Immunoadsorption for Treatment of Alzheimer's Disease

Not Applicable

Terminated

• Conditions: Alzheimer Dementia

• Registration Number: NCT03132272
• Lead Sponsor: University Medicine Greifswald

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.

Study Timeline

• Study Start: 2016-09-15
• Study First Submitted: 2016-11-16
• Study First Submitted QC: 2017-04-26
• Study First Posted: 2017-04-27
• Primary Completion: 2020-10-12
• Study Completion: 2020-10-12
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-04
• Last Update Posted: 2021-03-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Vascular effects	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA	Oxygen saturation: transcutaneous oxygen pressure examinations by PRÉCISE 8008, Medicap
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)
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 Benton Test
Renal function	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA	Estimated glomerular Filtration rate (eGFR) using Modification of Diet in Renal Disease (MDRD) formula

Trial Locations

Locations (1)

University Medicine Greifswald; 🇩🇪 Greifswald, Mecklenburg-Vorpommern, Germany