Clinical trial NCT00742417: Efficacy and Safety of Plasma Exchange With 5% Albumin in Beta-amyloid Peptide Clearance in Cerebral Spinal Fluid
Official title: Phase II Study to Evaluate the Efficacy and Safety of Plasma Exchange With 5% Albumin in Beta-amyloid Peptide Clearance in Cerebral Spinal Fluid, and Its Effects in Patients With Mild-moderate Alzheimer's Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Grifols Biologicals, LLC
Sponsor class: INDUSTRY
Collaborators: name: Grifols Biologicals, LLC
First posted: 2008-08-27
Enrollment: 42
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: A phase II study was 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 patients with AD.

* There was two weeks for screening and randomization of both groups (treatment and control).
* The subjects were randomized in a 1:1 proportion.

After screening and randomization, treatment proceeded 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 followed the same program, except for the plasma exchanges. After the treatment period ended, subjects 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels.
timeFrame: Baseline and up to week 44
Secondary outcomes:
measure: P-Tau and Tau CSF Levels Throughout the Study.
timeFrame: Baseline, week 02, week 08, week 20, week 33 and week 44
measure: Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company).
timeFrame: 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.
measure: Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company).
timeFrame: 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
measure: Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest).
timeFrame: 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.
measure: Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD)
timeFrame: Change from baseline at week 44
measure: Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC).
timeFrame: Change from baseline at week 44
measure: Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline.
timeFrame: Week 00 (baseline), week 20 and week 44
measure: Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT)
timeFrame: End of study
Other outcomes:
Locations:
city: Washington
country: United States
facility: Howard University
state: District of Columbia
city: Manchester Township
country: United States
facility: Mid-Atlantic Geriatric/ARC
state: New Jersey
city: Barcelona
country: Spain
facility: Fundació ACE
state: Catalunya
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
Study officials:
affiliation: Fundació ACE
name: Merce Boada, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Grifols Biologicals, LLC
name: Laura Núñez
role: STUDY_DIRECTOR
affiliation: Grifols Biologicals, LLC
name: Antonio Paez
role: STUDY_CHAIR
References: