Efficacy and Safety of Plasma Exchange With 5% Albumin in Beta-amyloid Peptide Clearance in Cerebral Spinal Fluid

NCT00742417 | Completed Phase 2 Results

• 1 other identifier: IG0602
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of plasma exchange with 5% albumin in beta-amyloid peptide clearance in cerebrospinal fluid, and its effects in patients with mild-moderate Alzheimer's disease.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's; Dementia; Senile; Loss of cognitive abilities; Old age; Elderly; Aging; Albumin; Caregiver; amyloid; beta amyloid; Central Nervous System Diseases; Brain Disease; Mental Disorders; Plasma Exchange

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels.

  Change in levels of Aβ1-42 in CSF in the period between baseline lumbar puncture (before the start of treatment) and lumbar puncture immediately after the end of the last plasma exchange (whenever this may be). Separate assays of Aβ1-42 were performed with Innotest and The Genetics Company commercial kits.

  Baseline and up to week 44

Secondary Outcomes (8)

• P-Tau and Tau CSF Levels Throughout the Study.

  Baseline, week 02, week 08, week 20, week 33 and week 44

• Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company).

  Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44.

• Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company).

  Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44

• Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest).

  Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44.

• Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD)

  Change from baseline at week 44

Study Arms (2)

Albutein 5%

EXPERIMENTAL

Patients allocated to this arm underwent plasma exchange with Albutein 5%.

Biological: Albutein 5%

Control

SHAM COMPARATOR

Other: Control

Interventions

Albutein 5% BIOLOGICAL

18 Plasma Exchanges using Albutein 5%: * three weeks of intensive treatment with two plasma exchanges per week * six weeks of maintenance treatment with one weekly plasma exchange * three months of maintenance treatment with one plasma exchange every two weeks

Albutein 5%

Control OTHER

Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements)

Control

Eligibility Criteria

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

You may qualify if:

• A diagnosis of AD ( National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association \[NINCDS-ADRDA\] criterion), and Mini-mental Status Examination (MMSE) score between ≥18 and ≤26.
• Current stable treatment with acetylcholine esterase inhibitors (AChEIs) for the previous three months.
• A stable care taker must be available, and must attend the patient study visits.
• The patient and a close relative or 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, must be available.

You may not qualify if:

• Any contraindication for plasma exchange due to behavioral disorders or abnormal coagulation parameters
• A history of frequent adverse reactions (serious or otherwise) to blood products.
• Hypersensitivity to albumin or allergies to any of the components of Albutein 5% Human Albumin.
• Plasma creatinine \> 2 mg/dL.
• Uncontrolled high blood pressure.
• Liver cirrhosis or any liver problem with alanine aminotransferase (GPT) \> 2.5 x upper limit of normal (ULN), or bilirubin \> 2 mg/dL.
• Heart diseases, including antecedents of coronary disease and heart failure.
• Difficult venous access precluding plasma exchange.
• Participation in other clinical trials, or the reception 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, toxic habits, 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.
• Prior behavioral disorders requiring pharmacological treatment, including insomnia.

Sponsors & Collaborators

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

Study Sites (4)

Howard University

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

Location

Mid-Atlantic Geriatric/ARC

Whiting, New Jersey, 08759, United States

Location

Fundació ACE

Barcelona, Catalonia, 08028, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, 28007, Spain

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Plaque, Amyloid; Central Nervous System Diseases; Brain Diseases; Mental Disorders

Condition Hierarchy (Ancestors)

Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Mireia Torres
• Organization: Instituto Grifols S.A.

mireia.torres@grifols.com

+34935710500

Study Officials

• Merce Boada, MD

  Fundació ACE

  PRINCIPAL INVESTIGATOR

• Laura Núñez

  Grifols Biologicals, LLC

  STUDY DIRECTOR

• Antonio Paez

  Grifols Biologicals, LLC

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: August 25, 2008
• First Posted: August 27, 2008
• Study Start: July 1, 2007
• Primary Completion: February 1, 2011
• Study Completion: March 1, 2011
• Last Updated: June 14, 2016
• Results First Posted: June 14, 2016

Record last verified: 2016-05

Locations

ES (2); US (2)