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Stress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03494725
Recruitment Status : Completed
First Posted : April 11, 2018
Last Update Posted : November 7, 2018
Sponsor:
Collaborator:
DuPont Nutrition and Health
Information provided by (Responsible Party):
Juliane Hellhammer, Daacro

Brief Summary:
The aim of this study is to assess whether a 5 week intake of a probiotic (Lpc-37) can modulate stress and anxiety experienced by healthy subjects during and after an acute stressor compared to placebo. To measure stress and anxiety, markers of the hypothalamic-pituitary-adrenal (HPA) axis activity and questionnaires will be assessed before, during and after the Trier Social Stress Test (TSST). The results of this study indicate if the chosen study design is suitable to discover stress-related effects of probiotics.

Condition or disease Intervention/treatment Phase
Healthy Stress, Psychological Dietary Supplement: Lpc-37 Dietary Supplement: Placebo Not Applicable

Detailed Description:

The total mass of microorganisms residing within the human intestine is approximately the same as that of the human brain. Of late, these >1000 species and >7000 strains have been described as the "brain in our belly" because of the essential role they play in physiological and psychological health and disease. The gut-brain axis describes the bidirectional communication that exists between the brain and the gut and the microbiota-gut-brain axis supports the role of the gut microbiome in this communication system. Emotional and routine daily life stress can disrupt digestive function, but increasing evidence indicates that the gut microbiota exert a profound influence on brain physiology, psychological responses and ultimately behavior.

A plethora of literature to date, albeit majoritively preclinical, have demonstrated evidence to support the role of the gut microbiome in regulating stress-related changes in physiology, behavior and brain function.

Stress is an individual process to deal with external and internal challenges that ranges from behavioral to molecular adaptations. The HPA axis and its release of stress hormones plays a major role in stress adaptation.

The purpose of this clinical trial is to determine whether a single strain of bacteria derived from the species Lactobacillus paracasei (Lpc-37) can modulate stress experienced by healthy subjects exposed to the TSST measured by HPA axis activation markers and self-report questionnaires.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Proof-of-Concept "Stress & Anxiety Dampening Effects of Lpc-37"
Actual Study Start Date : April 10, 2018
Actual Primary Completion Date : October 9, 2018
Actual Study Completion Date : October 9, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Active Comparator: Lpc-37

Lactobacillus paracasei Lpc-37

1x 1 capsule in the morning for 5 weeks

Dietary Supplement: Lpc-37
Lactobacillus paracasei Lpc-37 at 1 x 10^10 colony forming units (CFU) per day, Microcrystalline cellulose, Magnesium stearate, silicon dioxide

Placebo Comparator: Placebo

Placebo capsule manufactured to mimic Lpc-37 capsule

1x 1 capsule in the morning for 5 weeks

Dietary Supplement: Placebo
Microcrystalline cellulose, Magnesium stearate, silicon dioxide




Primary Outcome Measures :
  1. Change of the HR in response to the TSST [ Time Frame: Continuous measurement starting 20 minutes before the TSST and ending 20 minutes after the TSST after 5 weeks of product intake. ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of the heart rate (HR) in response to the TSST compared to placebo.


Secondary Outcome Measures :
  1. Changes in pre and post treatment STAI-state scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of State-Trait-Anxiety-Inventory (STAI)-state scores compared to placebo.

  2. Changes in pre and post treatment PSS scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of Perceived Stress Scale (PSS) scores compared to placebo.

  3. Changes in pre and post treatment DASS depression scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) depression scores compared to placebo.

  4. Changes in pre and post treatment DASS anxiety scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of DASS anxiety scores compared to placebo.

  5. Changes in pre and post treatment DASS stress scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of DASS stress scores compared to placebo.

  6. Changes in pre and post treatment BAI scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of Beck Anxiety Inventory (BAI) scores compared to placebo.

  7. Changes in pre and post treatment VAS stress perception scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of Visual Analog Scale (VAS) stress perception scores compared to placebo.

  8. Changes in pre and post treatment VAS anxiety scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of VAS anxiety scores compared to placebo.

  9. Changes in pre and post treatment VAS insecurity scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of VAS insecurity scores compared to placebo.

  10. Changes in pre and post treatment VAS exhaustion scores [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of VAS exhaustion scores compared to placebo.

  11. Changes in pre and post treatment systolic BP [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of systolic blood pressure (BP).

  12. Changes in pre and post treatment diastolic BP [ Time Frame: Before and after 5 weeks of study product intake. ]
    Efficacy of the intake of Lpc-37 on the reduction of diastolic BP.

  13. Change of STAI-state scores in response to the TSST [ Time Frame: 10 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of STAI-state scores in response to the TSST compared to placebo.

  14. Change of systolic BP in response to the TSST [ Time Frame: 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of the systolic BP in response to the TSST compared to placebo.

  15. Change of diastolic BP in response to the TSST [ Time Frame: 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of the diastolic BP in response to the TSST compared to placebo.

  16. Change of VAS stress perception scores in response to the TSST [ Time Frame: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of VAS stress perception scores in response to the TSST compared to placebo.

  17. Change of VAS anxiety scores in response to the TSST [ Time Frame: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of VAS anxiety scores in response to the TSST compared to placebo.

  18. Change of VAS insecurity scores in response to the TSST [ Time Frame: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of VAS insecurity scores in response to the TSST compared to placebo.

  19. Change of VAS exhaustion scores in response to the TSST [ Time Frame: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of VAS exhaustion scores in response to the TSST compared to placebo.

  20. Change of salivary cortisol in response to the TSST [ Time Frame: 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of salivary cortisol in response to the TSST compared to placebo.

  21. Change of sAA in response to the TSST [ Time Frame: 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake ]
    Efficacy of the intake of Lpc-37 on reduction of the increase of salivary Alpha-Amylase (sAA) in response to the TSST compared to placebo.

  22. Change of sleep duration over the course of the treatment [ Time Frame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake ]
    Efficacy of the intake of Lpc-37 on the increase of sleep duration over the course of the treatment

  23. Change of sleep related recovery scores over the course of the treatment [ Time Frame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake ]
    Efficacy of the intake of Lpc-37 on the increase of sleep related recovery scores over the course of the treatment

  24. Change of reported number of sleep disruptions over the course of the treatment [ Time Frame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake ]
    Efficacy of the intake of Lpc-37 on the decrease of reported number of sleep disruptions over the course of the treatment

  25. Change of perceived health status scores over the course of the treatment [ Time Frame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake ]
    Efficacy of the intake of Lpc-37 on the increase of perceived health status scores over the course of the treatment

  26. Change of mood scale scores over the course of the treatment [ Time Frame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake ]
    Efficacy of the intake of Lpc-37 on the increase of mood scale scores over the course of the treatment

  27. Change of perceived productivity scores over the course of the treatment [ Time Frame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake ]
    Efficacy of the intake of Lpc-37 on the increase of perceived productivity scores over the course of the treatment

  28. Change of the difference of CAR AUCg measures before and after treatment [ Time Frame: 3 and 2 days before first product intake and 2 and 1 day before last product intake ]
    Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol Awakening Response (CAR) area under the curve with respect to the ground (AUCg) values to the respective mean before and after 5 weeks of treatment

  29. Change of the difference of CAR AUCi measures before and after treatment [ Time Frame: 3 and 2 days before first product intake and 2 and 1 day before last product intake ]
    Efficacy of the intake of Lpc-37 on the reduction of the difference of CAR area under the curve with respect to the increase (AUCi) values to the respective mean before and after 5 weeks of treatment

  30. Change of the difference of CAR total increase measures before and after treatment [ Time Frame: 3 and 2 days before first product intake and 2 and 1 day before last product intake ]
    Efficacy of the intake of Lpc-37 on the reduction of the difference of CAR total increase values to the respective mean before and after 5 weeks of treatment



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Voluntary, written, informed consent to participate in the study
  • Male or female aged between 18-45 years (inclusive)
  • Body mass index (BMI) between 18.5 - 29.9 kg/m2
  • Medical examination at baseline indicates they are healthy in the opinion of the investigator
  • Ability of the participant (in the Principal Investigator's opinion) to comprehend the full nature and purpose of the study including possible risks and side effects
  • Agreement to comply with the protocol and study restrictions
  • Available for all study visits
  • Females of child-bearing potential required to provide a negative urine pregnancy test and to use contraceptives
  • Easy access to internet

Exclusion Criteria:

  • Self-reported diagnosis of one or more Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV axis 1 disorder(s), including but not limited to current major depression, anxiety disorder, bipolar spectrum disorder or schizophrenia
  • Have a significant acute or chronic coexisting illness (cardiovascular, gastrointestinal (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD)), immunological, metabolic, neurodevelopmental or any condition which contraindicates, in the Investigator's judgement, entry to the study
  • Currently taking (from day of screening onwards) or have previously taken (last 4 weeks prior to screening) psychoactive medication (anxiolytics, sedatives, hypnotics, anti-psychotics, anti-depressants, anti-convulsants, centrally acting corticosteroids, opioid pain relievers)
  • Currently taking (from day of screening onwards) medication or dietary supplements that the Investigator believes would interfere with the objectives of the study, pose a safety risk or confound the interpretation of the study results (e.g. melatonin, omega-3 dietary supplements, non-steroidal anti-inflammatory drugs (NSAIDS), over-the-counter (OTC) sleep medication (not categorized as sedatives, hypnotics or anti-depressants), anti-coagulants, proton pump inhibitors, anti-histamines, pseudoephedrine, cortisone, beta-blockers)
  • Recent (within last 4 weeks prior to screening) or ongoing antibiotic therapy during the intervention period
  • Daily consumption of concentrated sources of probiotics and/or prebiotics within 2 weeks of screening and throughout the intervention period other than the provided study products (e.g., probiotic/prebiotic tablets, capsules, drops or powders)
  • Pregnant or lactating female, or pregnancy planned during intervention period
  • Not fluent in German
  • Have self-reported dyslexia
  • History of alcohol, drug, or medication abuse
  • Self-declared illicit drug users (including cannabis and cocaine) for 3 weeks prior to screening and during the intervention period
  • Contraindication to any substance in the investigational product
  • Hypertension (systolic ≥ 140 mmHg, diastolic ≥ 90 mmHg)
  • Known hyper- or hypothyroidism unless treated and under control (stable for more than 3 months)
  • Subjects having previously participated in the TSST
  • Smoking > 5 cigarettes/day
  • Employee of the sponsor or contract research organization (CRO)
  • Participation in another study with any investigational product within 60 days of screening and during the intervention period
  • Investigator believes that the participant may be uncooperative and/or noncompliant and should therefore not participate in the study
  • Participant under administrative or legal supervision

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03494725


Locations
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Germany
daacro GmbH & Co. KG
Trier, Rhineland-Palatinate, Germany, 54296
Sponsors and Collaborators
Daacro
DuPont Nutrition and Health

Additional Information:
Publications:
Dallman, M. F., & Hellhammer, D. (2011). Regulation of the hypothalamo-pituitaryadrenal axis, chronic stress, and energy: the role of brain networks. The handbook of stress science: Biology, psychology, and health, 11-36.
Nishida, K., Sawada, D., Kuwano, Y., Tanaka, H., Sugawara, T., Aoki, Y., ... & Rokutan, K. (2017). Daily administration of paraprobiotic lactobacillus gasseri cp2305 ameliorates chronic stress-associated symptoms in Japanese medical students. Journal of Functional Foods, 36, 112-121.

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Responsible Party: Juliane Hellhammer, PhD, Daacro
ClinicalTrials.gov Identifier: NCT03494725     History of Changes
Other Study ID Numbers: DU01-2017
First Posted: April 11, 2018    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Juliane Hellhammer, Daacro:
Probiotic
Gut-brain axis
Stress
Anxiety

Additional relevant MeSH terms:
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Stress, Psychological
Behavioral Symptoms