Clinical trial NCT03494725: Stress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects
Official title: Proof-of-Concept "Stress & Anxiety Dampening Effects of Lpc-37"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Stress, Psychological
Keywords: Probiotic
Gut-brain axis
Stress
Anxiety
Lead sponsor: Daacro
Sponsor class: NETWORK
Collaborators: name: DuPont Nutrition and Health
First posted: 2018-04-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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 predominantly 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 Lacticaseibacillus paracasei Lpc-37 (Lpc-37), formerly 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.

Eligibility 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

Primary outcomes:
measure: Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST)
timeFrame: Continuous measurement starting 20 minutes before and ending 20 minutes after the TSST after 5 weeks of product intake. Mean values were calculated per group at seven-time windows before, during and after the TSST
Secondary outcomes:
measure: Changes in Pre and Post Treatment STAI-state Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment Perceived Stress Scale (PSS) Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment DASS Depression Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment DASS Anxiety Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment DASS Stress Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment BAI Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment VAS Stress Perception Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment VAS Anxiety Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment VAS Insecurity Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment VAS Exhaustion Scores
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment Systolic BP
timeFrame: Before and after 5 weeks of study product intake.
measure: Changes in Pre and Post Treatment Diastolic BP
timeFrame: Before and after 5 weeks of study product intake.
measure: Change of STAI-State Scores in Response to the TSST
timeFrame: 10 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake
measure: Change of Systolic BP in Response to the TSST
timeFrame: 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake
measure: Change of Diastolic Blood Pressure (BP) in Response to the TSST
timeFrame: 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake
measure: Change of VAS Stress Perception Scores in Response to the TSST
timeFrame: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake
measure: Change of VAS Anxiety Scores in Response to the TSST
timeFrame: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake
measure: Change of VAS Insecurity Scores in Response to the TSST
timeFrame: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake
measure: Change of VAS Exhaustion Scores in Response to the TSST
timeFrame: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake
measure: Change of Salivary Cortisol in Response to the TSST
timeFrame: 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake
measure: Change of sAA in Response to the TSST
timeFrame: 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake
measure: Change of Sleep Duration Over the Course of the Treatment
timeFrame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
measure: Change of Sleep Related Recovery Scores Over the Course of the Treatment
timeFrame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
measure: Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total)
timeFrame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
measure: Change of Reported Number of Sleep Disruptions Over the Course of the Treatment
timeFrame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
measure: Change of Perceived Health Status Scores Over the Course of the Treatment
timeFrame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
measure: Change of Mood Scale Scores Over the Course of the Treatment
timeFrame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
measure: Change of Perceived Productivity Scores Over the Course of the Treatment
timeFrame: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake
measure: The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures
timeFrame: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)
measure: The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures
timeFrame: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)
measure: The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures
timeFrame: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)
measure: The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures
timeFrame: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake
Other outcomes:
Locations:
city: Trier
country: Germany
facility: daacro GmbH & Co. KG
state: Rhineland-Palatinate
Study officials:
affiliation: Daacro GmbH & Co. KG
name: Juliane Hellhammer, PhD
role: PRINCIPAL_INVESTIGATOR
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