Multicenter Vitamin E Trial in Aging Persons With Down Syndrome

NCT ID: NCT01594346

Last Updated: 2012-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 349 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-09-30
• Study Completion Date: 2010-04-30

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.

Conditions

Alzheimer's Disease; Down Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sugar Pill

Group Type: PLACEBO_COMPARATOR

Sugar Pill

Intervention Type: DRUG

Alpha-Tocopherol

Group Type: ACTIVE_COMPARATOR

Alpha-Tocopherol

Intervention Type: DRUG

1,000 International Units, two times a day for 36 months

Interventions

Alpha-Tocopherol

1,000 International Units, two times a day for 36 months

Intervention Type: DRUG

Sugar Pill

Intervention Type: DRUG

Other Intervention Names

Vitamin E

Eligibility Criteria

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: collaborator

Bronx Veterans Medical Research Foundation, Inc

OTHER

Sponsor Role: collaborator

New York State Institute for Basic Research

OTHER_GOV

Sponsor Role: lead

Responsible Party

Arthur Dalton

Deputy Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paul S. Aisen, M.D.

Role: STUDY_DIRECTOR

University of California, San Diego

Mary C. Sano, Ph.D.

Role: STUDY_DIRECTOR

Bronx Veterans Medical Research Foundation

Howard F. Andrews, Ph.D.

Role: STUDY_DIRECTOR

New York Psychiatric Institute

Wei-Yann Tsai, Ph.D.

Role: STUDY_DIRECTOR

Columbia University

Other Identifiers

R01AG016381

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCT00056329

Identifier Type: -

Identifier Source: org_study_id