Transfusion of plasma from exercise-trained donors for early Alzheimer's patients

Safety and Efficacy of Plasma Transfusion From Exercise-trained Donors in Patients With Early Alzheimer's Disease: The ExPlas Study

This study is testing if transfusing plasma from healthy, active young people can help improve brain function and quality of life for older adults with early Alzheimer's disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 50 Years to 75 Years
• Sex: All
• Sponsor: Norwegian University of Science and Technology (Academic / other)
• Locations: 1 site (Trondheim)
• Trial ID: NCT05068830 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and tolerability of transfusing plasma from young, healthy, exercise-trained donors into patients with early Alzheimer's disease. The study is designed as a double-blinded, randomized controlled trial and will assess various outcomes, including cognitive function, vascular risk profiles, and quality of life. Participants aged 50-75 with mild cognitive impairment or early Alzheimer's will be recruited, and the study will also explore the effects of the transfusions on cerebral blood flow and hippocampal volume. This pilot study serves as a precursor to a larger efficacy trial.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 50-75 diagnosed with early Alzheimer's disease or mild cognitive impairment.

Not a fit: Patients with advanced Alzheimer's disease or those unable to communicate in Norwegian or another Scandinavian language may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel therapeutic option that enhances cognitive function and overall quality of life for patients with early Alzheimer's disease.

How similar studies have performed: While the concept of using exercise-trained plasma is novel, similar studies exploring plasma transfusions have shown promising results in other contexts.

Eligibility criteria

Patient inclusion criteria:

* Diagnosis AD in early phase according to the IWG-2 criteria.
* Mini-Mental State Examination (MMSE) Score ≥20.
* In-vivo evidence of Alzheimer´s pathology (one of the following):

  * Decreased Aβ42 together with increased t-tau or p-tau in CSF.
  * Increased tracer retention on amyloid PET.
* Availability of a next of kin who knows the patient well and is willing to accompany the subject to all trial visits and give information about the patients functional level.
* Signed informed consent.
* The patient is judged fitted for the study and capable to cooperate in treatment and follow-up.
* Ability to communicate in Norwegian or another Scandinavian language.

Patient exclusion criteria:

* Pregnancy or unwilling to use adequate birth control for the duration of and 6 months beyond study participation. Defined according to Clinical Trial Facilitation Group document "Recommendations related to contraception and pregnancy testing in clinical trials".
* Positive for Hepatitis B, Hepatitis C or HIV at screening.
* Not qualified to give consent at inclusion.
* Any other condition judged to interfere with the safety of the patient or the intent and conduct of the study.

Related to medical history:

* Stroke
* Anaphylaxis
* Prior adverse reaction to any human blood product
* Any history of a blood coagulation disorder or hypercoagulability
* Congestive heart failure, defined as any previous heart failure hospitalization, or current symptomatic heart failure in New York heart Association class ≥II with reduced, mid-range or preserved ejection fraction.
* Coagulation defect or hypercoagulopathy
* Uncontrolled hypertension
* Renal failure
* Prior intolerance to intravenous fluids
* Recent history of uncontrolled atrial fibrillation
* Bone marrow transplant
* IgA deficiency
* Severe protein S deficiency
* Thrombocytopenia (platelets \< 40 x 10 to the power of 9/L)
* Contraindication for Octaplasma

Related to medications or other treatments:

* Any concurrent use of anticoagulant therapy, clopidogrel or acetylsalicylic acid/Dipyridamol in combination.
* Initiation or change in the dosage of a acetylcholine esterase inhibitor (AChEI) or memantine during the trial (week 0-52). Participants will be urged to start on AChEI when diagnosis is communicated, and must be on a stable dose for at least one month prior to screening.
* Concurrent participation in another treatment trial for AD. If there was prior participation, the last dose of the investigational agent must have been given at least 6 months prior to screening, except if the patient received placebo medication.
* Treatment with any human blood product, including intravenous immunoglobulin, during the 6 months prior to screening or during the trial.
* Concurrent daily treatment with benzodiazepines, typical or atypical antipsychotics, long-acting opioids, or other medications that is judged to interfere with cognition. Intermittent treatment with short-acting benzodiazepines or atypical antipsychotics may be permitted, provided that no dose is administered within 72 hours prior to cognitive assessment.

Related to magnetic resonance imaging:

* Claustrophobia
* Any metallic surgical implant, like a pacemaker or clip that is incompatible with MRI.

Certain metallic implants like joint replacements may be permitted, provided that specific manufacturer specifications are available, and that the device is known to be safe for 7T MRI. In case a patient is not eligible for the 7T scanner, the 3T scanner will be used.

Where this trial is running

Trondheim

• Department of Neurology and Clinical Neurophysiology, St Olavs Hospital — Trondheim, Norway (Recruiting)

Study contacts

• Principal investigator: Ulrik Wisløff, PhD, Prof — Cardiac Exercise Research Group at the Department of Circulation and Medical Imaging, NTNU
• Study coordinator: Atefe R. Tari

Conditions Alzheimer Disease; Exercise therapy; Blood transfusion; Plasma