Clinical trial NCT04314011: Clinical Study of Umbilical Cord Mesenchymal Stem Cells Infusion for Aging Frailty
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Study of Umbilical Cord Mesenchymal Stem Cells Infusion for Aging Frailty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Aging Frailty
Lead sponsor: Shanghai East Hospital
Sponsor class: OTHER
First posted: 2020-03-18
Enrollment: 30
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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?

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety of HUC-MSCs infusion
timeFrame: Within one month post infusion
Secondary outcomes:
measure: Difference in rate of decline of Frailty
timeFrame: Baseline, month 1, 3 month and 6 months post infusion
measure: Difference in subject quality of life assessments
timeFrame: Baseline, month 1, month 3 and month 6 post infusion
measure: Changes in the pro-inflammatory cytokines of blood sample between the HUC-MSC and placebo cohorts
timeFrame: Baseline, month 1, month 3 and month 6 post infusion
measure: Changes in cellular components of the immune system between the HUC-MSC and placebo cohorts
timeFrame: Baseline, month 1, month 3 and month 6 post infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital, Shanghai Tongji University
Study officials:
affiliation: Shanghai East Hospital, Shanghai Tongji University
name: Zhongming Liu, MD/Ph.D
role: PRINCIPAL_INVESTIGATOR
References: