Multicenter Vitamin E Trial in Aging Persons With Down Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Down Syndrome; Alzheimer's Disease
• Intervention / Treatment: Drug: Sugar Pill; Drug: Alpha-Tocopherol

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 Type: Interventional
• Enrollment (Actual): 349
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar Pill	Drug: Sugar Pill
Active Comparator: Alpha-Tocopherol	Drug: Alpha-Tocopherol; 1,000 International Units, two times a day for 36 months; Other Names: Vitamin E

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Brief Praxis Test	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: New York State Institute for Basic Research
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of California, San Diego; Columbia University; National Institute on Aging (NIA); National Center for Complementary and Integrative Health (NCCIH); New York State Psychiatric Institute; Bronx Veterans Medical Research Foundation, Inc
• Investigators: Study Director: Paul S. Aisen, M.D., University of California, San Diego; Study Director: Mary C. Sano, Ph.D., Bronx Veterans Medical Research Foundation; Study Director: Howard F. Andrews, Ph.D., New York Psychiatric Institute; Study Director: Wei-Yann Tsai, Ph.D., Columbia University

Study record dates

Study Major Dates

• Study Start: September 1, 2000
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: May 2, 2012
• First Submitted That Met QC Criteria: May 8, 2012
• First Posted (Estimate): May 9, 2012

Study Record Updates

• Last Update Posted (Estimate): May 9, 2012
• Last Update Submitted That Met QC Criteria: May 8, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Vitamin E; Dementia; Aging; cognitive decline; Down syndrome; alpha-tocopherol
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Neurodegenerative Diseases; Intellectual Disability; Dementia; Tauopathies; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Alzheimer Disease; Down Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols; alpha-Tocopherol; Tocotrienols
• Other Study ID Numbers: NCT00056329; R01AG016381 (U.S. NIH Grant/Contract)