Vitamin E in Aging Persons With Down Syndrome

Study Overview
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Brief Summary
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The goal of this study is to determine the safety and efficacy of the administration of vitamin E, which has been shown to delay the progression of Alzheimer's disease, in slowing the rate of cognitive/functional decline in older persons with Down syndrome.

Detailed Description
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The growing success of therapeutic interventions (including the antioxidant Vitamin E) for Alzheimer's disease in the general population requires a solution to the methodological problems so that therapeutic trials can be conducted in the aging population with Down syndrome which will ultimately improve their quality of life as well as that of their families and caregivers. The experience gained in this trial will be useful to the design of appropriate cognitive measures of Alzheimer's disease in persons with Down syndrome in subsequent trials. The goal of this international three-year study is to determine whether the administration of vitamin E, which has been shown to delay the progression of Alzheimer's disease, will slow the rate of cognitive/functional decline in persons age 50 or older with Down syndrome. Persons with Down syndrome functioning at all levels of intellectual disability will be eligible. Men and women of approximately equal numbers and people from minorities and ethnic groups other than Caucasian will be included. A total of 350 individuals with Down syndrome, 50 years of age and older, have been recruited at approximately 21 trial sites. The study is a randomized, double-blind, placebo-controlled, parallel group design with stratification by geographic site and presence of Alzheimer disease according to DSM-IV (American Psychiatric Association) criteria for diagnosing this disease. Apolipoprotein E (Apo E) genotype will be determined at the screening visit to allow secondary analyses of the impact of Apo E genotype (that may influence Alzheimer's disease risk) on outcome measures and the response to treatment. DNA specimens will also be stored for possible future genetic analyses, with trial sites allowing for non-participation in this procedure. Visits will occur at baseline and then at 6 monthly intervals, with each visit including interval medical history, current and interval medications, side effects checklist, adverse events, pill count, institutionalization status, cognitive, functional, and behavioral measures, and DSM-IV diagnostic assessment for Alzheimer's disease.

Official Title
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Multicenter Vitamin E Trial in Aging Persons With Down Syndrome

Conditions
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Down Syndrome, Alzheimer Disease

Intervention / Treatment
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* Drug: Vitamin E
* Drug: multivitamin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of clinically determined Down syndrome (karyotypes optional). Medically stable. Medications stable over 3 months. Appropriately signed and witnessed consent form. Involvement/cooperation of informant/caregiver. Exclusion Criteria: Medical/neurological condition (other than Alzheimer's disease) associated with dementia. Brief Praxis Test score <20. Modified Hachinski score >4. Major depression within 3 months. History of any disorder of blood coagulation (inherited or acquired). Current use of anti-coagulants. Use of experimental medications within 3 months. Regular use of vitamin E greater than 50 units per day during the previous 6 months.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>vitamin E plus multivitamin | Drug: Vitamin E<br>* 1,000 international units twice daily for three years<br>* Other names: tocopherol;Drug: multivitamin<br>* once daily for three years<br>|
| Placebo Comparator: 2<br>placebo with multivitamin | Drug: multivitamin<br>* once daily for three years<br>Drug: Placebo<br>* Placebo twice daily for three years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Praxis Test, measuring cognitive functions expressed as performances of simple, short, sequences of voluntary movements |  | Screening, Baseline, every 6 months for 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fuld Object Memory Test (Modified), New Dot Test, Orientation Test, Vocabulary Test, Behavior & Function Down Syndrome Rating Scale, Clinical Global Impression of Change (CGI-C) |  | Screening, Baseline, and every 6 months for 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aging Persons, Down Syndrome, Vitamin E, Alzheimer disease