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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT05284604
Other study ID # E4096-P
Secondary ID
Status Withdrawn
Phase Phase 1/Phase 2
First received
Last updated
Start date January 31, 2023
Est. completion date January 31, 2023

Study information

Verified date February 2023
Source VA Office of Research and Development
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date January 31, 2023
Est. primary completion date January 31, 2023
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 65 Years to 85 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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.

Locations

Country Name City State
United States Michael E. DeBakey VA Medical Center, Houston, TX Houston Texas

Sponsors (3)

Lead Sponsor Collaborator
VA Office of Research and Development Baylor College of Medicine, Michael E. DeBakey VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other 4-minute walk gait speed Time needed to walk 4 meters at the usual pace will be measured Change from baseline to 6 months
Other Activities of daily living (ADL) and instrumental ADL Assessed using the physical function subscale of the Functional Status Questionnaire Change from baseline to 6 months
Other High-Sensitivity C-reactive protein Marker of chronic inflammation - measured by immunoturbidimetric assay Change from baseline to 6 months
Other Knee extensor strength as evaluated using a Biodex System 3 dynamometer Change from baseline to 6 months
Other Soluble tumor necrosis factor receptor 1 (sTNF) Measured in serum using enzyme-linked immunoabsorbent assay Change from baseline to 6 months
Other Interleukin-6 Measured in serum using enzyme-linked immunoabsorbent assay Change from baseline to 6 months
Other Bone mineral density of the lumbar spine and hip Measured using dual-energy x-ray absorptiometry Change from baseline to 6 months
Other Lean body mass Measured by dual-energy x-ray absorptiometry Change from baseline to 6 months
Other Visceral fat mass Measured by dual-energy x-ray absorptiometry (DXA) Change from baseline to 6 months
Other Bone microarchitecture Measured by High-resolution peripheral computed tomography (HR-pQCT) at wrist and distal radius Change from baseline to 6 months
Other Bone strength Measured using micro-finite element analyses of HR-pQCT Change from baseline to 6 months
Other Trabecular bone score A textual parameter that provides an index of trabecular microarchitecture Change from baseline to 6 months
Other Cognition Using the Composite Age-Adjusted Scale Score from the National Institute of Health Toolbox Cognition Battery. Change from baseline to 6 months
Other Quality of Life Using the Physical a nd Mental component subscale of the Medical Outcomes Study SF-36 Change from baseline to 6 months
Other Body fat Measured using dual-energy x-ray absorptiometry Change from baseline to 6 months
Other Grip strength Evaluated with a Jamar Handheld dynamometer Change from baseline to 6 months
Other Adverse Events Number of non-serious and serious adverse events Through study completion at 6 months
Other Short Physical Performance Battery Objective assessment tool for evaluating lower extremity function Change from baseline to 6 months
Other Lipoprotein levels Measured using automated enzymatic/colorimetric assays Change from baseline to 6 months
Primary Adherence Percent of study visits attended Through study completion at 6 months
Secondary Recruitment Number of participants recruited Through study completion at 6 months
Secondary 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 Change from baseline to 6 months
Secondary 6-Minute Walk Test A performance based measure of functional exercise capacity. Change from baseline to 6 months
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