Clinical trial NCT01561053: A Study to Evaluate Albumin and Immunoglobulin in Alzheimer's Disease
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 Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease
Amyloid Beta (AB) peptide
Albumin
Intravenous immunoglobulin
IVIG
Lead sponsor: Grifols Biologicals, LLC
Sponsor class: INDUSTRY
Collaborators: name: Grifols Biologicals, LLC
First posted: 2012-03-22
Enrollment: 347
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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.

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 (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.
16. Fewer than six years of education (exclusion criteria under medical criterion).
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.

Primary outcomes:
measure: Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score (Changes From Baseline to 14 Months)
timeFrame: Baseline and 14 months
measure: Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score (Changes From Baseline to 14 Months)
timeFrame: Baseline and 14 Months
Secondary outcomes:
Other outcomes:
measure: ADAS-Cog Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:22-26
timeFrame: Baseline and 14 months
measure: ADCS-ADL Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:22-26
timeFrame: Baseline and 14 months
measure: ADAS-Cog Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:18-21
timeFrame: Baseline and 14 months
measure: ADCS-ADL Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:18-21
timeFrame: Baseline and 14 months
Locations:
city: Sacramento
country: United States
facility: Northern California Research
state: California
city: Denver
country: United States
facility: Mountain View Clinical Research, Inc
state: Colorado
city: Washington
country: United States
facility: Howard University
state: District of Columbia
city: Bradenton
country: United States
facility: Bradenton Research Center, Inc.
state: Florida
city: Deerfield Beach
country: United States
facility: Quantum Laboratories
state: Florida
city: Hialeah
country: United States
facility: Galiz Research, LLC
state: Florida
city: Largo
country: United States
facility: Largo Medical Center
state: Florida
city: Miami
country: United States
facility: L&L Research Choices, Inc
state: Florida
city: Miami
country: United States
facility: Allied Biomedical Research Institute
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research Institute, LLC
state: Florida
city: Ormond Beach
country: United States
facility: Neurology Associates of Osmond Beach
state: Florida
city: Pinellas Park
country: United States
facility: PharmaSeek LLC (DMI Research)
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Savannah
country: United States
facility: RTR Medical Group
state: Georgia
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Manchester
country: United States
facility: Mid-Atlantic Geriatric/ARC
state: New Jersey
city: Mount Arlington
country: United States
facility: The NeuroCognitive Institute
state: New Jersey
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Dayton
country: United States
facility: Neurology Specialists Inc
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Roper St. Francis Healthcare
state: South Carolina
city: Cordova
country: United States
facility: Wesley Neurology Clinic
state: Tennessee
city: Elche
country: Spain
facility: Hospital General de Elche
state: Alicante
city: Elche
country: Spain
facility: Hospital Universitario del Vinalopó
state: Alicante
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital General de Catalunya
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitari Mútua de Terrassa
state: Barcelona
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario Nuestra Señora de Candelaria
state: Canary Islands
city: Getafe
country: Spain
facility: Hospital Universitario de Getafe
state: Madrid
city: Barcelona
country: Spain
facility: Fundació ACE
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Girona
country: Spain
facility: Parc Hospitalari Martí i Julià
city: Lleida
country: Spain
facility: Hospital Universitari de Santa Maria
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Zaragoza
country: Spain
facility: Hospital Viamed Montecanal
Study officials:
affiliation: Fundació ACE. Barcelona. Spain
name: Merce Boada Rovira, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Grifols, S.A.
name: Antonio Páez, MD
role: STUDY_CHAIR
affiliation: Instituto Grifols, S.A.
name: Laura Núñez, BSc
role: STUDY_DIRECTOR
References:
citation: 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.