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Mesenchymal Stem Cells for Age-Related Frailty (MESCAFY)

Primary Purpose

Frailty

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Mesenchymal Stem Cells (MSCs)

About this trial

This is an interventional treatment trial for Frailty focused on measuring Frailty, Aging, Mesenchymal Stem Cells, Physical Function, Cognitive Function, Sarcopenia, Osteoporosis

Eligibility Criteria

65 Years - 85 Years (Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Age 65 - 85 years and living in the community
Modified Physical Performance Test score of 18 to 31
Clinical Frailty Scale score of 5 or 6
6-minute walk distance of >200m and <400m
Willing to provide informed consent

Exclusion Criteria:

Failure to provide informed consent
Major cardiopulmonary disease (e.g., recent MI, unstable angina, stroke) or unstable disease (e.g. NYHA Class II or IV congestive heart failure, severe pulmonary disease requiring steroid pills or the use of supplemental oxygen
Severe neuromuscular disease (e.g., multiple sclerosis, Parkinson's disease, Amyotrophic lateral sclerosis)
Renal impairment as defined by an estimated glomerular filtration rate (eGFR or less than 30 ml/min/1.73 m2)
Other significant co-morbid disease (e.g., severe psychiatric disorder [e.g. bipolar, schizophrenia], excess alcohol use (>14 drinks per week)
Uncontrolled hypertension (BP>160/90 mm Hg)
Significant cognitive impairment, defined as a known diagnosis of dementia or positive screening test for dementia using the Mini-Mental State Exam (i.e., MMSE score <24)
Poorly controlled diabetes (HbA1c >8.5%)
History of malignancy during the past 5 years (except non-melanoma skin cancers)
Have autoimmune disease (e.g., Rheumatoid arthritis, systemic lupus erythematosus)
Be using chronic immunosuppressant therapy such as high-dose corticosteroids or TNF-alpha antagonists (prednisone use at doses of < 5 mg daily is allowed)
Test positive for hepatitis B virus - If the subject tests positive for anti-hepatitis B core antigen (HBc) or anti-HBs, they must be currently receiving treatment for Hepatitis B prior to infusion and remain on treatment throughout the study
Test positive for Hepatitis C virus, HIV1/2, or syphilis
Have any clinically important screening laboratory values, including hemoglobin <10.0 g/dL, WBC <2.500/ul or platelet count<100,000/ul, AST or ALT > 3 times the upper limit of normal, INR>1.3 not due to reversible cause (e.g., warfarin)
Treatment with another investigational drug or other intervention within three months
A history or current evidence of any condition, laboratory abnormality, or other circumstance that might confound the interpretation of the results

Sites / Locations

Michael E. DeBakey VA Medical Center, Houston, TX

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Group 1

Group 2

Group 3

Arm Description

Peripheral IV Infusion of 100 million MSCs at baseline and repeated at three months

Peripheral IV Infusion of 100 million MSCs at baseline and peripheral IV infusion of placebo at three months

Peripheral IV infusion of placebo at baseline and repeated at three months

Outcomes

Primary Outcome Measures

Adherence

Percent of study visits attended

Secondary Outcome Measures

Recruitment

Number of participants recruited

Modified Physical Performance Test

Includes seven standardized tests (walking 15.2 m, putting and removing a coat, picking up a penny, standing up from a chair, lifting a book, climbing one flight of stairs, and progressive romberg test) plus two additional tasks (going up and down four flights of stairs and making a 360-degree turn). Perfect score is 36

6-Minute Walk Test

A performance based measure of functional exercise capacity.

Full Information

NCT ID

NCT05284604

First Posted

March 8, 2022

Last Updated

February 2, 2023

Sponsor

VA Office of Research and Development

Collaborators

Michael E. DeBakey VA Medical Center, Baylor College of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT05284604

Brief Title

Mesenchymal Stem Cells for Age-Related Frailty

Acronym

MESCAFY

Official Title

A Pilot Study of Mesenchymal Stem Cells as Novel Therapy for Age-Related Frailty in Veterans

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Insufficient funding

Study Start Date

January 31, 2023 (Actual)

Primary Completion Date

January 31, 2023 (Actual)

Study Completion Date

January 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

VA Office of Research and Development

Collaborators

Michael E. DeBakey VA Medical Center, Baylor College of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Frailty is a health state related to the aging process in which multiple body systems gradually lose their built-in reserves. It is a medical condition of reduced function in older adults which is associated with increased risks of adverse outcomes such as falls, disability, admission to hospital, or need for long-term care. Currently, there is no specific medical treatment of frailty. Mesenchymal stem cells (MSCs) are undifferentiated cells that self-replicated, and some may change into a particular cell type. These cells go to areas of injury due to signals released by injured cells. Upon reaching, the target tissue, MSCs repair injury by releasing growth factors and immune modulators to assist in the body's repair process. This initial study will assess the practicability of using MSCs for age-related frailty and provide information for planning a future full study of MSCs for maximizing Veteran's functional independence.

Detailed Description

Frailty is an aging-related syndrome of impaired physiologic reserve and function across multiple organs, leading to increased vulnerability for adverse health outcomes. Frailty is associated with an increased risk for falls, disability, hospitalization, and mortality. Given the rapid growth in the aging population, the prevalence of frailty will continue to increase. In fact, Veterans receiving care at Veterans Health Administration are a high risk population for onset of frailty due to being predominantly older associated with a larger proportion of minorities, lower socioeconomic and educational status, higher prevalence of comorbidities, and higher rates of unemployment. Frailty now affects at least 3 of every 10 U.S. Veterans aged 65 years and older and is strongly associated with mortality. It is increasingly being recognized that frailty may be an appropriate target for intervention to reduce disability and dependence in older adults. However, there are no specific medical or biologic treatments that ameliorate or reverse frailty. Conversely, stem cell depletion is a key mechanism for age-related frailty. There is a strong link between frailty, inflammation, and the impaired ability to repair tissue injury due to decreases in endogenous stem cell production. Accordingly, a cell-based, regenerative treatment strategy i.e., allogenic bone-marrow derived mesenchymal stem cell (MSC) therapy may represent a novel therapy for aging frailty. MSCs migrate into the site of injury and home to the affected tissue, where they act to reduce inflammation and promote cellular repair. The advantages of MSCs as a therapeutic strategy for age-related frailty include availability, ease of isolation and expansion, multilineage differentiation and immunosuppression, free from ethical issues, and limited replicative lifespan. In this 6-month pilot study, the investigators will assess 1) the feasibility of MSC therapy in age-related frailty as it relates to functional improvement and 2) develop/refine MSC therapy as a new intervention in older Veterans with frailty, and thus provide preliminary participant response to inform a future trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Frailty

Keywords

Frailty, Aging, Mesenchymal Stem Cells, Physical Function, Cognitive Function, Sarcopenia, Osteoporosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Participants are assigned to one of three groups in parallel for the duration of the study

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

All investigators, study assessors, and participants will not be aware of the group assessments (double-blinded randomized controlled trial)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

Peripheral IV Infusion of 100 million MSCs at baseline and repeated at three months

Arm Title

Group 2

Arm Type

Experimental

Arm Description

Peripheral IV Infusion of 100 million MSCs at baseline and peripheral IV infusion of placebo at three months

Arm Title

Group 3

Arm Type

Placebo Comparator

Arm Description

Peripheral IV infusion of placebo at baseline and repeated at three months

Intervention Type

Drug

Intervention Name(s)

Mesenchymal Stem Cells (MSCs)

Intervention Description

The MSCs are recovered from bone marrows of healthy donors. Each donor is carefully screened for pathogens to assure the product is safe. The MSCs are strictly compliant with FDA standards under Current Good Manufacturing Practice (cGMP) regulations.

Primary Outcome Measure Information:

Title

Adherence

Description

Percent of study visits attended

Time Frame

Through study completion at 6 months

Secondary Outcome Measure Information:

Title

Recruitment

Description

Number of participants recruited

Time Frame

Through study completion at 6 months

Title

Modified Physical Performance Test

Description

Time Frame

Change from baseline to 6 months

Title

6-Minute Walk Test

Description

A performance based measure of functional exercise capacity.

Time Frame

Change from baseline to 6 months

Other Pre-specified Outcome Measures:

Title

4-minute walk gait speed

Description

Time needed to walk 4 meters at the usual pace will be measured

Time Frame

Change from baseline to 6 months

Title

Activities of daily living (ADL) and instrumental ADL

Description

Assessed using the physical function subscale of the Functional Status Questionnaire

Time Frame

Change from baseline to 6 months

Title

High-Sensitivity C-reactive protein

Description

Marker of chronic inflammation - measured by immunoturbidimetric assay

Time Frame

Change from baseline to 6 months

Title

Knee extensor strength

Description

as evaluated using a Biodex System 3 dynamometer

Time Frame

Change from baseline to 6 months

Title

Soluble tumor necrosis factor receptor 1 (sTNF)

Description

Measured in serum using enzyme-linked immunoabsorbent assay

Time Frame

Change from baseline to 6 months

Title

Interleukin-6

Description

Measured in serum using enzyme-linked immunoabsorbent assay

Time Frame

Change from baseline to 6 months

Title

Bone mineral density of the lumbar spine and hip

Description

Measured using dual-energy x-ray absorptiometry

Time Frame

Change from baseline to 6 months

Title

Lean body mass

Description

Measured by dual-energy x-ray absorptiometry

Time Frame

Change from baseline to 6 months

Title

Visceral fat mass

Description

Measured by dual-energy x-ray absorptiometry (DXA)

Time Frame

Change from baseline to 6 months

Title

Bone microarchitecture

Description

Measured by High-resolution peripheral computed tomography (HR-pQCT) at wrist and distal radius

Time Frame

Change from baseline to 6 months

Title

Bone strength

Description

Measured using micro-finite element analyses of HR-pQCT

Time Frame

Change from baseline to 6 months

Title

Trabecular bone score

Description

A textual parameter that provides an index of trabecular microarchitecture

Time Frame

Change from baseline to 6 months

Title

Cognition

Description

Using the Composite Age-Adjusted Scale Score from the National Institute of Health Toolbox Cognition Battery.

Time Frame

Change from baseline to 6 months

Title

Quality of Life

Description

Using the Physical a nd Mental component subscale of the Medical Outcomes Study SF-36

Time Frame

Change from baseline to 6 months

Title

Body fat

Description

Measured using dual-energy x-ray absorptiometry

Time Frame

Change from baseline to 6 months

Title

Grip strength

Description

Evaluated with a Jamar Handheld dynamometer

Time Frame

Change from baseline to 6 months

Title

Adverse Events

Description

Number of non-serious and serious adverse events

Time Frame

Through study completion at 6 months

Title

Short Physical Performance Battery

Description

Objective assessment tool for evaluating lower extremity function

Time Frame

Change from baseline to 6 months

Title

Lipoprotein levels

Description

Measured using automated enzymatic/colorimetric assays

Time Frame

Change from baseline to 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 65 - 85 years and living in the community Modified Physical Performance Test score of 18 to 31 Clinical Frailty Scale score of 5 or 6 6-minute walk distance of >200m and <400m Willing to provide informed consent Exclusion Criteria: Failure to provide informed consent Major cardiopulmonary disease (e.g., recent MI, unstable angina, stroke) or unstable disease (e.g. NYHA Class II or IV congestive heart failure, severe pulmonary disease requiring steroid pills or the use of supplemental oxygen Severe neuromuscular disease (e.g., multiple sclerosis, Parkinson's disease, Amyotrophic lateral sclerosis) Renal impairment as defined by an estimated glomerular filtration rate (eGFR or less than 30 ml/min/1.73 m2) Other significant co-morbid disease (e.g., severe psychiatric disorder [e.g. bipolar, schizophrenia], excess alcohol use (>14 drinks per week) Uncontrolled hypertension (BP>160/90 mm Hg) Significant cognitive impairment, defined as a known diagnosis of dementia or positive screening test for dementia using the Mini-Mental State Exam (i.e., MMSE score <24) Poorly controlled diabetes (HbA1c >8.5%) History of malignancy during the past 5 years (except non-melanoma skin cancers) Have autoimmune disease (e.g., Rheumatoid arthritis, systemic lupus erythematosus) Be using chronic immunosuppressant therapy such as high-dose corticosteroids or TNF-alpha antagonists (prednisone use at doses of < 5 mg daily is allowed) Test positive for hepatitis B virus - If the subject tests positive for anti-hepatitis B core antigen (HBc) or anti-HBs, they must be currently receiving treatment for Hepatitis B prior to infusion and remain on treatment throughout the study Test positive for Hepatitis C virus, HIV1/2, or syphilis Have any clinically important screening laboratory values, including hemoglobin <10.0 g/dL, WBC <2.500/ul or platelet count<100,000/ul, AST or ALT > 3 times the upper limit of normal, INR>1.3 not due to reversible cause (e.g., warfarin) Treatment with another investigational drug or other intervention within three months A history or current evidence of any condition, laboratory abnormality, or other circumstance that might confound the interpretation of the results

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dennis T Villareal, MD

Organizational Affiliation

Michael E. DeBakey VA Medical Center, Houston, TX

Official's Role

Principal Investigator

Facility Information:

Facility Name

Michael E. DeBakey VA Medical Center, Houston, TX

City

Houston

State/Province

Texas

ZIP/Postal Code

77030-4211

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

MEDVAMC will not provide unrestricted, open public access to large scale health related datasets because of re-identification concerns and the obligation to protect Veterans' private information. However, controlled public access will be provided to the greatest extent possible under specific DUAs or other written agreements, and open access will be provided to the final datasets underlying peer-reviewed publications (aggregated data that can be released with privacy and confidentiality risks).

Learn more about this trial

Mesenchymal Stem Cells for Age-Related Frailty

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