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

NCT ID: NCT05068830

Last Updated: 2024-11-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-17
• Study Completion Date: 2026-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Exercised plasma (ExPlas)

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)

Group Type: EXPERIMENTAL

ExPlas

Intervention Type: 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.

Octaplasma

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)

Group Type: ACTIVE_COMPARATOR

Octaplasma

Intervention Type: 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.

Saline

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)

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: 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.

Interventions

ExPlas

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.

Intervention Type: DRUG

Octaplasma

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.

Intervention Type: DRUG

Saline

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.

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

Norwegian University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ulrik Wisløff, PhD, Prof

Role: PRINCIPAL_INVESTIGATOR

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

Sigrid Botne Sando, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Department of Neurology and Clinical Neurophysiology, St Olavs Hospital

Trondheim, , Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Atefe R. Tari

Role: CONTACT

atefe.r.tari@ntnu.no

+47 48079041

Facility Contacts

Sigrid Botne Sando, MD, PhD

Role: primary

sigrid.b.sando@ntnu.no

References

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.

Reference Type: DERIVED

PMID: 36538409 (View on PubMed)

Other Identifiers

2018-000148-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2018/702

Identifier Type: -

Identifier Source: org_study_id