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.
Multicenter Vitamin E Trial in Aging Persons With Down Syndrome
– Down Syndrome- Alzheimer Disease
Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
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 400 individuals with Down syndrome, 50 years of age and older, will be recruited at approximately 27 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. The primary outcome measure is a brief test of praxis, measuring cognitive functions expressed as performances of simple, short, sequences of voluntary movements in persons with Down syndrome with mild to profound levels of mental retardation. A vitamin E regimen (1,000 international units twice daily, plus a multivitamin) or a placebo will be compared to a multivitamin alone in a two-arm parallel group design. Apoliproprotein 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.
Eligibility & Criteria
Ages Eligible for Study: 50 Years and above, Genders Eligible for Study: Both Criteria Presence of clinically determined Down syndrome (karyotypes optional). Age of 50 years or older at the start of the protocol. 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.