Alzheimer Dementia
Conditions
Keywords
ADAsorb apheresis, Globaffin adsorber, Agonistic Autoantibodies, Immunoadsorption, Alzheimer Dementia
Brief summary
Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor.
Detailed description
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.
Interventions
DEVICEImmunoadsorption with Globaffin
Immunoadsorption for treatment of persons with Alzheimer Dementia
Sponsors
University Medicine Greifswald
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in cerebral blood flow, estimated by Arterial Spin Labeling MRI | Measurement at 4 times over a 12 months period: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | Measurement of cerebral blood flow and evaluation of changes between baseline and condition after intervention over a 12 months period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognition (changes/improvement/impairment) | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | Measurement by Alzheimer's Disease Assessment Scale (ADAS-cog) |
| Vascular effects | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | Left ventricular ejection fraction (LVEF) |
| Renal function | Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA | Nephrosonography: position, size and surface of kidneys, echogenicity, presence and assessment of cysts and tumors, calcifications, nephroliths |
| Laboratory parameters in liquor associated with Alzheimer's disease | Measurement at 2 times: before IA (= baseline) and 12 months after IA | Measurement of beta-amyloid and tau species concentrations in liquor (optional; only if subjects gave informed consent in lumbar puncture) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum analytics | 12 months | analysis of agonistic autoantibodies against alpha1A adrenoceptor and measurement of different biomarkers, metabolites associated with Alzheimer's disease in blood samples |
Countries
Germany
Outcome results
None listed