PIAS: Postbiotic Intervention for Acute Stress Management

Sponsor

Singapore Institute for Clinical Sciences (Other)

Overall Status

Recruiting

CT.gov ID

NCT06097182

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

6.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stress Response Mood State Sleep Cognition	Dietary Supplement: Postbiotic (Colonic-Delivery capsule) Dietary Supplement: Postbiotic (Regular Administration capsule) Other: Placebo	N/A

Detailed Description

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Postbiotic Intervention for Acute Stress Management

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Postbiotic, colonic delivery

n=25, 250mg postbiotic once daily in a polymer coated vegan gelatine capsule (colonic delivery)

Dietary Supplement: Postbiotic (Colonic-Delivery capsule)

250mg postbiotic once daily in a polymer coated vegan gelatine capsule (colonic delivery)

Other: Placebo

250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule

Active Comparator: Postbiotic, regular administration

n=25, 250mg postbiotic once daily in a regular uncoated vegan gelatine capsule

Dietary Supplement: Postbiotic (Regular Administration capsule)

250mg postbiotic once daily in a regular uncoated vegan gelatine capsule

Other: Placebo

250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule

Placebo Comparator: Placebo

n=25, 250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule

Other: Placebo

250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule

Outcome Measures

Primary Outcome Measures

Salivary Cortisol [Day 7 (5/day)]
cortisol levels, as a marker of hypothalamic-pituitary-adrenal (HPA) axis activation

Secondary Outcome Measures

State Trait Anxiety Inventory (STAI-6) [Day 7 (2/day)]
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).
The Brunel Mood Scale (BRUMS) [Day 7 (2/day)]
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).
Heart Rate [Days 1-7]
Measured as beats per minute. Continuous monitoring via a smartwatch.
Sleep Activity [Days 1-7]
During sleep, the activity will be monitored via a smartwatch throughout the sleep session.

Other Outcome Measures

Ecological Momentary Assessments (EMA) [Day 1-6 (4/day), Day 7 (2/day), Day 8 (1/day)]
Subjects are asked to indicate their current state on a visual analogue scale ranging from 'not at all' to 'very much' using a slider.
Salivary α-amylase [Day 7 (5/day)]
α-amylase levels, as a marker of autonomic nervous system activation
Gastrointestinal Symptoms [Days 1-7 (1/day)]
Participants will be asked to rate the average severity of the following five symptoms over the preceding 24 hours on a 5-point scale from 0 (absent) to 4 (very severe): bloating/distension, passage of gas, rumbling, feeling of fullness and abdominal discomfort/pain. A daily total score is calculated by summing all items recorded each day. A lower score is concomitant with lower severity of symptoms.
Respiratory Rate [Days 1-7]
Measured as how many breaths per minute. Continuous monitoring via a smartwatch.
Electrodermal Activity (EDA) [Days 1-7]
4 user-initiated 2 min sessions per day. Measured via a smartwatch and the total score per session is provided by the watch.
Speech Analysis for digital stress biomarkers [Day 7 (2/day)]
Subjects are requested to verbally reproduce an orally presented standard short story from Newcomer Story Set. A high-resolution video with audio will be recorded and exploratory analyses of speech characteristics will be performed.
Eye Movement Analysis for digital stress biomarkers [Day 7 (2/day)]
Subjects are requested to verbally reproduce an orally presented standard short story from Newcomer Story Set. A high-resolution video with audio will be recorded and exploratory analyses of eye movements will be performed.
Facial Expression Analysis for digital stress biomarkers [Day 7 (2/day)]
Subjects are requested to verbally reproduce an orally presented standard short story from the Newcomer Story Set. A high-resolution video with audio will be recorded and exploratory analyses of facial characteristics will be performed.
Handwriting Analysis for digital stress biomarkers [Day 7 (2/day)]
Subjects are requested to write down words of a specific category with a specified starting letter. As an exploratory outcome, a digital picture of the written text will be analyzed for handwriting characteristics such as trace, calibre, slant, and distance.
Cognitive performance [Days 1-8]
Cognitive performance will be assessed with a short (5 min) test battery consisting of tests of processing speed, spatial memory, and reaction time delivered through a mobile application that was developed to assess individuals' cognition in natural, non-laboratory, settings.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 30 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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.