Safety and Efficacy of Plasma Transfusion From Exercise-trained Donors in Patients With Early Alzheimer's Disease
- Conditions
- Alzheimer Disease
- Interventions
- Drug: ExPlasDrug: OctaplasmaDrug: Saline
- Registration Number
- NCT05068830
- Lead Sponsor
- Norwegian University of Science and Technology
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Exercised plasma (ExPlas) 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) Octaplasma 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) Saline 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)
- Primary Outcome Measures
Name Time Method Number of patients with adverse events 1 year as a measure for safety and tolerability of the treatment
Number of subjects who comply with the research protocol 1 year as a measure for feasibility
- Secondary Outcome Measures
Name Time Method The Lawton Instrumental Activities of Daily Living Scale (IADL) 1, 2, and 5 years Change in The Lawton Instrumental Activities of Daily Living Scale (IADL). The Lawton Instrumental Activities of Daily Living Scale (IADL) evaluates the person's ability to perform complex everyday activities. The score ranges from 8-31. Higher scores indicate lower functional level.
6 minutes' walk test 1, 2, and 5 years Change in 6 minutes' walk-test
Trail-Making test A and B 1, 2, and 5 years Change in performance in Trail-Making test A and B. The Trail Making Tests are scored by how long it takes to complete the tests. Norms for completion time variate with age and educational level. Longer completion time indicates impaired visual attention, processing speed and executive function.
Controlled Oral Word Association Test (COWAT)-FAS 1, 2, and 5 years Change in scores in Controlled Oral Word Association Test (COWAT)-FAS. Scoring is based on how many words the person produces within 1 minute. The minimum score is 0, and there is no maximum score. Higher scores indicate better verbal fluency. Scoring norms are based on the persons age and education level.
CERAD-test 1, 2 and 5 years Change in performance in the CERAD (The Consortium to Establish a Registry for Alzheimer's Disease) Ten word Test. CERAD Word List consists of three test parts; immediate recall, delayed recall and recognition. The scoring range for immediate recall is 0-30, for delayed recall 0-10 and for recognition 0-20. Higher scores indicate better learning performance, memory performance and recognition performance.
Clock Drawing Test 1, 2, and 5 years Change in scores in the Clock Drawing Test. The Clock Drawing Test has a scoring range 0-5. Higher scores indicate normal cognitive function. Lower scores \<4 may indicate cognitive impairment, spatial dysfunction or neglect.
Functional MRI 1, 2, and 5 years Change in/Reduced hippocampal atrophy and preservation of functional connectivity assessed by resting state functional MRI. A secondary aim is to identify any effect of treatment group on MRI markers of both neurodegenerative and cerebrovascular disease.
Echocardiography - Cardiac volumes - Left ventricular and diastolic volume. 1, 2, and 5 years Changes in cardiac volumes - left ventricular and diastolic volume (mL).
Echocardiography - Functional indices - Ventricular velocity 1, 2, and 5 years Changes in functional indices - ventricular velocity (cm/s).
Echocardiography - Cardiac dimensions - Left ventricular end diastolic diameter 1, 2, and 5 years Changes in cardiac dimensions - left ventricular end diastolic diameter (mm).
Clinical Dementia Rating Scale Global score and Sum of Boxes 1, 2, and 5 years Change in Clinical Dementia Rating Scale Global score and Sum of Boxes. Clinical Dementia Rating Scale (CDR) is a clinical scale for the staging of dementia. The Global Score ranges dementia severity from 0-3. The Sum of Boxes ranges dementia severity from 0-18. Higher scores indicate more severe disease.
Echocardiography - Functional indices - Right ventricular strain 1, 2, and 5 years Changes in functional indices - right ventricular strain (%).
MMSE 1, 2, and 5 years Change in the Mini-Mental State Examination Score. An MMSE score of ≥20 is criteria for inclusion. Higher scores \>28 indicate normal cognitive function. Scores in the middle range 25-27 may indicate cognitive impairment. Lower scores \<24 indicate cognitive impairment.
Visual Object and Space Perception (VOSP) Silhouettes 1, 2, and 5 years Change in scores in Visual Object and Space Perception (VOSP) Silhouettes. Visual Object and Space Perception (VOSP) Silhouettes has a scoring range 0-30. Higher scores \> 20 indicate normal visuospatial function, and lower scores \< 20 indicate visuospatial dysfunction.
SF-36 1, 2, and 5 years Quality of Life SF-36 Questionnaire. Computer-based scoring services for the SF-36v2 are available through QualityMetric™ or its licensed certified vendors.
Biomarker profile in blood 1, 2, and 5 years Change in biomarkers in blood (APOE). As there exist no single ideal biomarker of AD this endpoint is partly exploratory. Biological material will be stored for future analysis in the search for new biomarkers.
Biomarker profile in cerebrospinal fluid 1, 2, and 5 years Change in biomarkers in cerebrospinal fluid (Amyloid Beta 1-42, Amyloid Beta 1-40, phosphor tau and total tau). As there exist no single ideal biomarker of AD this endpoint is partly exploratory. Biological material will be stored for future analysis in the search for new biomarkers.
Echocardiography - Cardiac dimensions - Right ventricular dimension 1, 2, and 5 years Changes in cardiac dimensions - right ventricular dimension (mm).
Echocardiography - Functional indices - Left ventricular strain 1, 2, and 5 years Changes in functional indices - left ventricular strain (%).
Echocardiography - Functional indices - Left ventricular stiffness 1, 2, and 5 years Changes in functional indices - left ventricular stiffness.
Echocardiography - Cardiac volumes - Right ventricular volume 1, 2, and 5 years Changes in cardiac volumes. Right ventricular volume (mL).
Echocardiography - Functional indices - Ejection fraction 1, 2, and 5 years Changes in functional indices - ejection fraction (%).
Trial Locations
- Locations (1)
Department of Neurology and Clinical Neurophysiology, St Olavs Hospital
🇳🇴Trondheim, Norway