Clinical trial NCT05284604: Mesenchymal Stem Cells for Age-Related Frailty
Official title: A Pilot Study of Mesenchymal Stem Cells as Novel Therapy for Age-Related Frailty in Veterans
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Frailty
Keywords: Frailty
Aging
Mesenchymal Stem Cells
Physical Function
Cognitive Function
Sarcopenia
Osteoporosis
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Michael E. DeBakey VA Medical Center
name: Baylor College of Medicine
First posted: 2022-03-17
Enrollment: 0
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are assigned to one of three groups in parallel for the duration of the study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Adherence
timeFrame: Through study completion at 6 months
Secondary outcomes:
measure: Recruitment
timeFrame: Through study completion at 6 months
measure: Modified Physical Performance Test
timeFrame: Change from baseline to 6 months
measure: 6-Minute Walk Test
timeFrame: Change from baseline to 6 months
Other outcomes:
measure: 4-minute walk gait speed
timeFrame: Change from baseline to 6 months
measure: Activities of daily living (ADL) and instrumental ADL
timeFrame: Change from baseline to 6 months
measure: High-Sensitivity C-reactive protein
timeFrame: Change from baseline to 6 months
measure: Knee extensor strength
timeFrame: Change from baseline to 6 months
measure: Soluble tumor necrosis factor receptor 1 (sTNF)
timeFrame: Change from baseline to 6 months
measure: Interleukin-6
timeFrame: Change from baseline to 6 months
measure: Bone mineral density of the lumbar spine and hip
timeFrame: Change from baseline to 6 months
measure: Lean body mass
timeFrame: Change from baseline to 6 months
measure: Visceral fat mass
timeFrame: Change from baseline to 6 months
measure: Bone microarchitecture
timeFrame: Change from baseline to 6 months
measure: Bone strength
timeFrame: Change from baseline to 6 months
measure: Trabecular bone score
timeFrame: Change from baseline to 6 months
measure: Cognition
timeFrame: Change from baseline to 6 months
measure: Quality of Life
timeFrame: Change from baseline to 6 months
measure: Body fat
timeFrame: Change from baseline to 6 months
measure: Grip strength
timeFrame: Change from baseline to 6 months
measure: Adverse Events
timeFrame: Through study completion at 6 months
measure: Short Physical Performance Battery
timeFrame: Change from baseline to 6 months
measure: Lipoprotein levels
timeFrame: Change from baseline to 6 months
Locations:
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center, Houston, TX
state: Texas
Study officials:
affiliation: Michael E. DeBakey VA Medical Center, Houston, TX
name: Dennis T Villareal, MD
role: PRINCIPAL_INVESTIGATOR
References: