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

Phase 2

Completed

Conditions: Alzheimer's Disease

Interventions: Biological: Albumin 5%
Biological: Albumin 20%
Biological: Immunoglobulin

Registration Number: NCT01561053

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 347

Inclusion Criteria

Males or females between 55-85 years of age at the time of signing of the informed consent document.
A diagnosis of Alzheimer's disease (NINCDS-ADRDA criterion), and mini-mental status examination (MMSE) score between >/=18 and </=26.
Current stable treatment with acetylcholine esterase inhibitors (AChEIs) and/or memantine for the previous three months.
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).
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.
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.
A stable care taker must be available, and must attend the patient study visits.

Main

Exclusion Criteria

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)
Hemoglobin < 10 g/dL
Difficult venous access precluding plasma exchange.
A history of frequent adverse reactions (serious or otherwise) to blood products.
Hypersensitivity to albumin or allergies to any of the components of Albutein.
History of immunoglobulin A (IgA) deficiency.
Known allergies to Flebogamma DIF components such as sorbitol.
History of thromboembolic complications of intravenous immunoglobulins.
Plasma creatinine > 2 mg/dl.
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).
Liver cirrhosis or any liver problem with glutamic pyruvic transaminase (GPT) > 2.5 x upper limit of normal (ULN), or bilirubin > 2 mg/dL.
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.
Participation in other clinical trials, or the receipt of any other investigational drug in the three months prior to the start of the study.
Any condition complicating adherence to the study protocol (illness with less than one year of expected survival, known drug or alcohol abuse, etc.).
Pregnant or nursing women or women not using effective contraceptive methods for at least one month after plasma exchange.
Fewer than six years of education (exclusion criteria under medical criterion).
Less than three months with stable treatment for behavioral disorders or insomnia.
Patients being treated with anticoagulants or antiplatelet therapy (antiaggregants) should not be recruited in the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Albumin + Immunoglobulin	Albumin 5%	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)
High Albumin + Immunoglobulin	Albumin 5%	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)
High Albumin + Immunoglobulin	Albumin 20%	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)
High Albumin + Immunoglobulin	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)
Low Albumin + Immunoglobulin	Albumin 20%	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)
Low Albumin + Immunoglobulin	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)
Low Albumin	Albumin 20%	Therapeutic plasma exchange with albumin 5% (intensive treatment period) + Low volume plasma exchange with low dose of albumin 20% (maintenance treatment period)
Low Albumin	Albumin 5%	Therapeutic plasma exchange with albumin 5% (intensive treatment period) + Low volume plasma exchange with low dose of albumin 20% (maintenance treatment period)

Primary Outcome Measures

Name	Time	Method
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score (Changes From Baseline to 14 Months)	Baseline and 14 months	ADAS-Cog total score as a change from baseline to 14 months The ADAS-Cog Scale is a questionnaire that assesses cognitive performance in 12 different domains. The domains are: word recall, commands, constructional praxis, delayed word-recall task, naming objects/figures, ideational praxis, orientation, word recognition, remembering test instructions, comprehension, word finding difficulty, and spoken language ability. The total score ranges from 0-80 where a higher score indicates more cognitive impairment.
Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score (Changes From Baseline to 14 Months)	Baseline and 14 Months	ADCS-ADL total score as a change from baseline to 14 months The ADCS-ADL comprises 23 questions covering a wide array of activities of daily living. Many of the activities begin with an assessment of whether that activity is relevant and then, if yes, follow with an assessment of the difficulty. The total score over all activities ranges from 0-78 where a higher score indicates more autonomy (better outcome).

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (40): Howard University
🇺🇸
Washington, District of Columbia, United States
Wesley Neurology Clinic
🇺🇸
Cordova, Tennessee, United States
Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Neurology Associates of Osmond Beach
🇺🇸
Ormond Beach, Florida, United States
Hospital General de Elche
🇪🇸
Elche, Alicante, Spain
The NeuroCognitive Institute
🇺🇸
Mount Arlington, New Jersey, United States
Hospital Universitario del Vinalopó
🇪🇸
Elche, Alicante, Spain
Hospital General de Catalunya
🇪🇸
Sant Cugat Del Vallès, Barcelona, Spain
Galiz Research, LLC
🇺🇸
Hialeah, Florida, United States
Bradenton Research Center, Inc.
🇺🇸
Bradenton, Florida, United States
Quantum Laboratories
🇺🇸
Deerfield Beach, 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
RTR Medical Group
🇺🇸
Savannah, Georgia, United States
Largo Medical Center
🇺🇸
Largo, Florida, United States
PharmaSeek LLC (DMI Research)
🇺🇸
Pinellas Park, Florida, United States
iResearch Atlanta, LLC
🇺🇸
Decatur, Georgia, United States
Mid-Atlantic Geriatric/ARC
🇺🇸
Manchester, New Jersey, United States
The Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Neurology Specialists Inc
🇺🇸
Dayton, Ohio, United States
Hospital Universitari Mútua de Terrassa
🇪🇸
Terrassa, Barcelona, Spain
Hospital Universitari de Bellvitge
🇪🇸
Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Nuestra Señora de Candelaria
🇪🇸
Santa Cruz de Tenerife, Canary Islands, Spain
Fundació ACE
🇪🇸
Barcelona, Spain
Hospital Vall d'Hebrón
🇪🇸
Barcelona, Spain
Hospital Universitario de Burgos
🇪🇸
Burgos, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Hospital Universitario y Politécnico La Fe
🇪🇸
Valencia, Spain
Hospital Clínico San Carlos
🇪🇸
Madrid, Spain
Hospital Universitari de Santa Maria
🇪🇸
Lleida, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸
Madrid, Spain
Hospital Viamed Montecanal
🇪🇸
Zaragoza, Spain
Hospital Universitario de Getafe
🇪🇸
Getafe, Madrid, Spain
Mountain View Clinical Research, Inc
🇺🇸
Denver, Colorado, United States
Parc Hospitalari Martí i Julià
🇪🇸
Girona, Spain
Hospital Universitario Doctor Peset
🇪🇸
Valencia, Spain
Northern California Research
🇺🇸
Sacramento, California, United States
Roper St. Francis Healthcare
🇺🇸
Charleston, South Carolina, United States