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A Study to Evaluate Albumin and Immunoglobulin in Alzheimer's Disease (AMBAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01561053
Recruitment Status : Active, not recruiting
First Posted : March 22, 2012
Last Update Posted : August 2, 2017
Grifols Biologicals, LLC
Information provided by (Responsible Party):
Grifols Biologicals, LLC ( Instituto Grifols, S.A. )

Brief Summary:
The purpose of this study is to evaluate the changes in the cognitive, functional, behavioral and global domains based on the different applicable psychometric batteries and scales.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Biological: Albumin Biological: Immune globulin Phase 2 Phase 3

Detailed Description:
A clinical trial comprised of 350 subjects with probable mild to moderate Alzheimer's Disease (AD) will be conducted primarily to determine whether plasmapheresis with infusion of human albumin combined with Intravenous immunoglobulin (IVIG) is able to modify patient's cognitive, functional, behavioral and global domains. There will be 3 treatment groups and one control group. The subjects will be randomized in a 1:1:1:1 proportion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Controlled Study To Evaluate The Efficacy and Safety of Short-Term Plasma Exchange Followed by Long-Term Plasmapheresis With Infusion of Human Albumin Combined With Intravenous Immunoglobulin In Patients With Mild-Moderate AD
Study Start Date : March 2012
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Arm Intervention/treatment
Experimental: Treatment group 1
Plasmaexchange with 20% albumin and Immune Globulin (IGIV) high dose
Biological: Albumin
Human albumin 20%
Other Names:
  • Albutein 20%
  • Human Albumin Grifols 20%

Biological: Immune globulin
Intravenous (human) immune globulin 5%
Other Names:
  • Flebogamma DIF 5%
  • flebogammadif 5%

Experimental: Treatment group 2
Plasmaexchange with 20% albumin and Immune Globulin (IGIV) low dose
Biological: Albumin
Human albumin 20%
Other Names:
  • Albutein 20%
  • Human Albumin Grifols 20%

Biological: Immune globulin
Intravenous (human) immune globulin 5%
Other Names:
  • Flebogamma DIF 5%
  • flebogammadif 5%

Experimental: Treatment group 3
Plasmaexchange with 20% albumin (low dose)
Biological: Albumin
Human albumin 20%
Other Names:
  • Albutein 20%
  • Human Albumin Grifols 20%

Biological: Immune globulin
Intravenous (human) immune globulin 5%
Other Names:
  • Flebogamma DIF 5%
  • flebogammadif 5%

No Intervention: Control (sham) group - Simulated procedure
Standard treatment with previously prescribed medications

Primary Outcome Measures :
  1. Cognitive scores (as a change from baseline measurement), measured by ADAS-Cog (Cognitive subscale of the Alzheimer's Disease Assessment Scale) and ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living). [ Time Frame: 14 months ]

Secondary Outcome Measures :
  1. Cognitive, functional and neuropsychiatric scores and overall development as measured by MMSE, NPS battery, ADCS-ADL, NPICDR-Sb, ADCS-CGIC, CSDD, C-SSRS and QoL-AD, RUD-lite. [ Time Frame: 14 months ]
  2. Levels of AB1-40 and AB1-42, T-tau and P-tau in CSF [ Time Frame: 14 months ]
  3. Levels of AB1-40 and AB1-42 in plasma [ Time Frame: 14 months ]
  4. Evaluate the structural changes in volume of the hippocampus, posterior cingulate area, and other associated areas based on neuroimaging study with magnetic resonance imaging (MRI) variation versus baseline. [ Time Frame: 14 months ]
  5. Variation in FDG-PET patterns (flurodeoxyglucose-PET) [ Time Frame: 14 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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

Main Inclusion Criteria:

  1. Males or females between 55-85 years of age at the time of signing of the informed consent document.
  2. A diagnosis of Alzheimer's disease (NINCDS-ADRDA criterion), and MMSE score between >/=18 and </=26.
  3. Current stable treatment with AChEIs and/or memantine for the previous three months.
  4. The patient and a close relative or the legal representative must read the patient information sheet, agree to participation in the trial, and then sign the informed consent document (the patient personally and the close relative/legal representative).
  5. The patient must be able to follow the study protocol, receive the treatment in the established time period, and continue during the follow-up interval.
  6. A brain CAT or MRI study obtained in the 12 months prior to recruitment, showing the absence of cerebrovascular disease, should be available. Nevertheless, it is possible to use the MRI obtained during the screening period to rule out any cerebral vascular disease.
  7. A stable care taker must be available, and must attend the patient study visits.

Main Exclusion Criteria:

  1. Any contraindication for plasma exchange due to behavioral disorders or abnormal coagulation parameters, such as for example:

    • Hypocalcemia (Ca++ < 8.7 mg/dL)
    • Thrombocytopenia (<100,000/µL)
    • Fibrinogen <1.5 g/L)
    • Prothrombin time (Quick) p<60% versus control (INR >1.5)
    • Beta-blocker treatment and bradycardia <60/min)
    • Treatment with angiotension-converting enzyme inhibitors (ACEIs) (increased risk of allergic reactions)
  2. Hemoglobin < 10 mg/dL
  3. Difficult venous access precluding plasma exchange.
  4. A history of frequent adverse reactions (serious or otherwise) to blood products.
  5. Hypersensitivity to albumin or allergies to any of the components of Albutein® 5%.
  6. History of immunoglobulin A (IgA) deficiency.
  7. Known allergies to Flebogamma® DIF components such as sorbitol.
  8. History of thromboembolic complications of intravenous immunoglobulins.
  9. Plasma creatinine > 2 mg/dl.
  10. Uncontrolled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood pressure of 100 mmHg or higher despite treatment during the last 3 months).
  11. Liver cirrhosis or any liver problem with GPT > 2.5 x ULN, or bilirubin > 2 mg/dL.
  12. Heart diseases, as evidenced by myocardial infarction, severe or unstable angina, or heart failure (New York Association Class II, III or IV) in the past 12 months.
  13. Participation in other clinical trials, or the receiption of any other investigational drug in the three months prior to the start of the study.
  14. Any condition complicating adherence to the study protocol (illness with less than one year of expected survival, known drug or alcohol abuse, etc.).
  15. Pregnant or nursing women or women not using effective contraceptive methods for at least one month after plasma exchange.
  16. Fewer than six years of education (exclusion criteria under medical criterion).
  17. Fewer than three months with stable treatment for behavioral disorders or insomnia.

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 identifier (NCT number): NCT01561053

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Sponsors and Collaborators
Instituto Grifols, S.A.
Grifols Biologicals, LLC
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Principal Investigator: Merce Boada Rovira, MD, PhD Fundació ACE. Barcelona. Spain
Study Chair: Antonio Páez, MD Instituto Grifols, S.A.
Study Director: Laura Núñez, BSc Instituto Grifols, S.A.

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Responsible Party: Instituto Grifols, S.A. Identifier: NCT01561053     History of Changes
Other Study ID Numbers: IG1002
First Posted: March 22, 2012    Key Record Dates
Last Update Posted: August 2, 2017
Last Verified: August 2017

Keywords provided by Grifols Biologicals, LLC ( Instituto Grifols, S.A. ):
Alzheimer's disease
AB peptide
Intravenous immune globulin

Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs