Safety and Preliminary Efficacy of Adipose-Derived Stem Cell Secretome in Frailty (VinVital)

Frailty is a common geriatric syndrome characterized by multi-system physiological decline, sarcopenia, and increased vulnerability to stressors. Currently, there are no specific pharmacological treatments for frailty. Preclinical studies have demonstrated that adipose-derived mesenchymal stem cell (AD-MSC) secretome (including extracellular vesicles and soluble growth factors) possesses anti-aging, anti-inflammatory, and regenerative properties, effectively improving physical function and reversing aging phenotypes in aged animal models.

This study aims to investigate the safety and preliminary clinical efficacy of VinVital (oral capsules containing AD-MSC secretome) in older adults with frailty. The trial will enroll 20 eligible patients diagnosed with frailty (Clinical Frailty Scale score 3-6 and meeting modified Fried criteria). Participants will take VinVital (2 capsules/day, equivalent to 4 mg protein/day) for 3 months. Safety and clinical outcomes-including the Short Physical Performance Battery (SPPB), handgrip strength, Clinical Frailty Scale (CFS), Multidimensional Fatigue Inventory (MFI), Pittsburgh Sleep Quality Index (PSQI), and 15D health-related quality of life-will be evaluated at baseline and at months 1, 3, and 6.

• VinVital (Biological): Oral capsules containing adipose-derived mesenchymal stem cell secretome (extracellular vesicles and soluble factors), administered at a dose of 2 capsules per day (total 4 mg protein/day) for 3 months

Primary outcomes

• Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [From the first dose up to 6 months]: Assessment of the safety and tolerability of VinVital based on the occurrence, frequency, and severity of AEs and SAEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 over 6 months.

Secondary outcomes

• Change in Short Physical Performance Battery (SPPB) Score [Baseline, Month 1, Month 3, and Month 6]: Evaluation of physical performance improvement using the SPPB test (including balance, 4-meter walk speed, and 5-times sit-to-stand test) from baseline to months 1, 3, and 6
• Change in Handgrip Strength [Baseline, Month 1, Month 3, and Month 6]: Evaluation of muscle strength changes measured by a digital handgrip dynamometer from baseline to months 1, 3, and 6.
• Change in Clinical Frailty Scale (CFS) Score [Baseline, Month 1, Month 3, and Month 6]: Assessment of the change in frailty severity levels (ranging from 1 to 9) using the Canadian Clinical Frailty Scale from baseline to months 1, 3, and 6
• Change in Multidimensional Fatigue Inventory (MFI) Score [Baseline, Month 1, Month 3, and Month 6]: Evaluation of changes in multidimensional fatigue status using the MFI questionnaire from baseline to months 1, 3, and 6
• Change in Pittsburgh Sleep Quality Index (PSQI) Score [Baseline, Month 1, Month 3, and Month 6]: Assessment of changes in sleep quality and sleep disturbances using the PSQI from baseline to months 1, 3, and 6.
• Change in 15D Health-Related Quality of Life Score [Baseline, Month 1, Month 3, and Month 6]: Evaluation of changes in health-related quality of life across 15 dimensions using the 15D instrument from baseline to months 1, 3, and 6.
• Change in Body Composition (BMI, Lean Mass, Fat Mass, and Bone Mineral Content) [Baseline, Month 1, Month 3, and Month 6]: Evaluation of changes in body composition parameters-including body mass index (BMI), lean body mass, fat mass, and bone mass-measured using a medical-grade body composition analyzer (digital bioimpedance scale) from baseline to months 1, 3, and 6.

Sex: All, ages: 60 Years to 75 Years

Inclusion Criteria:

* Male and female participants aged 60 to 75 years.
* Diagnosed with frailty syndrome meeting the following criteria:

  1. Clinical Frailty Scale (CFS) score between 3 (Managing Well) and 6 (Moderately Frail).
  2. Meeting at least 3 out of 5 modified Fried criteria: (a) Unintentional weight loss, (b) Decreased handgrip strength, (c) Slow walking speed, (d) Low physical activity, (e) Self-reported persistent exhaustion.
* Willing and able to provide written informed consent to participate in the study.

Exclusion Criteria:

* Mini-Mental State Examination (MMSE) score <= 20.
* Currently on an organ transplant waiting list.
* Significant abnormal laboratory values: hemoglobin < 10 g/dL, white blood cell count < 3,000/mm³, platelet count < 120,000/mm³, alkaline phosphatase > 3x ULN, total bilirubin > 1.5 mg/dL.
* Major comorbidities: NYHA class III-IV heart failure, GOLD group C/D chronic obstructive pulmonary disease (COPD), stroke or history of stroke, end-stage renal disease, severe liver disease or active hepatitis (Child-Pugh B/C, acute hepatitis, active chronic hepatitis, or unexplained AST/ALT > 3x ULN), uncontrolled type 2 diabetes mellitus with HbA1c > 8.5%, HIV infection, active acute infection requiring systemic antibiotics, coagulation disorders, or grade 4 knee osteoarthritis.
* Active malignancy within the past 5 years.
* Life expectancy of less than 1 year.
* Symptomatic urinary tract stones requiring intervention.
* Current use of H1 or H2 receptor antagonists.
* History of autoimmune diseases requiring immunosuppressive or biologic therapy.
* Severe malnutrition or limb amputation.
* Chronic gastrointestinal diseases causing malabsorption syndrome.