Psychophysiological Effects of Probiotic Supplementation

Study Overview
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Brief Summary
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This is a pilot exploratory study to investigate the effects of a probiotic Bifidobacterium longum NCC3001 intake on physiological and psychophysiological parameters related to stress in healthy individuals with mild to moderate stress level.

Detailed Description
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The purpose of the study is to explore the effects of a probiotic Bifidobacterium longum NCC3001 intake on physiological and psychophysiological parameters related to stress in healthy individuals with mild to moderate stress level. The objectives is three: Measure the effects of a 6-week supplementation with NCC3001 on psychological and physiological parameters in response to an acute experimental stress; Measure the effects of a 6-week supplementation with NCC3001 on chronic stress level, gastro-intestinal symptoms and sleep quality; Explore changes in the profiles of biological parameters associated with ingestion of NCC3001; including changes in hormones, neurotransmitters, circulating immune and microbiome-derived molecules and changes in the microbiome itself

Official Title
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Effect of 6-week Probiotic Supplementation on Stress-related Parameters in Healthy Adults With Different Levels of Stress

Conditions
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Mild to Moderate Levels of Stress

Intervention / Treatment
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* Dietary Supplement: Experimental probiotic product
* Other: Placebo comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and sign the informed consent Healthy adult men and/or women aged 25 to 65 years old Mild to moderate stress, defined as a score in the range of 15 to 25 on the validated Depression, Anxiety and Stress Scale (DASS-42) Proficiency in French and/or English Normal visual acuity and hearing with or without correction (self-reported) BMI in the range of 18.5 to 29.9 kg/m2 Exclusion Criteria: Diagnosed food allergies Currently participating or having recently participated in a clinical study with products potentially interfering with the results as judged by the investigator Organic gastrointestinal pathology other than benign polyps, diverticulosis, hemorrhoids Chronic or recurrent diarrhea with spontaneous bowel movements more often than 2 times daily Concurrent diagnosed systemic chronic disease (e.g., endocrine, cardiovascular, metabolic, liver, celiac) Willing to avoid the consumption of probiotic-containing products (including yogurts containing probiotics) i.e. any commercially available product specified as containing Lactobacillus, Bifidobacteria, Streptococcus or Saccharomyces for the 2 weeks prior to randomization visit Willing to avoid the use of antibiotics in the 4 weeks prior to randomization visit Adherence to an overly unbalanced diet such as vegan, paleo, ketogenic, low carbohydrate, raw diets Conditions that may affect mood

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Exploratory, randomized, placebo-controlled, 2-arms, double-blinded, parallel
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic NCC3001<br>Sachets of NCC3001 and excipient (maltodextrin) to be administered orally every day for 6 weeks | Dietary Supplement: Experimental probiotic product<br>* Probiotic supplementation<br>|
| Placebo Comparator: Matched Placebo Comparator<br>Sachets of matching placebo containing maltodextrin, yeast extract, cystein HCl and pea flour to be administered orally every day for 6 weeks | Other: Placebo comparator<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Salivary cortisol level | Salivary cortisol levels (nmol/L) before and after stressor | Before the stressor (time-point -20 minutes) and after the stressor (time-point +0 min, time-point +5 min, time-point +10 min, time-point +20 min, time-point +30 min, time-point +40 min) at both baseline and after 6 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortisol level from waking saliva samples | Cortisol level (nmol/L) from waking saliva samples collected 0, 15, 30, 45, 60 min after waking | Baseline and after 6 weeks treatment | 
| Mean heart rate variability | Mean heart rate variability in the time (ms) measured continuously before, during and after the stressor by means of a portable a computer-based data acquisition system from Biopac, Inc | Baseline and after 6 weeks treatment | 
| Heart frequency | Heart frequency (Hz) measured continuously before, during and after the stressor by means of a portable a computer-based data acquisition system from Biopac, Inc | Baseline and after 6 weeks treatment | 
| Mean skin conductance level | Mean skin conductance level (SCL, kΩ) measured continuously before, during and after the stressor by means of a portable a computer-based data acquisition system from Biopac, Inc | Baseline and after 6 weeks treatment | 
| Self-reported measures before and after the stressor (PANAS) | Positive and negative affect scores (1-50) computed with the Positive and Negative Affect Schedule (PANAS) | Baseline and after 6 weeks treatment | 
| Self-reported measures before and after the stressor (STAI-6) | Likert scores (1-4) for 6 mood dimensions: calm, tense, upset, relaxed, content, worry from the State Trait Anxiety Inventory 6-item short form (STAI-6) | Baseline and after 6 weeks treatment | 
| Self-reported measures before, during and after the stressor (VAS) | VAS scores in mm (0-100) for subjective perception of the stress induction | Baseline and after 6 weeks treatment | 
| Self-reported endpoints from standard questionnaires (PSS) | Perceived stress score (0-56) computed from the Perceived Stress Scale (PSS) | Baseline and after 6 weeks treatment | 
| Self-reported endpoints from standard questionnaires (HADs) | Scores (0-21) of depression and anxiety computed from the Hospital Anxiety and Depression scale (HADs) | Baseline and after 6 weeks treatment | 
| Self-reported endpoints from standard questionnaires (GSRS) | Scores from the Gastrointestinal Symptom-Rating Scale (GSRS): scores range from 1 to 7 and higher scores represent more discomfort | Baseline and after 6 weeks treatment | 
| Self-reported endpoints from standard questionnaires (Pittsburgh Sleep Quality) | Sleep quality score from the Pittsburgh Sleep Quality Index questionnaire (score 0-21: the lower, the better sleep quality) | Baseline and after 6 weeks treatment | 
| Probiotic in feces | Probiotic quantity in feces (genome copy number / million 16S copy number) | Baseline and after 6 weeks treatment | 
| Microbiome related metabolites in stool, blood and urine | Microbiome related metabolites in stool, blood and urine | Baseline and after 6 weeks treatment |