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.
Full Title of Study: “Multicenter Vitamin E Trial in Aging Persons With Down Syndrome”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Study Primary Completion Date: May 2012
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.
- Drug: Vitamin E
- 1,000 international units twice daily for three years
- Drug: multivitamin
- once daily for three years
- Drug: Placebo
- Placebo twice daily for three years
Arms, Groups and Cohorts
- Experimental: 1
- vitamin E plus multivitamin
- Placebo Comparator: 2
- placebo with multivitamin
Clinical Trial Outcome Measures
- Brief Praxis Test, measuring cognitive functions expressed as performances of simple, short, sequences of voluntary movements
- Time Frame: Screening, Baseline, every 6 months for 36 months
- 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)
- Time Frame: Screening, Baseline, and every 6 months for 36 months
Participating in This Clinical Trial
- 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.
- 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.
Gender Eligibility: All
Minimum Age: 50 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- New York State Institute for Basic Research
- National Institute on Aging (NIA)
- Provider of Information About this Clinical Study
- Principal Investigator: Arthur Dalton, Deputy Director – New York State Institute for Basic Research
- Overall Official(s)
- Arthur J Dalton, PhD, Principal Investigator, New York State Institute for Basic Research in Developmental Disabilities
- Paul S Aisen, MD, Study Director, Georgetown University
- Mary C Sano, PhD, Study Director, Icahn School of Medicine at Mount Sinai
Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997 Apr 24;336(17):1216-22.
Aisen PS, Davis KL. The search for disease-modifying treatment for Alzheimer's disease. Neurology. 1997 May;48(5 Suppl 6):S35-41. Review.
Aylward EH, Burt DB, Thorpe LU, Lai F, Dalton A. Diagnosis of dementia in individuals with intellectual disability. J Intellect Disabil Res. 1997 Apr;41 ( Pt 2):152-64.
Dalton, AJ, Mehta, PD, Fedor, BL, Patti, PJ: Cognitive changes in memory precede those in praxis in aging persons with Down syndrome. Journal of Intellectual and Developmental Disability 24(2):169-187,1999.
Citations Reporting on Results
Sano M, Aisen PS, Dalton AJ, Andrews HF, Tsai W-Y, and the International Down Syndrome Alzheimer Disease Consortium. Assessment of aging individuals with Down syndrome in clinical trials: results of baseline measures. Journal of Policy and Practice in Intellectual Disabilities. 2005 2(2):126-138.
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