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

NCT05068830 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: 2018/7022018-000148-24
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction Given that exercise training reduces the risk of developing Alzheimer's disease (AD), induces changes in the blood composition and has widespread systemic benefits, it is reasonable to hypothesize that exercised plasma may have rejuvenative properties. The main objective is to test safety and tolerability of transfusing exercised plasma (ExPlas) from young, healthy, fit adults to patients with early AD. The study is a pilot for a future efficacy study. The key secondary objectives are examining the effect of plasma transfusions on cognitive function, fitness level, vascular risk profile, assessment of cerebral blood flow and hippocampal volume, quality of life, functional connectivity assessed by resting state functional MRI and biomarkers in blood and cerebrospinal fluid. Methods and analysis ExPlas is a double-blinded, randomized controlled clinical single center trial. Patients aged 50-75 years with diagnosis mild cognitive impairment or early AD will be recruited from two Norwegian hospitals. ExPlas is plasma drawn by plasmapheresis once a month for 4 months, from a total of 30 donors (aged 18-40, BMI ≤27 kg/m2 and VO2max \>50 mL/kg/min). All units will be virus inactivated by the Intercept method in accordance with procedures at St. Olavs Hospital. Comparison with isotonic saline allows differentiation from a non-blood product. The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions divided over three 4-weeks periods during study year-1. Follow-up examinations after 2 and 5 years after baseline is also planned. Ethics and dissemination Written informed consent will be obtained from all participants and participation is voluntary. All participants have a next of kin who will follow them throughout the study and represent the patient's interest. The study is approved by the Regional Committee for Medical and Health Research Ethics (REK 2018/702) and the Norwegian Medicines Agency (EudraCT No. 2018-000148-24).

Conditions

Alzheimer Disease

Keywords

Exercise therapy; Blood transfusion; Plasma

Outcome Measures

Primary Outcomes (2)

• Number of patients with adverse events

  as a measure for safety and tolerability of the treatment

  1 year

• Number of subjects who comply with the research protocol

  as a measure for feasibility

  1 year

Secondary Outcomes (22)

• CERAD-test

  1, 2 and 5 years

• MMSE

  1, 2, and 5 years

• Trail-Making test A and B

  1, 2, and 5 years

• Clock Drawing Test

  1, 2, and 5 years

• Controlled Oral Word Association Test (COWAT)-FAS

  1, 2, and 5 years

Study Arms (3)

Exercised plasma (ExPlas)

EXPERIMENTAL

Dosage: 200 mL at every time point Dosage form: Solution for intravenous infusion Frequency of administration: 12 ExPlas transfusions during the time span of one year (weekly transfusions in 3 four-week periods)

Drug: ExPlas

Octaplasma

ACTIVE COMPARATOR

Dosage: 200 mL at every time point Dosage form: Solution for intravenous infusion Frequency of administration: 12 Octaplasma transfusions during the time span of one year (weekly transfusions in 3 four-week periods)

Drug: Octaplasma

Saline

PLACEBO COMPARATOR

Dosage: 200 mL at every time point Dosage form: Solution for intravenous infusion Frequency of administration: 12 saline infusions during the time span of one year (weekly transfusions in 3 four-week periods)

Drug: Saline

Interventions

ExPlas DRUG

ExPlas (plasma from fit donors) is a Investigational Medicinal Product. ExPlas is plasma drawn by plasmapheresis once a month for 4 months, from a total of 30 donors (aged 18-40, BMI ≤27 kg/m2 and VO2max \>50 mL/kg/min) at the Blood Bank at St. Olavs Hospital. All unites will be virus inactivated by the Intercept method (Cerus corporation, US) in accordance with the procedures at Blood Bank at St. Olavs Hospital. The transfusion volume will be 200 mL at every time point. The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions during the time span of one year (weekly transfusions in 3 four-week periods) and one round of examinations 2 years after baseline. A follow-up visit is also planned 5 years after baseline.

Exercised plasma (ExPlas)

Octaplasma DRUG

Octaplasma is defined as a Investigational Medicinal Product. Octaplasma is human pooled plasma produced by Octapharma (Lachen, Switzerland). The transfusion volume will be 200 mL at every time point . The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions during the time span of one year (weekly transfusions in 3 four-week periods) and one round of examinations 2 years after baseline. A follow-up visit is also planned 5 years after baseline.

Octaplasma

Saline DRUG

Saline is provided by the hospital pharmacies in Central Norway. The infusion volume will be 200 mL at every time point. The main study consists of 6 rounds of examinations in addition to 12 saline infusions during the time span of one year (weekly transfusions in 3 four-week periods) and one round of examinations 2 years after baseline. A follow-up visit is also planned 5 years after baseline.

Saline

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead
• St. Olavs Hospital: collaborator

Study Sites (1)

Department of Neurology and Clinical Neurophysiology, St Olavs Hospital

Trondheim, Norway

Location

Related Publications (1)

• Tari AR, Berg HH, Videm V, Brathen G, White LR, Rosbjorgen RN, Scheffler K, Dalen H, Holte E, Haberg AK, Selbaek G, Lydersen S, Duezel E, Bergh S, Logan-Halvorsrud KR, Sando SB, Wisloff U. Safety and efficacy of plasma transfusion from exercise-trained donors in patients with early Alzheimer's disease: protocol for the ExPlas study. BMJ Open. 2022 Sep 6;12(9):e056964. doi: 10.1136/bmjopen-2021-056964.

  PMID: 36538409 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Ulrik Wisløff, PhD, Prof

  Cardiac Exercise Research Group at the Department of Circulation and Medical Imaging, NTNU

  PRINCIPAL INVESTIGATOR

• Sigrid Botne Sando, MD, PhD

  Department of Neurology and Clinical Neurophysiology, St. Olavs University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blinded, randomized controlled clinical phase II trial

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: October 6, 2021
• Study Start: September 17, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2031
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After study completion
• Access Criteria: Collaborative research projects

Locations

NO (1)