Efficacy of Immunoadsorption for Treatment of Persons With Alzheimer Dementia and Agonistic Autoantibodies Against alpha1A-adrenoceptor (IMAD)
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 2
- 主要终点
- Changes in cerebral blood flow, estimated by Arterial Spin Labeling MRI
研究概览
简要总结
Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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./
- •degree or symptomatic sick sinus syndrome without implanted pacemaker, history of myocardial infarct, bypass or other revascularization measures, valvular heart defect (≥
- •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
结局指标
主要结局
Changes in cerebral blood flow, estimated by Arterial Spin Labeling MRI
时间窗: 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
次要结局
- Laboratory parameters in liquor associated with Alzheimer's disease(Measurement at 2 times: before IA (= baseline) and 12 months after IA)
- Cognition (changes/improvement/impairment)(Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA)
- Vascular effects(Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA)
- Renal function(Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA)