Multicenter Vitamin E Trial in Aging Persons With Down Syndrome

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease; Down Syndrome	Drug: Alpha-Tocopherol; Drug: Sugar Pill	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	349 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Study Start Date :	September 2000
Actual Primary Completion Date :	April 2010
Actual Study Completion Date :	April 2010

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: Vitamin E

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. The Brief Praxis Test [ Time Frame: 36 months ]

Secondary Outcome Measures :

1. The Fuld Object Memory Test [ Time Frame: 36 Months ]
2. New Dot Test [ Time Frame: 36 Months ]
3. Orientation Test [ Time Frame: 36 Months ]
4. Vocabulary Test [ Time Frame: 36 Months ]
5. Behavior and Function [ Time Frame: 36 Months ]
6. Clinical Global Impression [ Time Frame: 36 Months ]
7. Incident Dementia [ Time Frame: 36 Months ]

Eligibility Criteria

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Ages Eligible for Study:	50 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Sponsors and Collaborators

New York State Institute for Basic Research

National Institute on Aging (NIA)

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

National Center for Complementary and Integrative Health (NCCIH)

New York State Psychiatric Institute

University of California, San Diego

Columbia University

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Arthur Dalton, Deputy Director, New York State Institute for Basic Research
ClinicalTrials.gov Identifier:	NCT01594346 History of Changes
Other Study ID Numbers:	R01AG016381 ( U.S. NIH Grant/Contract )
First Posted:	May 9, 2012
Last Update Posted:	May 9, 2012
Last Verified:	May 2012

Keywords provided by Arthur Dalton, New York State Institute for Basic Research:

Vitamin E; alpha-tocopherol; cognitive decline	Down syndrome; Aging; Dementia

Additional relevant MeSH terms:

Syndrome; Alzheimer Disease; Down Syndrome; Disease; Pathologic Processes; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Intellectual Disability; Neurobehavioral Manifestations	Neurologic Manifestations; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Vitamins; Vitamin E; Tocopherols; Tocotrienols; alpha-Tocopherol; Micronutrients; Growth Substances; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action