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

NCT01561053 | Completed Phase 2 Results

• 1 other identifier: IG1002
• Study Type: interventional
• Target: 347
• Locations: 2 countries
• Sites: 40

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.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease; Amyloid Beta (AB) peptide; Albumin; Intravenous immunoglobulin; IVIG

Outcome Measures

Primary Outcomes (2)

• Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score (Changes From Baseline to 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.

  Baseline and 14 months

• Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score (Changes From Baseline to 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).

  Baseline and 14 Months

Other Outcomes (4)

• ADAS-Cog Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:22-26

  Baseline and 14 months

• ADCS-ADL Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:22-26

  Baseline and 14 months

• ADAS-Cog Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:18-21

  Baseline and 14 months

Study Arms (4)

High Albumin + Immunoglobulin

EXPERIMENTAL

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)

Biological: Albumin 5%; Biological: Albumin 20%; Biological: Immunoglobulin

Low Albumin + Immunoglobulin

EXPERIMENTAL

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)

Biological: Albumin 5%; Biological: Albumin 20%; Biological: Immunoglobulin

Low Albumin

EXPERIMENTAL

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

Biological: Albumin 5%; Biological: Albumin 20%

Control (sham) group

NO INTERVENTION

Simulated plasma exchange procedure

Interventions

Albumin 5% BIOLOGICAL

Therapeutic plasma exchange with human albumin 5%

Also known as: Albutein® 5%, Human Albumin Grifols 5%

High Albumin + Immunoglobulin; Low Albumin; Low Albumin + Immunoglobulin

Albumin 20% BIOLOGICAL

Low volume plasma exchange with human albumin 5%

Also known as: Albutein® 20%, Human Albumin Grifols 20%

High Albumin + Immunoglobulin; Low Albumin; Low Albumin + Immunoglobulin

Immunoglobulin BIOLOGICAL

Intravenous human immunoglobulin 5%

Also known as: Flebogamma® 5% DIF

High Albumin + Immunoglobulin; Low Albumin + Immunoglobulin

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto Grifols, S.A.: lead
• Grifols Biologicals, LLC: collaborator

Study Sites (40)

Northern California Research

Sacramento, California, 95821, United States

Location

Mountain View Clinical Research, Inc

Denver, Colorado, 80209, United States

Location

Howard University

Washington D.C., District of Columbia, 20059, United States

Location

Bradenton Research Center, Inc.

Bradenton, Florida, 34205, United States

Location

Quantum Laboratories

Deerfield Beach, Florida, 33064, United States

Location

Galiz Research, LLC

Hialeah, Florida, 33016, United States

Location

Largo Medical Center

Largo, Florida, 33770, United States

Location

L&L Research Choices, Inc

Miami, Florida, 33144, United States

Location

Allied Biomedical Research Institute

Miami, Florida, 33155, United States

Location

Miami Dade Medical Research Institute, LLC

Miami, Florida, 33176, United States

Location

Neurology Associates of Osmond Beach

Ormond Beach, Florida, 32174, United States

Location

PharmaSeek LLC (DMI Research)

Pinellas Park, Florida, 33782, United States

Location

iResearch Atlanta, LLC

Decatur, Georgia, 30030, United States

Location

RTR Medical Group

Savannah, Georgia, 31419, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

The NeuroCognitive Institute

Mount Arlington, New Jersey, 08756, United States

Location

Mid-Atlantic Geriatric/ARC

Paterson, New Jersey, 08759, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Neurology Specialists Inc

Dayton, Ohio, 45417, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Roper St. Francis Healthcare

Charleston, South Carolina, 29401, United States

Location

Wesley Neurology Clinic

Cordova, Tennessee, 38018, United States

Location

Hospital General de Elche

Elche, Alicante, 03203, Spain

Location

Hospital Universitario del Vinalopó

Elche, Alicante, 03293, Spain

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital General de Catalunya

Sant Cugat del Vallès, Barcelona, 08190, Spain

Location

Hospital Universitari Mútua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Hospital Universitario Nuestra Señora de Candelaria

Santa Cruz de Tenerife, Canary Islands, 38010, Spain

Location

Hospital Universitario de Getafe

Getafe, Madrid, 28905, Spain

Location

Fundació ACE

Barcelona, 08028, Spain

Location

Hospital Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario de Burgos

Burgos, 09005, Spain

Location

Parc Hospitalari Martí i Julià

Girona, 17190, Spain

Location

Hospital Universitari de Santa Maria

Lleida, 25198, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Hospital Viamed Montecanal

Zaragoza, 50012, Spain

Location

Related Publications (2)

• 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.

  PMID: 38489186 DERIVED

• 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.

  PMID: 35867135 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid

Interventions

zidovudine 5'-monophosphate-mannose-albumin conjugate; galactosamine-conjugated serum albumin-conjugated-(rhodamine X)20; Immunoglobulins; gamma-Globulins

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: AMBAR clinical manager
• Organization: Grifols

AMBARclinical@grifols.com

+34 935712200

Study Officials

• Merce Boada Rovira, MD, PhD

  Fundació ACE. Barcelona. Spain

  PRINCIPAL INVESTIGATOR

• Antonio Páez, MD

  Instituto Grifols, S.A.

  STUDY CHAIR

• Laura Núñez, BSc

  Instituto Grifols, S.A.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2012
• First Posted: March 22, 2012
• Study Start: April 19, 2012
• Primary Completion: March 6, 2018
• Study Completion: March 6, 2018
• Last Updated: July 31, 2019
• Results First Posted: July 31, 2019

Record last verified: 2019-07

Locations

US (22); ES (18)