Mesenchymal Stem/Stromal Cell Therapy in the Treatment of Frailty
Primary Purpose
Frailty
Status
Recruiting
Phase
Phase 1
Locations
Vietnam
Study Type
Interventional
Intervention
Umbilical Cord Mesenchymal Stem Cells transplantation
standard frailty treatment and supplementary medication
Sponsored by
About this trial
This is an interventional treatment trial for Frailty focused on measuring Frailty, umbilical cord mesenchymal stem cells
Eligibility Criteria
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.
Sites / Locations
- Vinmec Research Institute of Stem Cell and Gene TechnologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Treatment (UC-MSC trasnplatation)
control arm
Arm Description
1.5 x 10^6 umbilical Cord Mesenchymal Stem Cells per body kg will transplant via the intravenous at baseline, and the second transplantation will be performed 3 months after the first transplantation and combination with standard frailty treatment and supplementary medication
standard frailty treatment and supplementary medication
Outcomes
Primary Outcome Measures
Adverse events and serious adverse events
To assess safety, the number of AEs or SAEs during stem cell administration (72 h) at 1 months, 3 months, 6 months and 9 months after discharge will be evaluated
Secondary Outcome Measures
Reduced activities
Reduced activities using Community Healthy Activities Model Program for Seniors questionnaire
Slowing of mobility
slowing of mobility using 6-minute walk test
reduction of handgrip strength
reduction of handgrip strength using dynamometer
exhaustion
exhaustion using multidimensional fatigue inventory questionnaire
the level of pain in the knee
the level of pain in the knee using Western Ontario and McMaster Universities Osteoarthritis Index
respiratory function
respiratory function using FEV1/FVC
Quality of Life
Quality of Life using Short Form 36 items
patients' inflammation
information of patients' inflammation response to umbilical cord-derived mesenchymal stem/stromal cells administration
patients' immune
information of patients' immune response to umbilical cord-derived mesenchymal stem/stromal cells administration
immunoregulatory properties of umbilical cord-derived mesenchymal stem/stromal cells
Evaluation of immunoregulatory properties of umbilical cord-derived mesenchymal stem/stromal cells
Cellular senescence
Measurement of cellular senescence using qPCR will be conducted in CD3+ cell population to access the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, a specific biomarker indicated the cellular senescence
metabolic profiles of CD3+ cells
metabolic profiles of CD3+ cells via Seahorse XF Cell Mito Stress Test Kit and Seahorse XF Cell Glycolysis Stress Test Kit (Agilent Technologies)
Full Information
NCT ID
NCT04919135
First Posted
June 2, 2021
Last Updated
April 13, 2023
Sponsor
Vinmec Research Institute of Stem Cell and Gene Technology
1. Study Identification
Unique Protocol Identification Number
NCT04919135
Brief Title
Mesenchymal Stem/Stromal Cell Therapy in the Treatment of Frailty
Official Title
Clinical Study of Mesenchymal Stem/Stromal Cell Therapy in Frailty: a Proposed Experimental Design for Therapeutic and Mechanism Investigation
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 19, 2021 (Actual)
Primary Completion Date
September 20, 2022 (Actual)
Study Completion Date
November 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vinmec Research Institute of Stem Cell and Gene Technology
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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
Detailed Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Frailty
Keywords
Frailty, umbilical cord mesenchymal stem cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (UC-MSC trasnplatation)
Arm Type
Experimental
Arm Description
1.5 x 10^6 umbilical Cord Mesenchymal Stem Cells per body kg will transplant via the intravenous at baseline, and the second transplantation will be performed 3 months after the first transplantation and combination with standard frailty treatment and supplementary medication
Arm Title
control arm
Arm Type
Other
Arm Description
standard frailty treatment and supplementary medication
Intervention Type
Biological
Intervention Name(s)
Umbilical Cord Mesenchymal Stem Cells transplantation
Intervention Description
Patients assigned to UC-MSC administration groups will receive two administrations at a dose of 1.5 million cells/kg patient body weight via the IV route with a 3-month intervening interval
Intervention Type
Drug
Intervention Name(s)
standard frailty treatment and supplementary medication
Intervention Description
Hightamine (Hankook Korus Pharm, Korea), Total calcium (Nugale Pharmaceutical, Canada), Bioflex (Ausbiomed, Australia)
Primary Outcome Measure Information:
Title
Adverse events and serious adverse events
Description
To assess safety, the number of AEs or SAEs during stem cell administration (72 h) at 1 months, 3 months, 6 months and 9 months after discharge will be evaluated
Time Frame
up to the 9-month period following treatment
Secondary Outcome Measure Information:
Title
Reduced activities
Description
Reduced activities using Community Healthy Activities Model Program for Seniors questionnaire
Time Frame
up to the 9-month period following treatment
Title
Slowing of mobility
Description
slowing of mobility using 6-minute walk test
Time Frame
up to the 9-month period following treatment
Title
reduction of handgrip strength
Description
reduction of handgrip strength using dynamometer
Time Frame
up to the 9-month period following treatment
Title
exhaustion
Description
exhaustion using multidimensional fatigue inventory questionnaire
Time Frame
up to the 9-month period following treatment
Title
the level of pain in the knee
Description
the level of pain in the knee using Western Ontario and McMaster Universities Osteoarthritis Index
Time Frame
up to the 9-month period following treatment
Title
respiratory function
Description
respiratory function using FEV1/FVC
Time Frame
up to the 9-month period following treatment
Title
Quality of Life
Description
Quality of Life using Short Form 36 items
Time Frame
up to the 9-month period following treatment
Title
patients' inflammation
Description
information of patients' inflammation response to umbilical cord-derived mesenchymal stem/stromal cells administration
Time Frame
up to the 9-month period following treatment
Title
patients' immune
Description
information of patients' immune response to umbilical cord-derived mesenchymal stem/stromal cells administration
Time Frame
up to the 9-month period following treatment
Title
immunoregulatory properties of umbilical cord-derived mesenchymal stem/stromal cells
Description
Evaluation of immunoregulatory properties of umbilical cord-derived mesenchymal stem/stromal cells
Time Frame
up to the 9-month period following treatment
Title
Cellular senescence
Description
Measurement of cellular senescence using qPCR will be conducted in CD3+ cell population to access the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, a specific biomarker indicated the cellular senescence
Time Frame
up to the 9-month period following treatment
Title
metabolic profiles of CD3+ cells
Description
metabolic profiles of CD3+ cells via Seahorse XF Cell Mito Stress Test Kit and Seahorse XF Cell Glycolysis Stress Test Kit (Agilent Technologies)
Time Frame
up to the 9-month period following treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Liem Thanh Nguyen, Prof
Phone
0986565015
Email
v.liemnt@vinmec.com
First Name & Middle Initial & Last Name or Official Title & Degree
Kien Trung Nguyen, MsC
Phone
0386958552
Email
v.kiennt25@vinmec.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liem Thanh Thanh, Prof
Organizational Affiliation
Vinmec Research Institute of Stem Cell and Gene Technology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vinmec Research Institute of Stem Cell and Gene Technology
City
Hanoi
ZIP/Postal Code
100000
Country
Vietnam
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nguyen Thanh Liem, Prof
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
28977399
Citation
Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, Heldman AW, Miki R, Goldschmidt-Clermont PJ, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Da Fonseca M, Golpanian S, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Green G, Oliva AA, Hare JM. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1513-1522. doi: 10.1093/gerona/glx137.
Results Reference
result
PubMed Identifier
26933813
Citation
Golpanian S, DiFede DL, Pujol MV, Lowery MH, Levis-Dusseau S, Goldstein BJ, Schulman IH, Longsomboon B, Wolf A, Khan A, Heldman AW, Goldschmidt-Clermont PJ, Hare JM. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty. Oncotarget. 2016 Mar 15;7(11):11899-912. doi: 10.18632/oncotarget.7727.
Results Reference
result
PubMed Identifier
34718548
Citation
Hoang DM, Nguyen KT, Hoang VT, Dao LTM, Bui HT, Ho TTK, Nguyen TTP, Ngo ATL, Nguyen HK, Thanh LN. Clinical Study of Mesenchymal Stem/Stromal Cell Therapy for the Treatment of Frailty: A Proposed Experimental Design for Therapeutic and Mechanistic Investigation. J Gerontol A Biol Sci Med Sci. 2022 Jul 5;77(7):1287-1291. doi: 10.1093/gerona/glab326.
Results Reference
derived
Learn more about this trial
Mesenchymal Stem/Stromal Cell Therapy in the Treatment of Frailty
We'll reach out to this number within 24 hrs