Study to Explore the Safety and Feasibility of Allogeneic Young Plasma Infusion in Older Adults

Early Phase 1

Withdrawn

• Conditions: Heart Failure; Frailty Syndrome
• Interventions: Biological: Allogeneic Young Plasma

• Registration Number: NCT04241159
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

Evaluate the feasibility of administering plasma (PF24) acquired from donors of a young chronological age intravenously to older adults at WFBMC while also exploring its effects on age-related functional decline

Detailed Description

A Small-Scale Study to Explore the Safety and Feasibility of Allogeneic Young Plasma Infusion in Older Adults Experiencing Disability Across the Spectrum of Frailty Syndrome

Plasma (PF24) will be transfused into enrolled male and female geriatric patients aged 65-80 who have a diagnosis of frailty (Fried Frailty score of 3 or greater) or HFpEF. The experimental dosing will consist of once weekly administration of PF24 over a period of 8 consecutive weeks (8 total doses over 56 days). Primary and secondary endpoints will measure safety and feasibility of infusing PF24 in this study population. Tertiary endpoints will include measurement of the Fried Frailty score, various cognitive testing, measurement of VO2max, and blood biomarkers associated with aging. We will measure change from baseline 1 week after the 8th infusion of PF24. Test of durability will occur 5 weeks after the 8th infusion of plasma.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2019-11
• Study First Submitted: 2020-01-13
• Study First Submitted QC: 2020-01-23
• Study First Posted: 2020-01-27
• Study Start: 2020-05
• Last Update Submitted: 2020-05-21
• Last Update Posted: 2020-05-22
• Primary Completion: 2020-08
• Study Completion: 2020-08

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• English speaking elderly males and females, aged 65-80 years, referred by the Gerontology Department and the Cardiology Clinic of the Wake Forest Baptist Health Sticht Center for Aging.
• a score of 3 or greater (at least frail status) as demonstrated by the Fried Frailty criteria.

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Exclusion Criteria

• Unable or unwilling to give informed consent in either study group
• Current psychiatric disorder not currently under control or being adequately treated
• Current consumption of more than 14 alcoholic drinks per week
• Self-reported inability to walk across a small room
• Residence in a nursing home
• Previous MOCA score below 21
• Difficulty in communication with study personnel due to speech or hearing problems
• Other medical, psychiatric, or behavioral factors that in the judgment of the Principal Investigator may interfere with study participation or the ability to follow the intervention protocol
• Elective surgery, planned prior to signing consent
• Severe osteoarthritis
• Rheumatoid arthritis
• Severe B/L hip, knee, or hand pain (>7/10 on pain scale)
• Cancer requiring treatment in the past three years, except for non-melanoma skin cancers or cancers that have clearly been cured or in the opinion of the investigator carry an excellent prognosis (e.g., Stage 1 cervical cancer)
• Pulmonary disease including VQ mismatch/diffusion limitation, diminished inspired O2, hypoventilation, pulmonary fibrosis, or sarcoidosis
• Current tobacco use (smoke/chew)
• Currently prescribed corticosteroids
• Patients taking nucleoside analogues (Zebularine, 5-azaC, Decitabine)
• Patients on non-nucleoside analogues (Procaine, procainamide, hydralazine)
• History of an inherited bleeding disorder or vitamin K deficiency
• Cardiovascular disease (excluding HFpEF), clinically significant aortic stenosis, history of cardiac arrest, use of a cardiac defibrillator or uncontrolled angina.
• Parkinson's disease or other serious neurological disorder
• MMS score < 18
• Renal disease (any stage, inappropriate for age; Cr Cl < 60)
• Hypoalbuminemia, with serum albumin level < 3.5 g/dL
• History of IgA deficiency
• History of hypersensitivity to frozen plasma (PF24) or to plasma-derived products including any plasma protein
• Active hepatitis or history of liver transplant
• Anemia or polycythemia: Male - Hgb level below 12 or above 17.5 g/dL and/or HCT of 41%-53%. Female: Hgb level below 10.0 or above 16.0 g/dL and/or HCT 36%-46%
• Current use of anti-coagulants
• History of DMI or DMII
• Peripheral vascular disease
• Brain aneurysm or intracranial hemorrhage within the past 6 months
• History of Hepatitis B, Hepatitis C, or HIV infection
• Other illness of such severity that life expectancy is considered to be less than 12 months
• Patients with initial VO2max that falls below expected value or that does not meet a minimum VO2max of 20 mL * kg * min (in order to demonstrate a more clinically meaningful increase)
• Uncontrolled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg)
• CVA, hip fracture, B/L hip or knee replacement, or spinal surgery in the past 6 months
• Serious conduction disorder (e.g., 3rd degree heart block), uncontrolled arrhythmia, or new Q waves or ST-segment depressions (>3 mm) on ECG
• Myocardial infarction, major heart surgery (i.e., valve replacement or bypass surgery), stroke, deep vein thrombosis or pulmonary embolism in the past 6 months
• Undergoing physical therapy or cardiopulmonary rehabilitation
• Currently enrolled in another randomized trial involving lifestyle or pharmaceutical interventions
• Currently on an anaerobic/aerobic exercise plan
• Inability or unwillingness to return for all transfusions/FU visits

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Geriatric participants with frailty	Allogeneic Young Plasma	Geriatric participants aged 65-80 who have a diagnosis of frailty (Fried Frailty score of 3 or greater). Experimental dosing will consist of once weekly administration of PF24 over a period of 8 consecutive weeks (8 total doses over 56 days).
Geriatric participants with HFpEF	Allogeneic Young Plasma	Geriatric participants aged 65-80 who have a diagnosis of HFpEF. Experimental dosing will consist of once weekly administration of PF24 over a period of 8 consecutive weeks (8 total doses over 56 days).

Primary Outcome Measures

Name	Time	Method
Frequency of adverse events	Post 5 weeks after the last infusion of plasma	The primary outcomes of this phase 0 study are built upon evaluating the outcome of safety with administering plasma (PF24) acquired from donors of a young chronological age intravenously to older adults at WFBMC, as evidenced by lack of any grade 4-5 adverse events and \>/=50% grade 3-4 adverse events, as defined by NCI CTCAE v5.0. Grade 1-2 events will be recorded for statistical purposes.

Secondary Outcome Measures

Name	Time	Method
Study participant retention	Post 5 weeks after the last infusion of plasma	Secondary outcomes include indicators of feasibility as assessed by measuring study participant retention \>/= 80%
Study participants ability to complete the Fried Frailty Assessment	Study endpoint weeks 11 and 15	Measurement of the Fried Frailty Score - The stages of frailty based on the Fried Frailty assessment criteria: a score of 0 means that a person is robust or not frail. Persons with a score of 1 or 2 are at intermediate risk for adverse outcomes or are considered to be pre-frail. A score of 3-5 indicates that someone is frail

Trial Locations

Locations (1)

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States