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

NCT ID: NCT01561053

Last Updated: 2019-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 347 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-19
• Study Completion Date: 2018-03-06

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.

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 1 control group. The subjects will be randomized in a 1:1:1:1 proportion.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

High Albumin + Immunoglobulin

Therapeutic plasma exchange with albumin 5% (intensive treatment period) + Low volume plasma exchange with high dose of albumin 20% or immunoglobulin 5% (maintenance treatment period)

Group Type: EXPERIMENTAL

Albumin 5%

Intervention Type: BIOLOGICAL

Therapeutic plasma exchange with human albumin 5%

Albumin 20%

Intervention Type: BIOLOGICAL

Low volume plasma exchange with human albumin 5%

Immunoglobulin

Intervention Type: BIOLOGICAL

Intravenous human immunoglobulin 5%

Low Albumin + Immunoglobulin

Therapeutic plasma exchange with albumin 5% (intensive treatment period) + Low volume plasma exchange with low dose of albumin 20% or immunoglobulin 5% (maintenance treatment period)

Group Type: EXPERIMENTAL

Albumin 5%

Intervention Type: BIOLOGICAL

Therapeutic plasma exchange with human albumin 5%

Albumin 20%

Intervention Type: BIOLOGICAL

Low volume plasma exchange with human albumin 5%

Immunoglobulin

Intervention Type: BIOLOGICAL

Intravenous human immunoglobulin 5%

Low Albumin

Therapeutic plasma exchange with albumin 5% (intensive treatment period) + Low volume plasma exchange with low dose of albumin 20% (maintenance treatment period)

Group Type: EXPERIMENTAL

Albumin 5%

Intervention Type: BIOLOGICAL

Therapeutic plasma exchange with human albumin 5%

Albumin 20%

Intervention Type: BIOLOGICAL

Low volume plasma exchange with human albumin 5%

Control (sham) group

Simulated plasma exchange procedure

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Albumin 5%

Therapeutic plasma exchange with human albumin 5%

Intervention Type: BIOLOGICAL

Albumin 20%

Low volume plasma exchange with human albumin 5%

Intervention Type: BIOLOGICAL

Immunoglobulin

Intravenous human immunoglobulin 5%

Intervention Type: BIOLOGICAL

Other Intervention Names

Albutein® 5%; Human Albumin Grifols 5%; Albutein® 20%; Human Albumin Grifols 20%; Flebogamma® 5% DIF

Eligibility Criteria

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 mini-mental status examination (MMSE) score between >/=18 and </=26.

3. Current stable treatment with acetylcholine esterase inhibitors (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 computed axial tomography (CAT) or magnetic resonance imaging (MRI) study, obtained in the 12 months prior to recruitment, showing the absence of cerebrovascular disease, should be available. Nevertheless, it is mandatory to use the MRI obtained during the screening period to rule out any cerebrovascular disease.

7. A stable care taker must be available, and must attend the patient study visits.

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 (international normalized ratio (INR) >1.5)
• Beta-blocker treatment and bradycardia <55/min
• Treatment with angiotension-converting enzyme inhibitors (ACEIs) (increased risk of allergic reactions)

2. Hemoglobin < 10 g/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.

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 glutamic pyruvic transaminase (GPT) > 2.5 x upper limit of normal (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 receipt 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.

17. Less than three months with stable treatment for behavioral disorders or insomnia.

18. Patients being treated with anticoagulants or antiplatelet therapy (antiaggregants) should not be recruited in the study.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grifols Biologicals, LLC

INDUSTRY

Sponsor Role: collaborator

Instituto Grifols, S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Merce Boada Rovira, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fundació ACE. Barcelona. Spain

Antonio Páez, MD

Role: STUDY_CHAIR

Instituto Grifols, S.A.

Laura Núñez, BSc

Role: STUDY_DIRECTOR

Instituto Grifols, S.A.

Locations

Northern California Research

Sacramento, California, United States

Mountain View Clinical Research, Inc

Denver, Colorado, United States

Howard University

Washington D.C., District of Columbia, United States

Bradenton Research Center, Inc.

Bradenton, Florida, United States

Quantum Laboratories

Deerfield Beach, Florida, United States

Galiz Research, LLC

Hialeah, Florida, United States

Largo Medical Center

Largo, Florida, United States

L&L Research Choices, Inc

Miami, Florida, United States

Allied Biomedical Research Institute

Miami, Florida, United States

Miami Dade Medical Research Institute, LLC

Miami, Florida, United States

Neurology Associates of Osmond Beach

Ormond Beach, Florida, United States

PharmaSeek LLC (DMI Research)

Pinellas Park, Florida, United States

iResearch Atlanta, LLC

Decatur, Georgia, United States

RTR Medical Group

Savannah, Georgia, United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

The NeuroCognitive Institute

Mount Arlington, New Jersey, United States

Mid-Atlantic Geriatric/ARC

Paterson, New Jersey, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Neurology Specialists Inc

Dayton, Ohio, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Roper St. Francis Healthcare

Charleston, South Carolina, United States

Wesley Neurology Clinic

Cordova, Tennessee, United States

Hospital General de Elche

Elche, Alicante, Spain

Hospital Universitario del Vinalopó

Elche, Alicante, Spain

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital General de Catalunya

Sant Cugat del Vallès, Barcelona, Spain

Hospital Universitari Mútua de Terrassa

Terrassa, Barcelona, Spain

Hospital Universitario Nuestra Señora de Candelaria

Santa Cruz de Tenerife, Canary Islands, Spain

Hospital Universitario de Getafe

Getafe, Madrid, Spain

Fundació ACE

Barcelona, , Spain

Hospital Vall d'Hebrón

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario de Burgos

Burgos, , Spain

Parc Hospitalari Martí i Julià

Girona, , Spain

Hospital Universitari de Santa Maria

Lleida, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital Universitario Doctor Peset

Valencia, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Hospital Viamed Montecanal

Zaragoza, , Spain

Countries

United States; Spain

References

Podger L, Stewart WF, Serrano D, Lipton RB, Gomez-Ulloa D, Ayasse ND, Barnes FB, Davis EA, Runken MC. Application of a Novel Endpoint Staging Framework: Proof of Concept in the AMBAR Study. J Alzheimers Dis. 2024;98(3):1079-1094. doi: 10.3233/JAD-231197.

Reference Type: DERIVED

PMID: 38489186 (View on PubMed)

Cuberas-Borros G, Roca I, Castell-Conesa J, Nunez L, Boada M, Lopez OL, Grifols C, Barcelo M, Pareto D, Paez A. Neuroimaging analyses from a randomized, controlled study to evaluate plasma exchange with albumin replacement in mild-to-moderate Alzheimer's disease: additional results from the AMBAR study. Eur J Nucl Med Mol Imaging. 2022 Nov;49(13):4589-4600. doi: 10.1007/s00259-022-05915-5. Epub 2022 Jul 22.

Reference Type: DERIVED

PMID: 35867135 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IG1002

Identifier Type: -

Identifier Source: org_study_id