Clinical Study of Umbilical Cord Mesenchymal Stem Cells Infusion for Aging Frailty

Study Overview
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Brief Summary
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The purpose of this clinical study is to answer the questions: Is the proposed intervention safe? Is the proposed intervention effective in improving the healthy status of subjects with aging frailty?

Detailed Description
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Aging frailty is a clinical syndrome, characterized by a decrease of homeostatic reserves and enhanced vulnerability to endogenous or exogenous stressors, exposing individuals to an increased risk of adverse health-related outcomes. The human umbilical cord (HUC) is a promising source of mesenchymal stem cells (MSCs), compared to embryonic stem cells, HUC-MSCs are noncontroversial with a painless collection procedure and faster self-renewal properties. HUC-MSCs can differentiate into the different germ layers and modulate immune responses. One possible mechanism for the onset and development of aging frailty is the depletion of stem cells. Hence, intravenous infusion of HUC-MSCs is attractive therapy against aging frailty. This is a randomized, double-blind, placebo-controlled clinical trial. The participants (n = 30) will be randomly distributed into two groups. The HUC-MSCs Group (n = 15) will receive intravenous infusion of mesenchymal stem cells twice over a month (30 days interval), the Control Group (n = 15) will receive the same protocolized intervention with normal saline. Follow-up duration is 6 months after first intervention. The reported serious adverse events（SAEs）will be observed within one month post infusion. The short-item from health survey（SF-36), EuroQol five dimensions questionnaire (EQ-5D) and Fried phenotype scale will be evaluated. Short physical performance battery (SPPB) and plasm biomarkers will be assessed.The assessments will be performed at baseline, 1 month, 3 months and 6 months. The intent of this study is to explore domains of efficacy of HUC-MSCs through the reduction of signs and symptoms of aging frailty and to evaluate the safety of HUC-MSCs in subjects with aging frailty.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Study of Umbilical Cord Mesenchymal Stem Cells Infusion for Aging Frailty

Conditions
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Aging Frailty

Intervention / Treatment
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* Biological: Human umbilical cord mesenchymal stem cells（HUC-MSCs）
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects age ≥60 and ≤80 years at the time of signing the informed consent form. Must show signs of frailty apart from a concomitant condition as assessed by the investigator with a frailty score of 1 to 4 using the Fried Phenotype Scale. Must provide written informed consent. Subjects are expected to live more than 12 months. Exclusion Criteria: 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 Advanced liver or renal failure, class III/IV congestive heart failure, myocardial infarction, unstable angina, cardiac revascularization, or severe obstructive ventilator defect. Uncontrolled hypertension or hyperglycemia. Have known allergies to biological drugs or antibiotics. Expecting to receive organ transplantation. Have a clinical history of malignancy or active autoimmune diseases. Have a history of drug or alcohol abuse within the past 24 months. Be serum-positive for HIV, hepatitis BsAg or viremic hepatitis C. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HUC-MSCs Group<br>Human umbilical cord mesenchymal stem cells (1*10^6/kg cells): delivered via peripheral intravenous infusion. | Biological: Human umbilical cord mesenchymal stem cells（HUC-MSCs）<br>* Human umbilical cord mesenchymal stem cells（HUC-MSCs）<br>|
| Placebo Comparator: Control Group<br>Placebo:normal saline delivered via peripheral intravenous infusion. | Biological: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of HUC-MSCs infusion | Safety were assessed by incidence of reported serious adverse events (SAEs) within one month after infusion. An SAE is defined as any untoward medical occurrence that: Results in death Is life-threatening (stroke or non-fatal pulmonary embolism, etc.) Requires inpatients hospitalization or prolongation of hospitalization Results in clinically significant abnormal laboratory test results or abnormal vital signs, based on clinical judgment. | Within one month post infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in rate of decline of Frailty | Difference in rate of decline of Frailty assessed using Fried phenotype scale: Slowing of Mobility (assessed via a 4-meter gait speed test; Timed up and go (TUG) test and Short Physical Performance Battery (SPPB) assessment) Weight Loss (assessed via weighing scale) Reduced Activity (assessed via Minnesota Leisure Time Activities (MLTA) questionnaire) Diminished handgrip strength (assessed via dynamometer) Exhaustion (assessed by two items from the Center for Epidemiological Studies-Depression, CES-D): I felt that everything I did was an effort? and I could not get going. | Baseline, month 1, 3 month and 6 months post infusion | 
| Difference in subject quality of life assessments | Health-related quality of life will be assessed via Short-Form 36 Health Survey (SF-36), including physical functioning scale and mental health index; the health status including Health State Index (HSI) and respondent's self-rated health on a vertical scale will be accessed via EuroQol 5-Dimension (ED-5D). | Baseline, month 1, month 3 and month 6 post infusion | 
| Changes in the pro-inflammatory cytokines of blood sample between the HUC-MSC and placebo cohorts | Enzyme-linked immunosorbent assay will be used to identify the serum levels of pro-inflammatory cytokines (e.g.,Interleukin-6). | Baseline, month 1, month 3 and month 6 post infusion | 
| Changes in cellular components of the immune system between the HUC-MSC and placebo cohorts | Flow cytometry will be used to identify the changes in numbers of lymphocyte subpopulations (e.g., B cells, T cells). | Baseline, month 1, month 3 and month 6 post infusion |