Immunoadsorption for Treatment of Alzheimer's Disease

Study Overview
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Brief Summary
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Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor.

Detailed Description
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The IMAD trial outlined aims to ascertain whether the positive effects of immunoadsorption (IA) on slowing down dementia progression, shown in a pilot trial, can be replicated in a slightly larger number of subjects and to comprehensively investigate the effects by a combination of brain and vessel imaging along with cognitive tests and further state-of-the-art cardiovascular, cerebrovascular and laboratory examinations. If the trial results underpin the hypothesis that IA effectively counteracts pathophysiological impairments and dementia-related cognitive decline, it may open up a new treatment approach against dementia, namely the reversal or avoidance of further vascular damage by the removal of agonistic autoantibodies (agAAB) in agAAB-positive persons. The aim of this study is (beside of safety) to demonstrate the stop of the vascular remodeling and cognition decline by immunoadsorption, a therapeutic method which is well established in cardiology and nephrology.

Official Title
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Efficacy of Immunoadsorption for Treatment of Persons With Alzheimer Dementia and Agonistic Autoantibodies Against alpha1A-adrenoceptor (IMAD)

Conditions
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Alzheimer Dementia

Intervention / Treatment
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* Device: Immunoadsorption with Globaffin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 55-85 years of age Diagnosis of Alzheimer's disease Presence of agAAB against alpha1-adrenoceptor Mini mental state examination (MMSE) score between 19 and 26 Written informed consent given Exclusion Criteria: Haemanalysis: Presence of autoantibodies against the N-methyl-D-aspartate (NMDA) receptor Defective blood coagulation at time of inclusion Severe protein deficiency disorders manifest Vitamin/Folic acid deficiency (substitution allowed) Active infectious disease, or signs of ongoing infection with C-reactive protein (CRP) >10mmol/L Impaired renal function (serum creatinine >220 μmol/L) Any disease requiring immunosuppressive drugs or therapeutic antibodies Non curative treated malignant disease or another life-threatening disease with poor prognosis (survival less than 2 years), except for basal-cell carcinoma Unstable angina pectoris, atrioventricular block (AV block) 2./3. degree or symptomatic sick sinus syndrome without implanted pacemaker, history of myocardial infarct, bypass or other revascularization measures, valvular heart defect (≥ 2. Degree) Severely reduced left ventricular systolic function (LVEF < 30%) and/or heart failure symptoms according to New York Heart Association (NYHA) class III/IV Clinical manifestation of arterial disease, vascular surgery: No Arteria Carotis Interna (ACI) Stenosis > 60%, peripheral artery occlusive disease (PAOD) > IIb, NASCET, no clinical manifest apparent stroke in anamnesis, MRI: no diffusion disorder, no expired territorial stroke Endocrine disorder excluding diabetes mellitus Severe hepatic damages (CHILD-Score < 4) Severe mental disorders (bipolar disorder, schizophrenia, depression) requiring treatment Alcohol or drug abuse Drug therapy against dementia since less than 3 months Psychopharmacological drug therapy since less than 3 months Dialysis requirement MRI contraindications (e.g. heart pacemaker) Legal tutelage Previous treatments with IA or immunoglobulin Inability to undergo the study procedure (IA on five consecutive days with subsequent Immunoglobulin G (IgG) substitution) treatment with angiotensin-converting-enzyme inhibitors (ACE inhibitors) during the IA (angiotensin receptor blockers (AT-blockers) possible) Participation in any other clinical/interventional study within less than 30 days prior to screening date

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunoadsorption with Globaffin for Alzheimer Dementia<br>Immunoadsorption with Globaffin | Device: Immunoadsorption with Globaffin<br>* Immunoadsorption for treatment of persons with Alzheimer Dementia<br>* Other names: ADAsorb apheresis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cerebral blood flow, estimated by Arterial Spin Labeling MRI | Measurement of cerebral blood flow and evaluation of changes between baseline and condition after intervention over a 12 months period | Measurement at 4 times over a 12 months period: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognition (changes/improvement/impairment) | Measurement by Alzheimer's Disease Assessment Scale (ADAS-cog) | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Cognition (changes/improvement/impairment) | Measurement by Mini Mental Status Examination-2 (MMSE) | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Cognition (changes/improvement/impairment) | Measurement by California Verbal Learning Test (CVLT) | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Cognition (changes/improvement/impairment) | Measurement by Benton Test | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Vascular effects | Left ventricular ejection fraction (LVEF) | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Vascular effects | Endothelial function: measurement by Endo-PAT | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Vascular effects | Arterial stiffness: measurement by Endo-PAT | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Vascular effects | Arterial stiffness: measurement by Mobil-O-Graph (pulse wave analysis) | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Vascular effects | Oxygen saturation: transcutaneous oxygen pressure examinations by PRÉCISE 8008, Medicap | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Renal function | Nephrosonography: position, size and surface of kidneys, echogenicity, presence and assessment of cysts and tumors, calcifications, nephroliths | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Renal function | Estimated glomerular Filtration rate (eGFR) using Modification of Diet in Renal Disease (MDRD) formula | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | 
| Laboratory parameters in liquor associated with Alzheimer's disease | Measurement of beta-amyloid and tau species concentrations in liquor (optional; only if subjects gave informed consent in lumbar puncture) | Measurement at 2 times: before IA (= baseline) and 12 months after IA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADAsorb apheresis, Globaffin adsorber, Agonistic Autoantibodies, Immunoadsorption, Alzheimer Dementia