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NCT Number: NCT07454616

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

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.

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Key information

Conditions

Pre-Frailty Aging

Age range

50 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

MD11 Clinical Research Centre, #03-01, 10 Medical Drive

Singapore, 117597

Location status: Recruiting

Location contact

Andrea Britta Maier, MD, PhD, FRACP

PRINCIPAL_INVESTIGATOR

Mazzarine Dotou, PhD, MBA

CONTACT

[email protected]

+65 87264704

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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
  • BMI >30 kg/m2 3 Being on special diets including but not limited to ketogenic diets or diets prescribed by a healthcare professional
  • 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.

Treatment and study plan

Supervised exercise program

Behavioral

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.

a balanced micronutrient blend

Dietary Supplement

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.

Primary outcomes

  1. Change in muscle mass measured via B- mode ultrasound

    Time frame: Baseline and 12 weeks

    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

  2. Change on Fecal Bifidobacterium level measured via stool microbiome analysis

    Time frame: Baseline, 6 weeks and 12 weeks

    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.

Secondary outcomes

  1. Change in cognitive performance National Institutes of Health Toolbox Cognition Battery - Fluid composite

    Time frame: Baseline and 12 weeks

    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]

  2. Change in the immune function (CD4+: CD8+ ratio)

    Time frame: Baseline, 6 weeks and 12 weeks

    Change from baseline at 6 weeks and 12 weeks in CD4+: CD8+ in T-cell ratio

  3. Change in cardiorespiratory fitness (Peak VO₂)

    Time frame: Baseline and 12 weeks

    Change from baseline to 12 weeks in maximal oxygen uptake (VO₂peak) assessed using standardized cardiopulmonary exercise testing (mL/kg/min)

  4. Change in Muscle Strength assessed using 1RM strength test

    Time frame: Baseline and 12 weeks

    Change from baseline to 12 weeks in 1RM strength (Smith machine bench press) (Kg)

  5. Change in Handgrip Strength Measured by Dynamometer

    Time frame: Baseline, 6 weeks and 12 weeks

    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.

  6. Stool consistency, frequency and gastrointestinal tolerance

    Time frame: baseline, 12 weeks

    Stool consistency and frequency will be measured during the study. Gastrointestinal tolerance will be evaluated through participant-reported symptoms.

  7. Change in Biological age determined by DNAm clocks

    Time frame: baseline, 12 weeks

    Change from baseline to 12 weeks in biological age derived from DNA methylation profiling

  8. Change in advanced glycation end-products (AGEs) assessed using skin autofluorescence.

    Time frame: Baseline, 12 weeks

    Change from baseline to 12 weeks in circulating and/or tissue levels of advanced glycation end-products (AGEs), assessed using skin autofluorescence (AU).

  9. Change in inflammatory markers (IL-6, IL-10, TNF-α and IFN-γ)

    Time frame: Baseline, 6 weeks and 12 weeks

    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.

  10. Change in immune function as measured by Lymphocyte/neutrophil ratio

    Time frame: Baseline, 6 weeks and 12 weeks

    Change from baseline to 6 weeks and 12 weeks in Lymphocyte/neutrophil cells ratio

  11. Change in blood pressure measured using SphygmoCor-XCEL

    Time frame: baseline, 6 weeks, 12 weeks

    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.

  12. Change in Arterial stiffness measured via SphygmoCor-XCEL

    Time frame: Baseline and 12 weeks

    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).

  13. Change in Physical Activity Levels Measured by Wearable Devices

    Time frame: baseline, 12 weeks

    Change from baseline to Week 12 in physical activity levels (daily steps) assessed using wearable devices (e.g., OURA ring).

  14. Change in heart rate measured with SphygmoCor-XCEL

    Time frame: Baseline, 6 weeks and 12 weeks

    Change from baseline at 6 weeks and 12 weeks in heart rate (pbm)

  15. Change in Lean Mass measured by Dual-Energy X-ray Absorptiometry (DXA)

    Time frame: Baseline and 12 weeks

    Change from baseline in Lean Mass measured by Dual-Energy X-ray Absorptiometry (DXA)

  16. Change in Body Composition Measured by Bioimpedance (InBody 770)

    Time frame: Baseline and 12 weeks

    Change in Body Composition (fat mass and fat-free mass, Kg) measured by Bioimpedance (InBody 770)

  17. Change in Quality of life assessed by The 36-Item Short Form Health Survey questionnaire (SF-36)

    Time frame: baseline, 12 weeks

    Change from baseline to 12 weeks in tThe 36-Item Short Form Health Survey questionnaire (SF-36) [Score ranging from 0 to 100]

  18. Change in Quality of Life Measured by EuroQol 5-Dimensions (EQ-5D)

    Time frame: Baseline, 12 weeks

    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).

  19. Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI)

    Time frame: Baseline and 12 weeks

    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.

  20. Change in Sleep Quality Measured by SATED Sleep Questionnaire

    Time frame: Baseline, 12 weeks

    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.

  21. Change in Sleep Efficiency Measured by Wearable Device

    Time frame: Baseline and Week 12

    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.

Other outcomes

  1. Study participation and retention rates

    Time frame: 12 weeks

    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

  2. Adherence to supplement intervention

    Time frame: 12 weeks

    Supplement adherence, measured as the proportion (%) and total number of prescribed doses taken, as verified by returned empty sachet counts at each visit.

  3. Adherence to exercise intervention

    Time frame: 12 weeks

    Adherence to the exercise intervention, assessed as the number and percentage of scheduled exercise sessions attended, as recorded by study staff.

Study contacts

Contact information is provided by the study sponsor or research team.

Mazzarine Dotou, PhD

CONTACT

[email protected]

+65 87264704

Sponsors and collaborators

Lead sponsor

National University of Singapore

Other

Collaborators

  • Danone Global Research & Innovation Center

Registry information

Official study title

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.

Acronym: RtM

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Mar 6, 2026
Registry last updated
Mar 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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