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Immunoadsorption for Treatment of Alzheimer's Disease (IMAD)

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ClinicalTrials.gov Identifier: NCT03132272
Recruitment Status : Recruiting
First Posted : April 27, 2017
Last Update Posted : April 27, 2017
Sponsor:
Information provided by (Responsible Party):
University Medicine Greifswald

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

Condition or disease Intervention/treatment Phase
Alzheimer Dementia Device: Immunoadsorption with Globaffin Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Immunoadsorption for Treatment of Persons With Alzheimer Dementia and Agonistic Autoantibodies Against alpha1A-adrenoceptor (IMAD)
Study Start Date : June 2016
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018


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




Primary Outcome Measures :
  1. Changes in cerebral blood flow, estimated by Arterial Spin Labeling MRI [ 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 ]
    Measurement of cerebral blood flow and evaluation of changes between baseline and condition after intervention over a 12 months period


Secondary Outcome Measures :
  1. Cognition (changes/improvement/impairment) [ Time Frame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA ]
    Measurement by Alzheimer's Disease Assessment Scale (ADAS-cog)

  2. Cognition (changes/improvement/impairment) [ Time Frame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA ]
    Measurement by Mini Mental Status Examination-2 (MMSE)

  3. Cognition (changes/improvement/impairment) [ Time Frame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA ]
    Measurement by California Verbal Learning Test (CVLT)

  4. Cognition (changes/improvement/impairment) [ Time Frame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA ]
    Measurement by Benton Test

  5. Vascular effects [ Time Frame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA ]
    Left ventricular ejection fraction (LVEF)

  6. Vascular effects [ Time Frame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA ]
    Endothelial function: measurement by Endo-PAT

  7. Vascular effects [ Time Frame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA ]
    Arterial stiffness: measurement by Endo-PAT

  8. Vascular effects [ Time Frame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA ]
    Arterial stiffness: measurement by Mobil-O-Graph (pulse wave analysis)

  9. Vascular effects [ Time Frame: 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

  10. Renal function [ Time Frame: Measurement at 4 times: before IA (= baseline), 1 month after IA, 6 months after IA, 12 months after IA ]
    Nephrosonography: position, size and surface of kidneys, echogenicity, presence and assessment of cysts and tumors, calcifications, nephroliths

  11. Renal function [ Time Frame: 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

  12. Laboratory parameters in liquor associated with Alzheimer's disease [ Time Frame: 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)


Other Outcome Measures:
  1. Serum analytics [ Time Frame: 12 months ]
    analysis of agonistic autoantibodies against alpha1A adrenoceptor and measurement of different biomarkers, metabolites associated with Alzheimer's disease in blood samples



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03132272


Contacts
Contact: Sönke Langner, PD Dr. med. 03834 86-22683 ext +49 soenke.langner@uni-greifswald.de
Contact: Bianca Ladwig 03834 86-6962 ext +49 bladwig@uni-greifswald.de

Locations
Germany
University Medicine Greifswald Recruiting
Greifswald, Mecklenburg-Vorpommern, Germany, 17475
Contact: Sönke Langner, PD Dr.med.    03834 86-22683 ext +49    soenke.langner@uni-greifswald.de   
Contact: Bianca Ladwig    03834 86-6962 ext +49    bladwig@uni-greifswald.de   
Sponsors and Collaborators
University Medicine Greifswald
Investigators
Principal Investigator: Sönke Langner, PD Dr. med. University Medicine Greifswald

Responsible Party: University Medicine Greifswald
ClinicalTrials.gov Identifier: NCT03132272     History of Changes
Other Study ID Numbers: 201503IMAD
CIV-16-02-014668 ( Other Identifier: EUDAMED-No. )
First Posted: April 27, 2017    Key Record Dates
Last Update Posted: April 27, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University Medicine Greifswald:
ADAsorb apheresis
Globaffin adsorber
Agonistic Autoantibodies
Immunoadsorption
Alzheimer Dementia

Additional relevant MeSH terms:
Dementia
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Tauopathies
Neurodegenerative Diseases
Autoantibodies
Immunologic Factors
Physiological Effects of Drugs