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

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

The purpose of this clinical study is to answer the questions:

1. Is the proposed intervention safe?
2. Is the proposed intervention effective in improving the healthy status of subjects with aging frailty?

Study Overview

• Status: Completed
• Conditions: Aging Frailty
• Intervention / Treatment: Biological: Placebo; Biological: Human umbilical cord mesenchymal stem cells（HUC-MSCs）

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200120
    • Shanghai East Hospital, Shanghai Tongji University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects age ≥60 and ≤80 years at the time of signing the informed consent form.
2. 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.
3. Must provide written informed consent.
4. Subjects are expected to live more than 12 months.

Exclusion Criteria:

1. 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
2. Advanced liver or renal failure, class III/IV congestive heart failure, myocardial infarction, unstable angina, cardiac revascularization, or severe obstructive ventilator defect.
3. Uncontrolled hypertension or hyperglycemia.
4. Have known allergies to biological drugs or antibiotics.
5. Expecting to receive organ transplantation.
6. Have a clinical history of malignancy or active autoimmune diseases.
7. Have a history of drug or alcohol abuse within the past 24 months.
8. Be serum-positive for HIV, hepatitis BsAg or viremic hepatitis C.
9. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
10. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HUC-MSCs Group; 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）; Human umbilical cord mesenchymal stem cells（HUC-MSCs）
Placebo Comparator: Control Group; Placebo:normal saline delivered via peripheral intravenous infusion.	Biological: Placebo; Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai East Hospital
• Investigators: Principal Investigator: Zhongming Liu, MD/Ph.D, Shanghai East Hospital, Shanghai Tongji University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Frailty
• Other Study ID Numbers: EC.D (BG).020.02.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No