Clinical trial NCT03132272: Immunoadsorption for Treatment of Alzheimer's Disease
Official title: Efficacy of Immunoadsorption for Treatment of Persons With Alzheimer Dementia and Agonistic Autoantibodies Against alpha1A-adrenoceptor (IMAD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Alzheimer Dementia
Keywords: ADAsorb apheresis
Globaffin adsorber
Agonistic Autoantibodies
Immunoadsorption
Alzheimer Dementia
Lead sponsor: University Medicine Greifswald
Sponsor class: OTHER
First posted: 2017-04-27
Enrollment: 11
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Changes in cerebral blood flow, estimated by Arterial Spin Labeling MRI
timeFrame: 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 outcomes:
measure: Cognition (changes/improvement/impairment)
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Cognition (changes/improvement/impairment)
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Cognition (changes/improvement/impairment)
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Cognition (changes/improvement/impairment)
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Vascular effects
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Vascular effects
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Vascular effects
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Vascular effects
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Vascular effects
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Renal function
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Renal function
timeFrame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
measure: Laboratory parameters in liquor associated with Alzheimer's disease
timeFrame: Measurement at 2 times: before IA (= baseline) and 12 months after IA
Other outcomes:
measure: Serum analytics
timeFrame: 12 months
Locations:
city: Greifswald
country: Germany
facility: University Medicine Greifswald
state: Mecklenburg-Vorpommern
Study officials:
affiliation: University Medicine Greifswald
name: Marcus Dörr, Prof.Dr.med.
role: PRINCIPAL_INVESTIGATOR
References: