Multicenter Vitamin E Trial in Aging Persons With Down Syndrome

Phase 3

Completed

• Conditions: Alzheimer's Disease; Down Syndrome
• Interventions: Drug: Sugar Pill; Drug: Alpha-Tocopherol

• Registration Number: NCT01594346
• Lead Sponsor: New York State Institute for Basic Research

Brief Summary

The purpose of this study is to determine the safety and effectiveness of 2,000 international units of Vitamin E (alpha tocopherol)on cognitive function of aging persons with Down syndrome. It is a randomized, double-blind, placebo-controlled trial lasting 36 months. It is expected that Vitamin E will slow the deterioration in cognitive functions associated with Alzheimer disease.

Detailed Description

Alzheimer disease (AD) continues to be the most serious health problem faced by aging persons with Down syndrome. AD is also a major public health concern in the aging general population. With increasing life expectancy there will be a dramatic increase in the prevalence of AD cases, which will pose a significant increased burden on the health care system and individual providers of care. Persons with Down syndrome are uniquely vulnerable to a form of Alzheimer disease indistinguishable from the sporadic variety that affects aging individuals from the general population. Oxidative damage is a highly plausible mechanism in the pathogenesis of this disease due to the overexpression of superoxide dismutase, associated with a gene located on chromosome 21, which is present in triplicate in the Down syndrome genotype. For the last six years, we have been conducting a clinical trial to determine the safety and efficacy of the anti-oxidant Vitamin E in slowing the cognitive and functional decline associated with the dementia of AD among individuals with DS. The study is a randomized, double-blind trial, stratified in a two-arm parallel design. The subjects are medically stable individuals who are 50 years of age or older at the time of screening. Among those randomized to the treatment arm, vitamin E is taken in the form of 1000 IU capsules for 36 months. Each subject is evaluated every 6 months for 3 years. The primary outcome is is the Brief Praxis Test (BPT), which is well-suited to quantifying cognitive decline in this population. The target enrollment of 350 persons is estimated to be sufficient to provide adequate statistical power to detect a slowing by one-third in the rate of cognitive decline with vitamin E treatment. The Data and Safety Monitoring Board (DSMB) for this trial includes 4 physicians, and a statistician with expertise in clinical trials. Each DSMB member receives a report on each serious adverse event (SAE) on a flow basis, and statistically summaries of unblinded safety data--including deaths, adverse events and vital signs--prior to each meeting of the DSMB. The most recent DSMB meeting took place on February 23,2010. The timeline for study completion is: recruitment of the study sample (N=350) was completed on 12/31/2008; the final 36-month evaluation will take place in 04/2010; statistical analysis and final report of results is expected to be completed by 12/31/2010.

Study Timeline

• Study Start: 2000-09
• Primary Completion: 2010-04
• Study Completion: 2010-04
• Status Verified: 2012-05
• Study First Submitted: 2012-05-02
• Study First Submitted QC: 2012-05-08
• Last Update Submitted: 2012-05-08
• Study First Posted: 2012-05-09
• Last Update Posted: 2012-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 349

Inclusion Criteria

• presence of clinically determined Down syndrome (karyotypes optional)
• appropriately signed and witnessed consent form
• age of 50 years or older at the start of the protocol
• medically stable
• medications stable more than 1 month
• involvement/cooperation of informant/caregiver

Exclusion Criteria

• medical/neurological condition (other than Alzheimer disease) associated with dementia
• inability to adequately perform the Brief Praxis Test, as demonstrated by a score <20
• in the presence of dementia, modified Hachinski score > 4 at Screening Visit
• major depression within 3 months
• history of coagulopathy (inherited or acquired)
• current use of anticoagulants
• use of experimental medications within 2 months
• regular use of vitamin E greater than 50 units per day during the previous 6 months
• allergy to vitamin E

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sugar Pill	Sugar Pill	-
Alpha-Tocopherol	Alpha-Tocopherol	-

Primary Outcome Measures

Name	Time	Method
The Brief Praxis Test	36 months

Secondary Outcome Measures

Name	Time	Method
The Fuld Object Memory Test	36 Months
New Dot Test	36 Months
Orientation Test	36 Months
Vocabulary Test	36 Months
Behavior and Function	36 Months
Clinical Global Impression	36 Months
Incident Dementia	36 Months