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

Condition(s) targeted: Alzheimer's Disease

Intervention: Albutein 5% (Biological)

Phase: Phase 2

Status: Completed

Sponsored by: Instituto Grifols, S.A.

Official(s) and/or principal investigator(s):
Merce Boada, MD, Principal Investigator, Affiliation: Fundació ACE - Institut Català de Neurociències Aplicades, Barcelona Spain - mboada@fundacioace.com

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.

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

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

Primary outcome: 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).

Secondary outcome: 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.

Detailed 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.

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

Criteria:

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.

Starting date: April 2009
Last updated: March 8, 2012