Mesenchymal Stem Cells for Age-Related Frailty

NCT05284604 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: E4096-P
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Frailty

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Adherence

  Percent of study visits attended

  Through study completion at 6 months

Secondary Outcomes (3)

• Recruitment

  Through study completion at 6 months

• Modified Physical Performance Test

  Change from baseline to 6 months

• 6-Minute Walk Test

  Change from baseline to 6 months

Other Outcomes (19)

• 4-minute walk gait speed

  Change from baseline to 6 months

• Activities of daily living (ADL) and instrumental ADL

  Change from baseline to 6 months

• High-Sensitivity C-reactive protein

  Change from baseline to 6 months

Study Arms (3)

Group 1

EXPERIMENTAL

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

Drug: Mesenchymal Stem Cells (MSCs)

Group 2

EXPERIMENTAL

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

Drug: Mesenchymal Stem Cells (MSCs)

Group 3

PLACEBO COMPARATOR

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

Drug: Mesenchymal Stem Cells (MSCs)

Interventions

Mesenchymal Stem Cells (MSCs) DRUG

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.

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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
• minute walk distance of \>200m and \<400m
• Willing to provide informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Michael E. DeBakey VA Medical Center: collaborator
• Baylor College of Medicine: collaborator

Study Sites (1)

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030-4211, United States

Location

MeSH Terms

Conditions

Frailty; Sarcopenia; Osteoporosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Dennis T Villareal, MD

  Michael E. DeBakey VA Medical Center, Houston, TX

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All investigators, study assessors, and participants will not be aware of the group assessments (double-blinded randomized controlled trial)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: March 17, 2022
• Study Start: January 31, 2023
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)