Microbiome-Targeted Enhancement of Neurocognition With Probiotics-Riboflavin Combination (MENTOR)

Microbiome-Targeted Enhancement of Neurocognition With Probiotics-Riboflavin Combination (MENTOR)

This randomized, double-blind, placebo-controlled trial will evaluate whether 12 weeks of supplementation with the probiotic Lactobacillus rhamnosus GG combined with colon-delivered riboflavin will improve cognitive performance and brain physiology in older adults with memory complaints. The study will assess changes in cognitive outcomes together with neurophysiological markers to explore potential gut-brain axis mechanisms. Through its rigorous design, the trial will aim to determine whether targeted modulation of the intestinal environment can support brain function and cognitive health in aging.

Study Overview

• Status: Not yet recruiting
• Conditions: Cognitive Deficits, Mild
• Intervention / Treatment: Dietary supplement: Experimental 1; Dietary supplement: Experimental 2

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sergej Ostojic, MD, PhD; Phone Number: +381112643242; Email: sergej.ostojic@chess.edu.rs

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age > 65 years
• MoCA scores 18-25 points
• BMI of 20.0 - 29.9 kg/m2 at screening
• Stable body weight (≤ 5% change) over the past 3-months
• Willing to avoid consuming gut microbiome-modulating dietary supplements within 4 weeks prior to the baseline visit
• Subjects will abstain from vitamin B2-rich food intake as per pre-defined list
• Maintain current level of physical activity
• Be willing and able to comply with trial protocol

Exclusion Criteria:

• Severe chronic disease and acute injuries
• History of dietary supplement use four weeks before enrolment
• Organic gastrointestinal (GI) disorders
• Bowel surgery or short bowel syndrome
• Gut-altering medications two months before enrolment
• Is currently using systemic steroids, proton pump inhibitors, H2 blocker, antacid
• History of drug and/or alcohol abuse at the time of enrolment
• Smoker or vaper
• Has made any major dietary changes in the past 3 months prior to baseline
• Has a currently active eating disorder
• Has food allergies or other issues with foods

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental 1; 2 capsules of probiotic and riboflavin cellulose per day	Dietary supplement: Experimental 1; Probiotic and riboflabin
Placebo Comparator: Experimental 2; 2 capsules of microcrystaline cellulose per day	Dietary supplement: Experimental 2; Microcrystaline cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assesment scores	The Montreal Cognitive Assessment (MoCA) score is a brief, 30-point screening measure of global cognitive function. It assesses multiple domains, including memory, attention, executive function, language, visuospatial abilities, and orientation. Higher scores indicate better cognitive performance, with a score of 26 or above generally considered within the normal range, while lower scores suggest varying degrees of cognitive impairment.	Change from baseline The Montreal Cognitive Assessment (MoCA) score at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-Mental State Examination Score	The Mini-Mental State Examination score quantifies global cognitive function by assessing orientation, memory, attention, language, and visuospatial abilities, offering a validated measure for detecting cognitive decline in older adults.	Change from baseline Mini-Mental State Examination Score at 12 weeks
Pittsburgh Sleep Quality Index (PSQI)	The Pittsburgh Sleep Quality Index (PSQI) is a self-report tool used to assess sleep quality and disturbances. It consists of 19 items covering seven components: sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, daytime dysfunction, and use of sleep medications. Each component is scored from 0 to 3, with higher scores indicating worse sleep quality. The total score ranges from 0 to 21, where a score of 5 or higher suggests poor sleep quality. The PSQI is widely used in clinical and research settings to evaluate sleep health.	Change from baseline PSQI at 12 weeks
Brain oxygen saturation	Concentration of hemoglobin index in prefrontal brain	Change from baseline hemoglobin index at 12 weeks
Grip strength	Muscular strength generated by one's forearm muscles	Change from baseline grip strength at 12 weeks

Collaborators and Investigators

• Sponsor: Center for Health Sciences, Serbia
• Investigators: Principal Investigator: Nikola Todorovic, PhD, Center for Mitochondrial Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): August 15, 2027

Study Registration Dates

• First Submitted: February 7, 2026
• First Submitted That Met QC Criteria: February 7, 2026
• First Posted (Actual): February 13, 2026

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 7, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Cognition; Sleep quality; Oxygenation; Bioenergetics
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Neurocognitive Disorders; Sleep Wake Disorders; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Sleep Disorders, Intrinsic; Dyssomnias; Hemic and Lymphatic Diseases; Sleep Initiation and Maintenance Disorders; Lymphoma, Follicular; Cognition Disorders
• Other Study ID Numbers: 11-385-28-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data obtained through this study may be provided to qualified researchers with academic interest in nutritional science. Data will be coded, with no PHI included. Approval of the request and execution of all applicable agreements are prerequisites to the sharing of data with the requesting party.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• IPD Sharing Access Criteria: Only qualified researchers with academic interest in nutritional science.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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