Aging, Pre-Frailty
Conditions
Keywords
Prefrail elderly, Gut microbiome, Nutritional supplementation, supervised exercise, Biological age markers
Brief summary
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.
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.
Interventions
BEHAVIORALSupervised 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_SUPPLEMENTa 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.
Sponsors
National University of Singapore
Danone Global Research & Innovation Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
This is an open-label, single-arm, exploratory study in which 40 prefrail participants will receive a 12-week combined of an oral nutritional supplement in powder form containing a synbiotic blend of prebiotics and probiotic, a protein blend and a micronutrient blend and exercise intervention
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in muscle mass measured via B- mode ultrasound | 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 |
| Change on Fecal Bifidobacterium level measured via stool microbiome analysis | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in cognitive performance National Institutes of Health Toolbox Cognition Battery - Fluid composite | 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. \[scores of 0 to 100 in raw or age-corrected scaled score\] |
| Change in the immune function (CD4+: CD8+ ratio) | Baseline, 6 weeks and 12 weeks | Change from baseline at 6 weeks and 12 weeks in CD4+: CD8+ in T-cell ratio |
| Change in cardiorespiratory fitness (Peak VO₂) | Baseline and 12 weeks | Change from baseline to 12 weeks in maximal oxygen uptake (VO₂peak) assessed using standardized cardiopulmonary exercise testing (mL/kg/min) |
| Change in Muscle Strength assessed using 1RM strength test | Baseline and 12 weeks | Change from baseline to 12 weeks in 1RM strength (Smith machine bench press) (Kg) |
| Change in Handgrip Strength Measured by Dynamometer | 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. |
| Stool consistency, frequency and gastrointestinal tolerance | baseline, 12 weeks | Stool consistency and frequency will be measured during the study. Gastrointestinal tolerance will be evaluated through participant-reported symptoms. |
| Change in Biological age determined by DNAm clocks | baseline, 12 weeks | Change from baseline to 12 weeks in biological age derived from DNA methylation profiling |
| Change in advanced glycation end-products (AGEs) assessed using skin autofluorescence. | 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). |
| Change in inflammatory markers (IL-6, IL-10, TNF-α and IFN-γ) | 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. |
| Change in immune function as measured by Lymphocyte/neutrophil ratio | Baseline, 6 weeks and 12 weeks | Change from baseline to 6 weeks and 12 weeks in Lymphocyte/neutrophil cells ratio |
| Change in blood pressure measured using SphygmoCor-XCEL | 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. |
| Change in Arterial stiffness measured via SphygmoCor-XCEL | 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). |
| Change in Physical Activity Levels Measured by Wearable Devices | baseline, 12 weeks | Change from baseline to Week 12 in physical activity levels (daily steps) assessed using wearable devices (e.g., OURA ring). |
| Change in heart rate measured with SphygmoCor-XCEL | Baseline, 6 weeks and 12 weeks | Change from baseline at 6 weeks and 12 weeks in heart rate (pbm) |
| Change in Lean Mass measured by Dual-Energy X-ray Absorptiometry (DXA) | Baseline and 12 weeks | Change from baseline in Lean Mass measured by Dual-Energy X-ray Absorptiometry (DXA) |
| Change in Body Composition Measured by Bioimpedance (InBody 770) | Baseline and 12 weeks | Change in Body Composition (fat mass and fat-free mass, Kg) measured by Bioimpedance (InBody 770) |
| Change in Quality of life assessed by The 36-Item Short Form Health Survey questionnaire (SF-36) | baseline, 12 weeks | Change from baseline to 12 weeks in tThe 36-Item Short Form Health Survey questionnaire (SF-36) \[Score ranging from 0 to 100\] |
| Change in Quality of Life Measured by EuroQol 5-Dimensions (EQ-5D) | 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). |
| Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI) | 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. |
| Change in Sleep Quality Measured by SATED Sleep Questionnaire | 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. |
| Change in Sleep Efficiency Measured by Wearable Device | 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. |
Countries
Singapore
Contacts
CONTACTMazzarine Dotou, PhD
PRINCIPAL_INVESTIGATORProf. Andrea Britta Maier, MD, PHD, FRACP
National University of Singapore
Outcome results
None listed