Clinical trial NCT04241159: Study to Explore the Safety and Feasibility of Allogeneic Young Plasma Infusion in Older Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Frailty Syndrome
Heart Failure
Keywords: Frailty
Aging
Heart failure
Plasma
Infusion
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2020-01-27
Enrollment: 0
Sex: ALL
Minimum age (years): 65
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All eligible study participants will undergo once weekly PF24 infusion for 8 weeks in the WFBH Clinical Research Unit (CRU), and return for cognitive, physical, and biomarker testing 1 week and 5 weeks after receiving the last dose of PF24.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

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

Primary outcomes:
measure: Frequency of adverse events
timeFrame: Post 5 weeks after the last infusion of plasma
Secondary outcomes:
measure: Study participant retention
timeFrame: Post 5 weeks after the last infusion of plasma
measure: Study participants ability to complete the Fried Frailty Assessment
timeFrame: Study endpoint weeks 11 and 15
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Shawn Johnson, D.O.., M.S.
role: PRINCIPAL_INVESTIGATOR
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