This trial is to investigate the safety and potential therapeutic efficacy of allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) in combination with standard frailty treatment in Vietnam

Frailty, a specific condition of increased vulnerability and reduced general health associated with aging in elderly people, is an emerging global burden requiring major implications for clinical practice and public health. The lack of standardized definition and treatment of the disease resulted in the increasing number of elders diagnosed with frailty. Recently, preclinical and clinical studies support the safety of mesenchymal stem/stromal cells (MSCs) in the treatment of frailty. However, no comprehensive study has been conducted to access the interrelationship between frailty conditions and the effects of MSC-based therapy. To fill this knowledge gap, the aim of the trial is to investigate the safety and potential therapeutic efficacy of allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) in combination with standard frailty treatment in Vietnam. Moreover, this study describes the rationale, study design, methodologies, and analysis strategy currently employed in stem cell research and clinical study. This randomized case-control phase I/II trial is conducted at Vinmec Times City International Hospital, Hanoi, Vietnam between July 2021 and November 2022. In this trial, 44 patients will be enrolled and randomized into a UC-MSC administration group and control group. Both groups will receive the standard frailty treatment and supplementary medication. The UC-MSC group will receive two doses of thawed UC-MSC product at 1.5x10^6 cells/kg of patient body's weight with an intervention interval of three months. The primary outcome measures will include the incidence of prespecified administration-associated adverse events (AEs) and serious adverse events (SAEs). The potential efficacy will be evaluated based on the improvement in frailty conditions (including physical examination, patient-reported outcomes, quality of life, immune markers of frailty, metabolism analysis, and cytokine markers from patient's plasma). The clinical evaluation will be conducted at baseline and 1-, 3-, 6- and 9-months post-intervention. This clinical trial and stem cell analysis associated with patients' sampling at different timepoints seeks to identify and characterize the potential effects of UC-MSCs on the improvement of frailty based on stem cell quality, cytokines/growth factors secretion profiles of UC-MSCs, cellular senescence, and metabolic analysis of patient's CD3+ cells. The ultimate results of the study will be essential for evaluating the utility of UC-MSC therapy for the treatment of frailty and mechanism underlying these effects providing the fundamental knowledge for designing and implementing research strategy of future studies

Inclusion Criteria:

• Must show signs of frailty apart from a concomitant condition as assessed by the investigator with a frailty score >=3 using the Fried Phenotype Scale.
• They showed the signs of frailty based on physician assessment, apart from a concomitant condition, by a score between 3 and 6 as denoted by the Canadian Study on Health Aging.
• Must provide written informed consent.

Exclusion Criteria:

• Score of less than or equal to 20 on the Mini-Mental State Examination (MMSE)
• Active listing (or expected future listing) for transplant of any organ.
• Clinically important abnormal screening laboratory values, including but not limited to: hemoglobin <8 g/dl, white blood cell count <3000/mm3, platelets<80,000/mm3, alkaline phosphatase > 3 times the upper limit of normal, total bilirubin > 1.5 mg/dl.
• Serious comorbid illness that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study. Including, but not limited to HIV, advanced liver or renal failure, class II/III/IV congestive heart failure, myocardial infarction, unstable angina, or cardiac revascularization within the last six months, or severe obstructive ventilator defect, COPD with GOLD D, ischemic stroke with NIHSS <5, type II diabetes with HbA1C >8.5%
• Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.
• Be an organ transplant recipient.
• Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease-free for 5 years), except curatively treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma if recurrence occurs.
• Have a non-pulmonary condition that limits lifespan to < 1 year.