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Immunoadsorption for Treatment of Alzheimer's Disease (IMAD)

Primary Purpose

Alzheimer Dementia

Status

Terminated

Phase

Not Applicable

Locations

Germany

Study Type

Interventional

Intervention

Immunoadsorption with Globaffin

About this trial

This is an interventional treatment trial for Alzheimer Dementia focused on measuring ADAsorb apheresis, Globaffin adsorber, Agonistic Autoantibodies, Immunoadsorption, Alzheimer Dementia

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Medicine Greifswald

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Immunoadsorption with Globaffin for Alzheimer Dementia

Arm Description

Immunoadsorption with Globaffin

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Cognition (changes/improvement/impairment)

Measurement by Alzheimer's Disease Assessment Scale (ADAS-cog)

Cognition (changes/improvement/impairment)

Measurement by Mini Mental Status Examination-2 (MMSE)

Cognition (changes/improvement/impairment)

Measurement by California Verbal Learning Test (CVLT)

Cognition (changes/improvement/impairment)

Measurement by Benton Test

Vascular effects

Left ventricular ejection fraction (LVEF)

Vascular effects

Endothelial function: measurement by Endo-PAT

Vascular effects

Arterial stiffness: measurement by Endo-PAT

Vascular effects

Arterial stiffness: measurement by Mobil-O-Graph (pulse wave analysis)

Vascular effects

Oxygen saturation: transcutaneous oxygen pressure examinations by PRÉCISE 8008, Medicap

Renal function

Nephrosonography: position, size and surface of kidneys, echogenicity, presence and assessment of cysts and tumors, calcifications, nephroliths

Renal function

Estimated glomerular Filtration rate (eGFR) using Modification of Diet in Renal Disease (MDRD) formula

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)

Full Information

NCT ID

NCT03132272

First Posted

November 16, 2016

Last Updated

March 4, 2021

Sponsor

University Medicine Greifswald

1. Study Identification

Unique Protocol Identification Number

NCT03132272

Brief Title

Immunoadsorption for Treatment of Alzheimer's Disease

Acronym

IMAD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Terminated

Why Stopped

slow recruiting, difficulties in finding eligible patients

Study Start Date

September 15, 2016 (Actual)

Primary Completion Date

October 12, 2020 (Actual)

Study Completion Date

October 12, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Medicine Greifswald

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Dementia

Keywords

ADAsorb apheresis, Globaffin adsorber, Agonistic Autoantibodies, Immunoadsorption, Alzheimer Dementia

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Immunoadsorption with Globaffin for Alzheimer Dementia

Arm Type

Experimental

Arm Description

Immunoadsorption with Globaffin

Intervention Type

Device

Intervention Name(s)

Immunoadsorption with Globaffin

Other Intervention Name(s)

agonistic autoantibodies, alpha1A-adrenoceptor, Globaffin adsorber columns, ADAsorb apheresis

Intervention Description

Immunoadsorption for treatment of persons with Alzheimer Dementia

Primary Outcome Measure Information:

Title

Changes in cerebral blood flow, estimated by Arterial Spin Labeling MRI

Description

Measurement of cerebral blood flow and evaluation of changes between baseline and condition after intervention over a 12 months period

Time Frame

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 Measure Information:

Title

Cognition (changes/improvement/impairment)

Description

Measurement by Alzheimer's Disease Assessment Scale (ADAS-cog)

Time Frame