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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-000148-24 | EudraCT Number |
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| Name | Class |
|---|---|
| St. Olavs Hospital | OTHER |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
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| 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) |
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| 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) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| CERAD-test | 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. |
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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):
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:
Related to medical history:
Related to medications or other treatments:
Related to magnetic resonance imaging:
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.
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Neurology and Clinical Neurophysiology, St Olavs Hospital | Trondheim | Norway |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36538409 | Derived | 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. |
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To be decided
After study completion
Collaborative research projects
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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Double blinded, randomized controlled clinical phase II trial
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| 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. |
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| 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. |
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| 1, 2 and 5 years |
| MMSE | 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. | 1, 2, and 5 years |
| Trail-Making test A and B | 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. | 1, 2, and 5 years |
| Clock Drawing Test | 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. | 1, 2, and 5 years |
| Controlled Oral Word Association Test (COWAT)-FAS | 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. | 1, 2, and 5 years |
| Visual Object and Space Perception (VOSP) Silhouettes | 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. | 1, 2, and 5 years |
| Clinical Dementia Rating Scale Global score and Sum of Boxes | 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. | 1, 2, and 5 years |
| The Lawton Instrumental Activities of Daily Living Scale (IADL) | 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. | 1, 2, and 5 years |
| 6 minutes' walk test | Change in 6 minutes' walk-test | 1, 2, and 5 years |
| Functional MRI | 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. | 1, 2, and 5 years |
| SF-36 | Quality of Life SF-36 Questionnaire. Computer-based scoring services for the SF-36v2 are available through QualityMetric™ or its licensed certified vendors. | 1, 2, and 5 years |
| Biomarker profile in blood | 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. | 1, 2, and 5 years |
| Biomarker profile in cerebrospinal fluid | 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. | 1, 2, and 5 years |
| Echocardiography - Cardiac dimensions - Left ventricular end diastolic diameter | Changes in cardiac dimensions - left ventricular end diastolic diameter (mm). | 1, 2, and 5 years |
| Echocardiography - Cardiac dimensions - Right ventricular dimension | Changes in cardiac dimensions - right ventricular dimension (mm). | 1, 2, and 5 years |
| Echocardiography - Cardiac volumes - Left ventricular and diastolic volume. | Changes in cardiac volumes - left ventricular and diastolic volume (mL). | 1, 2, and 5 years |
| Echocardiography - Cardiac volumes - Right ventricular volume | Changes in cardiac volumes. Right ventricular volume (mL). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Ejection fraction | Changes in functional indices - ejection fraction (%). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Left ventricular strain | Changes in functional indices - left ventricular strain (%). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Ventricular velocity | Changes in functional indices - ventricular velocity (cm/s). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Right ventricular strain | Changes in functional indices - right ventricular strain (%). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Left ventricular stiffness | Changes in functional indices - left ventricular stiffness. | 1, 2, and 5 years |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D017670 |
| Sodium Compounds |