Immunoadsorption for Treatment of Alzheimer's Disease

Not Applicable

Terminated

• Conditions: Alzheimer Dementia
• Interventions: Device: Immunoadsorption with Globaffin

• 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

Arm && Interventions

Group	Intervention	Description
Immunoadsorption with Globaffin for Alzheimer Dementia	Immunoadsorption with Globaffin	Immunoadsorption with Globaffin

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