Post-biotic Intervention for Acute Stress Management (PIAS)

The study aims to evaluate the sub-chronic effects of colonic delivery of a post-biotic 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 post-biotic, when released in the colonic intestinal site, leads to a blunted subjective and objective stress response after a stress induction.

Study Overview

• Status: Completed
• Conditions: Sleep; Stress Response; Cognition; Mood State
• Intervention / Treatment: Other: Placebo; Dietary supplement: Post-biotic (Colonic-Delivery capsule); Dietary supplement: Post-biotic (Regular Administration capsule)

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 post-biotic 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 Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 117597
    • Human Development Research Centre, SICS, A*STAR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
Experimental: Post-biotic, colonic delivery; n=25, 250mg post-biotic once daily in a polymer coated vegan gelatine capsule (colonic delivery)	Other: Placebo; 250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule; Dietary supplement: Post-biotic (Colonic-Delivery capsule); 250mg post-biotic once daily in a polymer coated vegan gelatine capsule (colonic delivery)
Active Comparator: Post-biotic, regular administration; n=25, 250mg post-biotic once daily in a regular uncoated vegan gelatine capsule	Other: Placebo; 250mg Maltodextrin once daily in a regular uncoated vegan gelatine capsule; Dietary supplement: Post-biotic (Regular Administration capsule); 250mg post-biotic once daily in a regular uncoated vegan gelatine capsule

What is the study measuring?

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 smart-watch.	Days 1-7
Sleep Activity	During sleep, the activity will be monitored via a smart-watch throughout the sleep session.	Days 1-7

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ecological Momentary Assessments (EMA)	Subjects are asked to indicate their current state on a visual analogue scale ranging from 'not at all' to 'very much' using a slider.	Day 1-6 (4/day), Day 7 (2/day), Day 8 (1/day)
Salivary α-amylase	α-amylase levels, as a marker of autonomic nervous system activation	Day 7 (5/day)
Gastrointestinal Symptoms	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.	Days 1-7 (1/day)
Speech Analysis for digital stress biomarkers	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.	Day 7 (2/day)
Eye Movement Analysis for digital stress biomarkers	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.	Day 7 (2/day)
Facial Expression Analysis for digital stress biomarkers	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.	Day 7 (2/day)
Handwriting Analysis for digital stress biomarkers	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.	Day 7 (2/day)
Cognitive performance	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.	Days 1-8
Respiratory Rate	Measured as how many breaths per minute. Continuous monitoring via a smart-watch.	Days 1-7
Electrodermal Activity (EDA)	4 user-initiated 2 min sessions per day. Measured via a smart-watch and the total score per session is provided by the watch.	Days 1-7

Collaborators and Investigators

• Sponsor: Institute for Human Development and Potential (IHDP), Singapore
• Investigators: Principal Investigator: Jeroen Schmitt, PhD, Singapore Institute of Clinical Sciences (SICS), A*STAR

Publications and helpful links

General Publications

• Boets E, Gomand SV, Deroover L, Preston T, Vermeulen K, De Preter V, Hamer HM, Van den Mooter G, De Vuyst L, Courtin CM, Annaert P, Delcour JA, Verbeke KA. Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study. J Physiol. 2017 Jan 15;595(2):541-555. doi: 10.1113/JP272613. Epub 2016 Sep 18.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Actual): June 14, 2024
• Study Completion (Actual): June 14, 2024

Study Registration Dates

• First Submitted: October 13, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 24, 2023

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Sleep; Cognition; stress response; Mood State; gut-brain-axis
• Other Study ID Numbers: 2023-086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No