immunoadsorption for treatment of alzheimer's disease

Conditions: Alzheimer Dementia

Summary: efficacy of immunoadsorption for treatment of persons with alzheimer dementia and agonistic autoantibodies against alpha1a-adrenoceptor.

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.

Eligibility criteria:
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

Keywords: adasorb apheresis globaffin adsorber agonistic autoantibodies immunoadsorption alzheimer dementia