Explorative Efficacy Profile of Neurexan® in an Experimental Acute Stress Setting in Healthy Subjects

NCT01703819 | Completed Phase 1 Results

• 2 other identifiers: C12012012-002358-22
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the efficacy of acutely dosed Neurexan using an experimental stress test called the Trier Social Stress Test

Conditions

Acute Stress Reaction

Keywords

acute stress reaction; stress; stress perception; physiological stress response; Neurexan

Outcome Measures

Primary Outcomes (2)

• Acute Stress Measured by Tension

  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 Placebo 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.

  -210 minutes to +100 minutes

• Acute Stress Measured by Nervousness

  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 Placebo 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.

  -210 minutes to +100 minutes

Secondary Outcomes (11)

• Changes in Saliva Alpha Amylase

  -60 minutes, +15 minutes, +45 minutes, +100 minutes

• Changes in Saliva Cortisol

  -60 minutes, +15 minutes, +45 minutes, +100 minutes

• Changes in Plasma Adrenocorticotropic Hormone (ACTH)

  -60 minutes, +15 minutes, +45 minutes, +100 minutes

• Changes in Plasma Cortisol

  -60 minutes, +15 minutes, +45 minutes, +100 minutes

• Changes in Plasma Catecholamines (Epinephrine)

  -60 minutes, +15 minutes, +45 minutes, +100 minutes

Study Arms (2)

Neurexan®

EXPERIMENTAL

0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes

Drug: Neurexan®

Placebo

PLACEBO COMPARATOR

6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes

Other: Placebo

Interventions

Neurexan® DRUG

0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes

Neurexan®

Placebo OTHER

6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes

Also known as: Lactose monohydrate, magnesium stearate.

Placebo

Eligibility Criteria

• Age: 31 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent
• Healthy male or female
• age between 31 to 59 years
• Fluent in German language.
• Ability to understand the explanations and instructions given by the study physician

You may not qualify if:

• allergies to ingredients of Neurexan® (Passiflora incarnata, Avena sativa, Coffea arabica, Zincum isovalerianicum, lactose monohydrate, magnesium stearate) or Placebo
• lactose intolerance
• use of any psychological stress-management intervention within the last 4 weeks
• sick leave for any reason
• participation in any other clinical study 3 months prior to Screening Visit
• 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)
• smokers
• alcohol intake within last 24 hours (before Baseline Visit V3)
• shift workers or work regularly during night time
• use of any psychotropic medication or suffering from severe psychiatric illness needing acute intervention
• BMI \> 30 kg/m2
• currently pregnant (verified by urine pregnancy test) or lactating
• participation in a previous TSST study
• 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)
• major mental disorder as verified with the IDCL (depressive episode, panic disorder, social phobia, obsessive-compulsory disorder; alcohol dependency; schizophrenia and mania.)

Sponsors & Collaborators

• Biologische Heilmittel Heel GmbH: lead

Study Sites (2)

Institut fur Medizinische Psychologie und Verhaltensimmunbiologie Universitatsklinikum Essen

Essen, 45122, Germany

Location

Klinische Psychologie und Psychotherapie, Fachbereich Psychologie, Universität Marburg

Marburg, 35032, Germany

Location

Related Publications (11)

• McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007 Jul;87(3):873-904. doi: 10.1152/physrev.00041.2006.

  PMID: 17615391 BACKGROUND

• Elsenbruch S, Lucas A, Holtmann G, Haag S, Gerken G, Riemenschneider N, Langhorst J, Kavelaars A, Heijnen CJ, Schedlowski M. Public speaking stress-induced neuroendocrine responses and circulating immune cell redistribution in irritable bowel syndrome. Am J Gastroenterol. 2006 Oct;101(10):2300-7. doi: 10.1111/j.1572-0241.2006.00837.x. Epub 2006 Sep 4.

  PMID: 16952284 BACKGROUND

• Kirschbaum C, Pirke KM, Hellhammer DH. The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28(1-2):76-81. doi: 10.1159/000119004.

  PMID: 8255414 BACKGROUND

• Hellhammer J, Schubert M. The physiological response to Trier Social Stress Test relates to subjective measures of stress during but not before or after the test. Psychoneuroendocrinology. 2012 Jan;37(1):119-24. doi: 10.1016/j.psyneuen.2011.05.012.

  PMID: 21689890 BACKGROUND

• Schult J, Hero T, Hellhammer J. Effects of powdered fertilized eggs on the stress response. Clin Nutr. 2010 Apr;29(2):255-60. doi: 10.1016/j.clnu.2009.09.004. Epub 2009 Oct 17.

  PMID: 19837490 BACKGROUND

• Mason JW. A review of psychoendocrine research on the pituitary-adrenal cortical system. Psychosom Med. 1968 Sep-Oct;30(5):Suppl:576-607. No abstract available.

  PMID: 4303377 BACKGROUND

• Weiss JM. Somatic effects of predictable and unpredictable shock. Psychosom Med. 1970 Jul-Aug;32(4):397-408. doi: 10.1097/00006842-197007000-00008. No abstract available.

  PMID: 5535207 BACKGROUND

• Pawlak CR, Jacobs R, Mikeska E, Ochsmann S, Lombardi MS, Kavelaars A, Heijnen CJ, Schmidt RE, Schedlowski M. Patients with systemic lupus erythematosus differ from healthy controls in their immunological response to acute psychological stress. Brain Behav Immun. 1999 Dec;13(4):287-302. doi: 10.1006/brbi.1999.0553.

  PMID: 10600217 BACKGROUND

• 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.

  PMID: 8598500 BACKGROUND

• Schmid-Ott G, Jacobs R, Jager B, Klages S, Wolf J, Werfel T, Kapp A, Schurmeyer T, Lamprecht F, Schmidt RE, Schedlowski M. Stress-induced endocrine and immunological changes in psoriasis patients and healthy controls. A preliminary study. Psychother Psychosom. 1998;67(1):37-42. doi: 10.1159/000012257.

  PMID: 9491439 BACKGROUND

• Doering BK, Wegner A, Hadamitzky M, Engler H, Rief W, Schedlowski M. Effects of Neurexan (R) in an experimental acute stress setting--An explorative double-blind study in healthy volunteers. Life Sci. 2016 Feb 1;146:139-47. doi: 10.1016/j.lfs.2015.12.058. Epub 2016 Jan 7.

  PMID: 26772822 DERIVED

MeSH Terms

Conditions

Stress Disorders, Traumatic, Acute

Interventions

neurexan; stearic acid

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Results Point of Contact

• Title: Christine Frank, PhD
• Organization: Biologische Heilmittel Heel GmbH

christine.frank@heel.com

+49 7221 501 3188

Study Officials

• Manfred Schedlowski, PhD

  Institut für Medizinische Psychologie und Verhaltensimmunbiologie Universitätsklinikum Essen

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2012
• First Posted: October 11, 2012
• Study Start: October 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: February 11, 2015
• Results First Posted: February 11, 2015

Record last verified: 2015-02

Locations

DE (2)