Plasmapheresis Versus Plasma Infusion from Young APOE3 Homozygotes Into MCI APOE4 Homozygotes to Slow Disease Progression

Plasmapheresis Versus Plasma Infusion from Young APOE3 Homozygotes Into MCI APOE4 Homozygotes to Slow Disease Progression: an Unblinded Phase 1 Safety, Methodological and Exploratory Biomarkers Study.

Determine safety of plasma infusion or exchange in APOE 44 patients.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Biological: Plasmapheresis; Biological: Plasma infusion

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Patient age 50 to 75.
• APOE 44 homozygote.
• Meets the Petersen criteria for MCI (41).
• Clinical Dementia Rating (CDR) of 0.5 and Mini Mental Status Examination (MMSE) of 24 to 30 inclusive.
• Has an informant who the investigator judges has sufficient patient contact to provide accurate information.
• Stable depression and or anxiety.
• Stable psychoactive medication for 6 weeks.

Exclusion criteria

• History of severe reaction to plasma or plasma derived products which include but not limited to severe allergic reaction, anaphylactic reaction and transfusion related acute lung injury (TRALI).
• Patients who do not want to receive blood transfusion for religious or cultural reasons such as Jehovah Witness Faith.
• Has a medical condition that would interfere with participation such as congestive heart failure (New York Heart Association Class III or IV), unstable angina, moderate to severe renal impairment, liver failure, and poorly controlled diabetes.
• History of autoimmune disease considered clinically significant or requiring chronic steroid or immune suppression medication.
• History of being HIV +.
• History of +VE test result indicating active hepatitis C or B (defined as both hepatitis B surface antigen and hepatitis core antibody +VE).
• Uncontrolled hypertension as defined by systolic/diastolic BP three times more than 165/100.
• No venous access for plasma exchange therapy.
• Any neurological condition that could be contributing to cognitive decline such as Lewy body disease, front temporal dementia, strokes or other cerebrovascular disease, head trauma, substance abuse, multiple sclerosis, Vitamin B12 deficiency, thyroid deficiency.
• Epileptic seizures within 10 years of screening.
• Cancer diagnosis (other than non-melanoma skin cancer) in the last 5 years.
• More than 1 subcortical stroke or more than 1 cortical stroke.
• Unable to have an MRI.
• MRI showing acute or subacute hemorrhage, evidence of normal pressure hydrocephalus, hemispheric infarcts, glioma or other brain tumor that could contribute to cognitive decline.
• Unstable psychiatric condition.
• On another experimental treatment study or has been on one in the last 3 months.
• If a patient consents to lumbar puncture (LP), they will be excluded from LP if any contraindication to having an LP is present. Examples are platelet count<100,000, spine deformity or contraindication to come off blood thinner for the LP. Patients may still participate in the rest of the study without having and LP.
• Any unspecified reason that the investigator finds the patient unsuitable to take part.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plasmapheresis; 3 patients will have monthly plasmapheresis for 6 months and followed for a total of 12 months	Biological: Plasmapheresis; Patient will have monthly plasma exchange with young ApoE 33 plasma. Each exchange will be 1.5 volume of patient's plasma
Experimental: Plasma infusion; 3 patients will have biweekly plasma infusion for 6 months and followed for 12 months	Biological: Plasma infusion; Infuse every two weeks with ApoE33 young plasma (1unit) for 6 months
No Intervention: Control group; 3 patients will be followed for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of adverse events reported	One year

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Neill R Graff-Radford, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): February 16, 2024
• Study Completion (Actual): February 16, 2024

Study Registration Dates

• First Submitted: March 21, 2019
• First Submitted That Met QC Criteria: March 21, 2019
• First Posted (Actual): March 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 30, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease Attributes; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Disease Progression
• Other Study ID Numbers: 18-007034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No