Efficacy and Safety of Plasma Exchange With 5% Albutein in Beta-Amyloid Peptide Clearance in Cerebrospinal Fluid

Alzheimer's Disease Clinical Trial

Official title:

A Phase II Study to Evaluate the Efficacy and Safety of Plasma Exchange With 5% Albutein in Beta-Amyloid Peptide Clearance in Cerebrospinal Fluid, and Its Effects in Patients With Mild-Moderate Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00742417
• Other study ID #: IG0602
• Status: Completed
• Phase: Phase 2
• First received: August 25, 2008
• Last updated: March 8, 2012
• Start date: April 2009
• Est. completion date: March 2011

Study information

• Verified date: March 2012
• Source: Grifols Biologicals Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is 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.

Description:

A phase II study comprised of 42 subjects (21 per group) with probable mild to moderate AD will be conducted primarily to determine whether plasma exchange with 5% human albumin is able to modify the concentration of beta-amyloid peptide in cerebrospinal fluid (CSF) in the treatment group of patients with AD.

• There will be two weeks for screening and randomization of both groups (treatment and control).

• The subjects will be randomized in a 1:1 proportion.

• After screening and randomization, treatment will proceed as follows:

• three weeks of intensive treatment with two plasma exchanges per week

• followed by a month and a half of maintenance treatment with one weekly plasma exchange, and

• finally, three months of treatment with one plasma exchange every two weeks.

• The control group will follow the same program, except for the plasma exchanges.

• After the treatment period ends, subjects will be followed-up for a 6-month period of time.

The trial comprises a global multicenter (Spain and US), blind, randomized, controlled design. The trials key coordination is based in Spain where Dr. Boada (see Study Officials/Investigators) is the main study official. A total of 42 subjects are to be enrolled in the study with just 10 subjects in the US.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: March 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

• A diagnosis of AD (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.

Exclusion Criteria:

• Any contraindication for plasma exchange due to behavioral disorders or abnormal coagulation parameters

• Heart diseases, including antecedents of coronary disease and heart failure. 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 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.

• 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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Biological:
• Albutein 5%
18 Plasma Exchanges using Albutein 5% (estimated 3000mL per plasma exchange) or Sham Procedure 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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Grifols, S.A.	Grifols Biologicals Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine whether plasma exchange with 5% human albumin is able to modify the concentration of beta-amyloid peptide in cerebrospinal fluid (CSF) in the treatment group of patients with Alzheimer's disease (AD).		1 year - approx.	No
Secondary	To assess the variations in other parameters (tau protein, beta-secretase, gamma-secretase, nicastrin, etc.). - To determine whether plasma exchange with 5% human albumin is able to modify the plasma concentration of beta-amyloid.		1 year - approx.	No