Immunoadsorption for Treatment of Alzheimer's Disease (IMAD)

Efficacy of Immunoadsorption for Treatment of Persons With Alzheimer Dementia and Agonistic Autoantibodies Against alpha1A-adrenoceptor (IMAD)

Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor.

Study Overview

• Status: Terminated
• Conditions: Alzheimer Dementia
• Intervention / Treatment: Device: Immunoadsorption with Globaffin

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
      • University Medicine Greifswald

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immunoadsorption with Globaffin for Alzheimer Dementia; Immunoadsorption with Globaffin	Device: Immunoadsorption with Globaffin; Immunoadsorption for treatment of persons with Alzheimer Dementia; Other Names: agonistic autoantibodies; alpha1A-adrenoceptor; Globaffin adsorber columns; ADAsorb apheresis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cerebral blood flow, estimated by Arterial Spin Labeling MRI	Measurement of cerebral blood flow and evaluation of changes between baseline and condition after intervention over a 12 months period	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognition (changes/improvement/impairment)	Measurement by Alzheimer's Disease Assessment Scale (ADAS-cog)	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Cognition (changes/improvement/impairment)	Measurement by Mini Mental Status Examination-2 (MMSE)	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Cognition (changes/improvement/impairment)	Measurement by California Verbal Learning Test (CVLT)	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Cognition (changes/improvement/impairment)	Measurement by Benton Test	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Vascular effects	Left ventricular ejection fraction (LVEF)	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Vascular effects	Endothelial function: measurement by Endo-PAT	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Vascular effects	Arterial stiffness: measurement by Endo-PAT	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Vascular effects	Arterial stiffness: measurement by Mobil-O-Graph (pulse wave analysis)	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Vascular effects	Oxygen saturation: transcutaneous oxygen pressure examinations by PRÉCISE 8008, Medicap	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Renal function	Nephrosonography: position, size and surface of kidneys, echogenicity, presence and assessment of cysts and tumors, calcifications, nephroliths	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Renal function	Estimated glomerular Filtration rate (eGFR) using Modification of Diet in Renal Disease (MDRD) formula	Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA
Laboratory parameters in liquor associated with Alzheimer's disease	Measurement of beta-amyloid and tau species concentrations in liquor (optional; only if subjects gave informed consent in lumbar puncture)	Measurement at 2 times: before IA (= baseline) and 12 months after IA

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum analytics	analysis of agonistic autoantibodies against alpha1A adrenoceptor and measurement of different biomarkers, metabolites associated with Alzheimer's disease in blood samples	12 months

Collaborators and Investigators

• Sponsor: University Medicine Greifswald
• Investigators: Principal Investigator: Marcus Dörr, Prof.Dr.med., University Medicine Greifswald

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2016
• Primary Completion (Actual): October 12, 2020
• Study Completion (Actual): October 12, 2020

Study Registration Dates

• First Submitted: November 16, 2016
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Actual): March 9, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Immunoadsorption; ADAsorb apheresis; Globaffin adsorber; Agonistic Autoantibodies; Alzheimer Dementia
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease; Physiological Effects of Drugs; Immunologic Factors; Autoantibodies
• Other Study ID Numbers: 201503IMAD; CIV-16-02-014668 (Other Identifier: EUDAMED-No.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No