Mesenchymal Stem Cells for Age-Related Frailty (MESCAFY)

February 2, 2023 updated by: VA Office of Research and Development

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030-4211
        • Michael E. DeBakey VA Medical Center, Houston, TX

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years to 85 years (OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Group 1
Peripheral IV Infusion of 100 million MSCs at baseline and repeated at three months
Drug: Mesenchymal Stem Cells (MSCs)
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.
EXPERIMENTAL: Group 2
Peripheral IV Infusion of 100 million MSCs at baseline and peripheral IV infusion of placebo at three months
Drug: Mesenchymal Stem Cells (MSCs)
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.
PLACEBO_COMPARATOR: Group 3
Peripheral IV infusion of placebo at baseline and repeated at three months
Drug: Mesenchymal Stem Cells (MSCs)
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adherence
Time Frame: Through study completion at 6 months
Percent of study visits attended
Through study completion at 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Recruitment
Time Frame: Through study completion at 6 months
Number of participants recruited
Through study completion at 6 months
Modified Physical Performance Test
Time Frame: Change from baseline to 6 months
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
Change from baseline to 6 months
6-Minute Walk Test
Time Frame: Change from baseline to 6 months
A performance based measure of functional exercise capacity.
Change from baseline to 6 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
4-minute walk gait speed
Time Frame: Change from baseline to 6 months
Time needed to walk 4 meters at the usual pace will be measured
Change from baseline to 6 months
Activities of daily living (ADL) and instrumental ADL
Time Frame: Change from baseline to 6 months
Assessed using the physical function subscale of the Functional Status Questionnaire
Change from baseline to 6 months
High-Sensitivity C-reactive protein
Time Frame: Change from baseline to 6 months
Marker of chronic inflammation - measured by immunoturbidimetric assay
Change from baseline to 6 months
Knee extensor strength
Time Frame: Change from baseline to 6 months
as evaluated using a Biodex System 3 dynamometer
Change from baseline to 6 months
Soluble tumor necrosis factor receptor 1 (sTNF)
Time Frame: Change from baseline to 6 months
Measured in serum using enzyme-linked immunoabsorbent assay
Change from baseline to 6 months
Interleukin-6
Time Frame: Change from baseline to 6 months
Measured in serum using enzyme-linked immunoabsorbent assay
Change from baseline to 6 months
Bone mineral density of the lumbar spine and hip
Time Frame: Change from baseline to 6 months
Measured using dual-energy x-ray absorptiometry
Change from baseline to 6 months
Lean body mass
Time Frame: Change from baseline to 6 months
Measured by dual-energy x-ray absorptiometry
Change from baseline to 6 months
Visceral fat mass
Time Frame: Change from baseline to 6 months
Measured by dual-energy x-ray absorptiometry (DXA)
Change from baseline to 6 months
Bone microarchitecture
Time Frame: Change from baseline to 6 months
Measured by High-resolution peripheral computed tomography (HR-pQCT) at wrist and distal radius
Change from baseline to 6 months
Bone strength
Time Frame: Change from baseline to 6 months
Measured using micro-finite element analyses of HR-pQCT
Change from baseline to 6 months
Trabecular bone score
Time Frame: Change from baseline to 6 months
A textual parameter that provides an index of trabecular microarchitecture
Change from baseline to 6 months
Cognition
Time Frame: Change from baseline to 6 months
Using the Composite Age-Adjusted Scale Score from the National Institute of Health Toolbox Cognition Battery.
Change from baseline to 6 months
Quality of Life
Time Frame: Change from baseline to 6 months
Using the Physical a nd Mental component subscale of the Medical Outcomes Study SF-36
Change from baseline to 6 months
Body fat
Time Frame: Change from baseline to 6 months
Measured using dual-energy x-ray absorptiometry
Change from baseline to 6 months
Grip strength
Time Frame: Change from baseline to 6 months
Evaluated with a Jamar Handheld dynamometer
Change from baseline to 6 months
Adverse Events
Time Frame: Through study completion at 6 months
Number of non-serious and serious adverse events
Through study completion at 6 months
Short Physical Performance Battery
Time Frame: Change from baseline to 6 months
Objective assessment tool for evaluating lower extremity function
Change from baseline to 6 months
Lipoprotein levels
Time Frame: Change from baseline to 6 months
Measured using automated enzymatic/colorimetric assays
Change from baseline to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VA Office of Research and Development

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Baylor College of Medicine
Michael E. DeBakey VA Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 31, 2023

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2023

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2022

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 17, 2022

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 6, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E4096-P

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD 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).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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