Postbiotic Intervention for Acute Stress Management

Study Overview
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Brief Summary
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The study aims to evaluate the sub-chronic effects of colonic delivery of a postbiotic on stress response, mood state, sleep, and cognition in healthy young subjects with elevated self-reported stress levels. It is hypothesized that oral intake of the postbiotic, when released in the colonic intestinal site, leads to a blunted subjective and objective stress response after a stress induction.

Detailed Description
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Scientific findings over the past years suggest that certain bacteria in our gastrointestinal system have an influence on our mood, although, the mechanisms are not yet well understood. One of the possibilities is that bacteria produce compounds that interact with neurons in the gut. These neurons could subsequently send signals to the brain. This study is a proof of principle study examining the effects of a postbiotic in the distal intestinal tract (terminal ileum, colon) on stress response, mood state, sleep, and cognition. The study is expected to provide key insights in the potential of treatment strategies aimed at stimulating the colonic enteric nervous system to exert mood enhancement. It is hypothesized that interactions with the local Enteric Nervous System leading to stress reduction, mood enhancement and sleep promotion effects. The study will employ an in-person clinic visit, in addition to traditional self-reported, behavioural, and physiological outcome measures; exploratory digital health outcomes will also be included to identify novel objective mood/stress measures. This study seeks to recruit a total of 75 healthy males (25 in each arm), between the ages of 21-30 years old (inclusive) from local community outreach in Singapore over a period 12 months. This study is a hybrid study (partially decentralized). The total duration of participation from each participant will be 9 days (excluding, the screening and enrolment days).

Official Title
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Postbiotic Intervention for Acute Stress Management

Conditions
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Stress Response, Mood State, Sleep, Cognition

Intervention / Treatment
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* Dietary Supplement: Postbiotic (Colonic-Delivery capsule)
* Dietary Supplement: Postbiotic (Regular Administration capsule)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 21 to 30 years Men Perceived Stress Scale (PSS-10) score >13 Own and uses a smartphone that is capable to run the study applications with access to the internet Adequate fluency in the English language to understand the inform consent process, study instructions and study assessments Sufficient vision and hearing to complete study procedures Willing to commit to the study procedures Willing and able to participate and to give written informed consent All inclusion criteria will be assessed based on self-reported information during the screening visit. Exclusion Criteria: Past (< 6 months prior to the study) or current major neurological, psychiatric, gastrointestinal, metabolic disease or cardiovascular disease Past (<1 months prior to the study) or current use of psychoactive medication, cardiovascular medication, or corticosteroids. Known medical history of hypotension or currently on antihypertensive medication Alcohol intake >1 units day Present or past history of alcohol or drug addiction and/or recreational drug use BMI <18.5 or >25 kg/m2 Maltodextrin allergy Members of the research team or their immediate family members. An immediate family member is defined as spouse, parent, child, or sibling, whether biological or legally adopted All exclusion criteria will be assessed based on self-reported information during the screening call.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study design: The study will be carried out according to a randomized, placebo-controlled, double-blind, 3 arm parallel-groups design. It will be executed as a hybrid study (partially decentralized). Total study duration is 9 days (day 0 to day 8), excluding screening and enrolment.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Postbiotic, colonic delivery<br>n=25, 250mg postbiotic once daily in a polymer coated vegan gelatine capsule (colonic delivery) | Dietary Supplement: Postbiotic (Colonic-Delivery capsule)<br>* 250mg postbiotic once daily in a polymer coated vegan gelatine capsule (colonic delivery)<br>Other: Placebo<br>* 250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule<br>|
| Active Comparator: Postbiotic, regular administration<br>n=25, 250mg postbiotic once daily in a regular uncoated vegan gelatine capsule | Dietary Supplement: Postbiotic (Regular Administration capsule)<br>* 250mg postbiotic once daily in a regular uncoated vegan gelatine capsule<br>Other: Placebo<br>* 250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule<br>|
| Placebo Comparator: Placebo<br>n=25, 250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule | Other: Placebo<br>* 250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Salivary Cortisol | cortisol levels, as a marker of hypothalamic-pituitary-adrenal (HPA) axis activation | Day 7 (5/day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| State Trait Anxiety Inventory (STAI-6) | The STAI-6 is a validated short-form version (6 items) of the 40-item STAI questionnaire, measuring current anxiety symptoms on a 4-point Likert scale. Total score is calculated (range 6-24). | Day 7 (2/day) | 
| The Brunel Mood Scale (BRUMS) | The BRUMS is a 24-item questionnaire of simple mood descriptors such as angry, nervous, unhappy, and energetic. The BRUMS has six subscales, with each of the subscales containing four mood descriptors. The subscales are anger, confusion, depression, fatigue, tension, and vigour. Responses are recorded using a 5-point Likert scale (0-4). | Day 7 (2/day) | 
| Heart Rate | Measured as beats per minute. Continuous monitoring via a smartwatch. | Days 1-7 | 
| Sleep Activity | During sleep, the activity will be monitored via a smartwatch throughout the sleep session. | Days 1-7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gut-brain-axis, stress response, Cognition, Mood State, Sleep