Task. Front Psychiatry. 2021 Nov 29;12:746215. doi: 10.3389/fpsyt.2021.746215. eCollection 2021.
citation: Chand T, Alizadeh S, Li M, Fan Y, Jamalabadi H, Danyeli L, Nanni-Zepeda M, Herrmann L, Van der Meer J, Vester JC, Schultz M, Naschold B, Walter M. Nx4 Modulated Resting-State Functional Connectivity Between Amygdala and Prefrontal Cortex in a Placebo-Controlled, Crossover Trial. Brain Connect. 2022 Nov;12(9):812-822. doi: 10.1089/brain.2021.0189. Epub 2022 Jun 10.
citation: Nanni-Zepeda M, Alizadeh S, Chand T, Kasties V, Fan Y, van der Meer J, Herrmann L, Vester JC, Schulz M, Naschold B, Walter M. Trait anxiety is related to Nx4's efficacy on stress-induced changes in amygdala-centered resting state functional connectivity: a placebo-controlled cross-over trial in mildly to moderately stressed healthy volunteers. BMC Neurosci. 2022 Nov 24;23(1):68. doi: 10.1186/s12868-022-00754-4.
citation: Herrmann L, Kasties V, Boden C, Li M, Fan Y, Van der Meer J, Vester JC, Seilheimer B, Schultz M, Alizadeh S, Walter M. Nx4 attenuated stress-induced activity of the anterior cingulate cortex-A post-hoc analysis of a randomized placebo-controlled crossover trial. Hum Psychopharmacol. 2022 Sep;37(5):e2837. doi: 10.1002/hup.2837. Epub 2022 Feb 25.
citation: Krylova M, Alizadeh S, Izyurov I, Teckentrup V, Chang C, van der Meer J, Erb M, Kroemer N, Koenig T, Walter M, Jamalabadi H. Evidence for modulation of EEG microstate sequence by vigilance level. Neuroimage. 2021 Jan 1;224:117393. doi: 10.1016/j.neuroimage.2020.117393. Epub 2020 Sep 21.