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

Condition(s) targeted: Alzheimer's Disease

Intervention: Albumin (Biological); Immune globulin (Biological)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Instituto Grifols, S.A.

Official(s) and/or principal investigator(s):
Merce Boada Rovira, MD, PhD, Principal Investigator, Affiliation: Fundació ACE. Barcelona. Spain
Antonio Páez, MD, Study Chair, Affiliation: Instituto Grifols, S.A.
Laura Núñez, BSc, Study Director, Affiliation: Instituto Grifols, S.A.

Overall contact:
Paul J. Pinciaro, PhD, Phone: +1-410-814-7617, Email: paul.pinciaro@grifols.com

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.

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: 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).

Secondary outcome:

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.

Levels of AB1-40 and AB1-42, T-tau and P-tau in CSF

Levels of AB1-40 and AB1-42 in plasma

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.

Variation in FDG-PET patterns (flurodeoxyglucose-PET)

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.

Minimum age: 55 Years. Maximum age: 85 Years. Gender(s): Both.

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 MMSE score between >/=18 and - 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.

Paul J. Pinciaro, PhD, Phone: +1-410-814-7617, Email: paul.pinciaro@grifols.com

Funcació ACE, Barcelona 08028, Spain; Recruiting

Hospital de la Santa Creu i Sant Pau, Barcelona 08041, Spain; Not yet recruiting

Hospital Vall d'Hebron, Barcelona 08035, Spain; Recruiting

Hospital Universitario De Burgos, Burgos 09005, Spain; Recruiting

Parc Hospitalari Marti i Julia, Girona 17190, Spain; Recruiting

Hospital de Santa María, Lleida 25198, Spain; Recruiting

Hospital Clínico San Carlos, Madrid 28040, Spain; Recruiting

Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain; Recruiting

Hospital Universitario Dr. Peset, Valencia 46017, Spain; Recruiting

Hospital Universitario y Politecnico La Fe, Valencia 46026, Spain; Not yet recruiting

Hospital Montecanal, Zaragoza 50012, Spain; Not yet recruiting

Hospital de Vinalopó, Elche, Alicante 03293, Spain; Recruiting

Hospital General de Elche, Elche, Alicante 03203, Spain; Recruiting

Hospital de Torrevieja, Torrevieja, Alicante 03186, Spain; Not yet recruiting

Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona 08907, Spain; Recruiting

Hospital General de Catalunya, San Cugat del Valles, Barcelona 08190, Spain; Recruiting

Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona 08221, Spain; Recruiting

Northern California Research, Sacramento, California 95821, United States; Recruiting

Hospital Ntra. Sra. de la Candelaria, Santa Cruz de Tenerife, Canary Islands 38010, Spain; Recruiting

Mountain View Clinical Research, Inc, Denver, Colorado 80209, United States; Not yet recruiting

Howard University, Washington, District of Columbia 20059, United States; Not yet recruiting

Bradenton Research Center, Inc., Bradenton, Florida 34205, United States; Recruiting

Quantum Laboratories, Deerfield Beach, Florida 33064, United States; Not yet recruiting

Galiz Research, LLC, Hialeah, Florida 33016, United States; Recruiting

Allied Biomedical Research Institute, Miami, Florida 33155, United States; Recruiting

L&L Research Choices, Inc, Miami, Florida 33144, United States; Recruiting

Miami Dade Medical Research Institute, LLC, Miami, Florida 33176, United States; Recruiting

PharmaSeek LLC (DMI Research), Pinellas Park, Florida 33782, United States; Recruiting

iResearch Atlanta, LLC, Decatur, Georgia 30030, United States; Recruiting

RTR Medical Group, Savannah, Georgia 31419, United States; Recruiting

Hospital Universitario de Getafe, Getafe, Madrid 28905, Spain; Not yet recruiting

Mid-Atlantic Geriatric/ARC, Manchester Township, New Jersey 08759, United States; Recruiting

The NeuroCognitive Institute, Mt. Arlington, New Jersey 08756, United States; Not yet recruiting

The Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, United States; Recruiting

Roper St. Francis Healthcare, Charleston, South Carolina 29401, United States; Not yet recruiting

Wesley Neurology Clinic, Cordova, Tennessee 38018, United States; Not yet recruiting

Starting date: March 2012
Last updated: June 15, 2015