Exploratory Study on a Multi-nutrient Supplement and Exercise Program for Improving Health Markers Associated to Longevity in Pre-frail Adults (RtM)

A Single-arm Exploratory Study to Investigate the Feasibility to Develop a Composite Score That Encompasses Gut (Microbiome), Muscle, Immune, Cognition Outcomes Based on a 12-weeks Intervention of a Novel Multi-nutrient Supplement Containing Synbiotics, Combined With Supervised Exercise in Pre-frail Individuals Aged 50 - 80 Years Old.

Frailty is associated with biological changes in the gut microbiome and immune system, along with marked declines in physical and cognitive function, leading to an overall reduction in quality of life. Prefrailty represents an early stage where interventions may prevent or reverse these declines. This study aims to evaluate whether a 12-week combined Synbiotic enriched oral nutritional supplement and supervised exercise program can improve muscle strength and mass, gut microbiome composition, immune function, and cognitive performance in prefrail adults aged 50-80 years.

Study Overview

• Status: Recruiting
• Conditions: Aging; Pre-Frailty
• Intervention / Treatment: Behavioral: Supervised exercise program; Dietary supplement: a balanced micronutrient blend

Detailed Description

As we age, biological age, gut microbiome, muscle, immune, and cognition undergo gradual decline. Aging is associated with progressive declines in multiple physiological systems which affects healthspan (years free from diseases). Skeletal muscle undergoes atrophy and functional impairment, characterized by reductions in muscle fiber size and number. Cognitive decline occurs with age and is associated with structural and functional brain changes, contributing to impairments in memory, attention, and executive function. The aging immune system exhibits immuno-senescence, marked by diminished adaptive immune responses, altered T-cell function, and chronic low-grade inflammation. To reduce the healthspan-lifespan gap, Healthy Longevity Medicine (HLM) aims to optimise health and healthspan by targeting the ageing processes across the lifespan. To help mitigate these age-related changes, research is increasingly focused on developing targeted interventions such as nutritional supplements and structured exercise programs. Objective: To explore the effects of a 12-week intervention including supervised exercise and a Synbiotic enriched oral nutritional supplement on gut (microbiome), muscle, immune, cognition and biological age outcomes in pre-frail individuals aged 50-80 years. Study design: This is a single-arm, open-label, interventional, exploratory, single-centre study in which 40 pre-frail male and female individuals aged 50-80 years will be administered a novel multi-nutrient supplement containing synbiotics combined with supervised exercise for a total of 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mazzarine Dotou, PhD; Phone Number: +65 87264704; Email: mazzarine@nus.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore, 117597
    • Recruiting
    • MD11 Clinical Research Centre, #03-01, 10 Medical Drive
    • Principal Investigator: Andrea Britta Maier, MD, PhD, FRACP
    • Contact: Mazzarine Dotou, PhD, MBA; Phone Number: +65 87264704; Email: mazzarine@nus.edu.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Singapore residents of all ethnic groups
2. Adults aged 50-80 years (both male and female)
3. Body mass index (BMI) ≥18 kg/m²
4. Classified as Prefrailty according to Fried frailty criteria
5. Willing and able to attend all data collection visits and to comply with the exercise and supplementation protocols.
6. Able and willing to provide written informed consent.

Exclusion Criteria:

1. Current use of supplements containing: Bifidobacterium longum 536 (BB536) like Kordel's BB536 bifidus; Bifidobacterium longum such as GniiB immunity; GOS (Galacto-oligosaccharides); FOS (Fructo-oligosaccharides); Inulin or any commercial healthy-aging powdered milk products
2. BMI >30 kg/m2 3 Being on special diets including but not limited to ketogenic diets or diets prescribed by a healthcare professional

4. Received any vaccination within the past 8 weeks. 5. Inition of new medication or use of medications affecting gastrointestinal function within the past 8 weeks, including but not limited to antibiotics or Proton pump inhibitors 6. Known allergies or intolerances, including, soy allergy; fibre allergy (e.g., GOS) or requirement for a fibre-free diet; fish allergy; Cow's milk protein allergy or lactose intolerance; galactosaemia 7. More than two unstable chronic conditions (e.g., hypertension, diabetes, hyperlipidemia, osteoarthritis, COPD) 8. Medical conditions for which probiotic use is contraindicated, including but not limited to immunocompromised individuals, astrointestinal failure or severe gastrointestinal disturbances (e.g., blood in stool), presence of a central venous catheter, open wounds following surgery 9. Contraindications to oral feeding, including gastrointestinal failure, complete intestinal obstruction, inability to access the gut or high loss intestinal fistulae 10. Known renal disease were unable to tolerate 2 servings per day. 11. Intake of supplemental calcium >500 mg/day or vitamin D >40 µg/day (1600 IU) from all sources, including diet and supplements 12. Use of medications that may interact with or impair absorption of milk products (e.g., tetracyclines) 13. Any other condition deemed by PI that may compromise participant safety and study compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention Arm; The participants will be administered a powder oral nutritional supplement containing a synbiotic blend of prebiotics and probiotic, a protein blend and a micronutrient blend, combined with supervised exercise for a total of 12 weeks.

Behavioral: Supervised exercise program; A supervised exercise intervention consisting of resistance and endurance training, delivered two times per week, with each session lasting 60 minutes, conducted by an exercise physiologist in the gym's clinic in Singapore.; Dietary supplement: a balanced micronutrient blend; A balanced micronutrient blend containing soral nutritional supplement in powder form containing a synbiotic blend of prebiotics and probiotic, a protein blend and a micronutrient blend provided by Danone Global R&I Center. The participant will be required to take two servings of the study product daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle mass measured via B- mode ultrasound	Change from baseline to Week 12 in muscle mass assessed by muscle thickness measured using B-mode ultrasound. Muscle thickness was measured in centimeters (cm) at a predefined anatomical site	Baseline and 12 weeks
Change on Fecal Bifidobacterium level measured via stool microbiome analysis	Change from baseline at 6 and 12 weeks in stool Bifidobacterium abundance, measured by quantitative PCR (qPCR), and in microbiome diversity, measured by 16S rRNA gene sequencing and shotgun metagenomic sequencing.	Baseline, 6 weeks and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognitive performance National Institutes of Health Toolbox Cognition Battery - Fluid composite	Change from baseline to 12 weeks in cognitive performance assessed by the National Institutes of Health Toolbox Cognition Battery - Fluid composite. [scores of 0 to 100 in raw or age-corrected scaled score]	Baseline and 12 weeks
Change in the immune function (CD4+: CD8+ ratio)	Change from baseline at 6 weeks and 12 weeks in CD4+: CD8+ in T-cell ratio	Baseline, 6 weeks and 12 weeks
Change in cardiorespiratory fitness (Peak VO₂)	Change from baseline to 12 weeks in maximal oxygen uptake (VO₂peak) assessed using standardized cardiopulmonary exercise testing (mL/kg/min)	Baseline and 12 weeks
Change in Muscle Strength assessed using 1RM strength test	Change from baseline to 12 weeks in 1RM strength (Smith machine bench press) (Kg)	Baseline and 12 weeks
Change in Handgrip Strength Measured by Dynamometer	Change from baseline to Week 6 and Week 12 in handgrip strength measured using a calibrated handgrip dynamometer. Grip strength was recorded in kilograms (kg) according to standardized testing procedures.	Baseline, 6 weeks and 12 weeks
Stool consistency, frequency and gastrointestinal tolerance	Stool consistency and frequency will be measured during the study. Gastrointestinal tolerance will be evaluated through participant-reported symptoms.	baseline, 12 weeks
Change in Biological age determined by DNAm clocks	Change from baseline to 12 weeks in biological age derived from DNA methylation profiling	baseline, 12 weeks
Change in advanced glycation end-products (AGEs) assessed using skin autofluorescence.	Change from baseline to 12 weeks in circulating and/or tissue levels of advanced glycation end-products (AGEs), assessed using skin autofluorescence (AU).	Baseline, 12 weeks
Change in inflammatory markers (IL-6, IL-10, TNF-α and IFN-γ)	Change from baseline to Week 6 and Week 12 in serum inflammatory markers including interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). Concentrations were measured in picograms per milliliter (pg/mL) using validated laboratory assay methods.	Baseline, 6 weeks and 12 weeks
Change in immune function as measured by Lymphocyte/neutrophil ratio	Change from baseline to 6 weeks and 12 weeks in Lymphocyte/neutrophil cells ratio	Baseline, 6 weeks and 12 weeks
Change in blood pressure measured using SphygmoCor-XCEL	Change from baseline to Week 6 and Week 12 in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured in millimeters of mercury (mmHg) using the AtCor Medical SphygmoCor XCEL device.	baseline, 6 weeks, 12 weeks
Change in Arterial stiffness measured via SphygmoCor-XCEL	Change from baseline to Week 12 in arterial stiffness assessed using the AtCor Medical SphygmoCor XCEL device. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cfPWV), reported in meters per second (m/s).	Baseline and 12 weeks
Change in Physical Activity Levels Measured by Wearable Devices	Change from baseline to Week 12 in physical activity levels (daily steps) assessed using wearable devices (e.g., OURA ring).	baseline, 12 weeks
Change in heart rate measured with SphygmoCor-XCEL	Change from baseline at 6 weeks and 12 weeks in heart rate (pbm)	Baseline, 6 weeks and 12 weeks
Change in Lean Mass measured by Dual-Energy X-ray Absorptiometry (DXA)	Change from baseline in Lean Mass measured by Dual-Energy X-ray Absorptiometry (DXA)	Baseline and 12 weeks
Change in Body Composition Measured by Bioimpedance (InBody 770)	Change in Body Composition (fat mass and fat-free mass, Kg) measured by Bioimpedance (InBody 770)	Baseline and 12 weeks
Change in Quality of life assessed by The 36-Item Short Form Health Survey questionnaire (SF-36)	Change from baseline to 12 weeks in tThe 36-Item Short Form Health Survey questionnaire (SF-36) [Score ranging from 0 to 100]	baseline, 12 weeks
Change in Quality of Life Measured by EuroQol 5-Dimensions (EQ-5D)	Change from baseline to Week 12 in health-related quality of life as measured by the EuroQol 5-Dimensions (EQ-5D) questionnaire. The EQ-5D assesses five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses are converted to a single EQ-5D index value using a country-specific value set. The EQ-5D index score typically ranges from less than 0 (health states worse than death) to 1.0 (full health).	Baseline, 12 weeks
Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI)	Change from baseline to Week 12 in sleep quality assessed using the validated Pittsburgh Sleep Quality Index (PSQI) questionnaire. Scores range from 0 to 21, with higher scores indicating worse sleep quality.	Baseline and 12 weeks
Change in Sleep Quality Measured by SATED Sleep Questionnaire	Change from baseline to Week 12 in sleep quality assessed using the SATED questionnaire. Scores range from 0 to 24, with higher scores indicating better sleep quality.	Baseline, 12 weeks
Change in Sleep Efficiency Measured by Wearable Device	Change from baseline to Week 12 in sleep efficiency assessed using a wearable device (e.g., OURA ring). Sleep efficiency is reported as a percentage (%), with higher values indicating better sleep quality.	Baseline and Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study participation and retention rates	Participation rate defined as the percentage of eligible participants enrolled, and dropout rate defined as the percentage of participants who discontinue the study and reasons for dropout	12 weeks
Adherence to supplement intervention	Supplement adherence, measured as the proportion (%) and total number of prescribed doses taken, as verified by returned empty sachet counts at each visit.	12 weeks
Adherence to exercise intervention	Adherence to the exercise intervention, assessed as the number and percentage of scheduled exercise sessions attended, as recorded by study staff.	12 weeks

Collaborators and Investigators

• Sponsor: National University of Singapore
• Collaborators: Danone Global Research & Innovation Center
• Investigators: Principal Investigator: Prof. Andrea Britta Maier, MD, PHD, FRACP, National University of Singapore

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2025
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): May 8, 2026

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Gut microbiome; Nutritional supplementation; supervised exercise; Prefrail elderly; Biological age markers
• Other Study ID Numbers: NUS-IRB-2025-418

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the primary, secondary and other outcome measures reported in this study, will be made available on request. Data will be fully de-identified and will not include direct identifiers. Raw data (e.g., DNA methylation, microbiome sequencing) may be shared in processed or aggregated form, as appropriate, to minimize re-identification risk.
• IPD Sharing Time Frame: IPD and supporting information will become available after study completion and publication of the main findings, with the end date to be determined.
• IPD Sharing Access Criteria: Access to de-identified IPD will be provided upon reasonable request to qualified researchers with a methodologically sound proposal and appropriate ethical approval. Requests will be reviewed by the study investigators and data will be shared under a data use agreement specifying permitted uses, data security requirements, and restrictions on re-identification..
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; 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