A Multicenter, Randomized, Controlled Study To Evaluate The Efficacy and Safety of Short-Term Plasma Exchange Followed by Long-Term Plasmapheresis With Infusion of Human Albumin Combined With Intravenous Immunoglobulin In Patients With Mild-Moderate Alzheimer's Disease
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Alzheimer's Disease
- Sponsor
- Instituto Grifols, S.A.
- Enrollment
- 347
- Locations
- 40
- Primary Endpoint
- Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score (Changes From Baseline to 14 Months)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Detailed Description
A clinical trial comprised of 350 subjects with probable mild to moderate Alzheimer's Disease (AD) will be conducted primarily to determine whether plasmapheresis with infusion of human albumin combined with intravenous immunoglobulin (IVIG) is able to modify patient's cognitive, functional, behavioral and global domains. There will be 3 treatment groups and 1 control group. The subjects will be randomized in a 1:1:1:1 proportion.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 \</=
- •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.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score (Changes From Baseline to 14 Months)
Time Frame: Baseline and 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.
Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score (Changes From Baseline to 14 Months)
Time Frame: Baseline and 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).