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.

Condition	Treatment or Intervention	Phase
Down Syndrome Alzheimer Disease	Drug: Vitamin E  Drug: multivitamin	Phase III

Further Study Details: 

Expected Total Enrollment:  400

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. 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.

Ages Eligible for Study:  50 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

Arthur J Dalton, PhD      718-494-5309    daltonaj@aol.com

California
      University of California, Irvine, Irvine,  California,  92697,  United States; Recruiting
Colorado
      Denver Down Syndrome Clinic, Denver,  Colorado,  80206,  United States; Recruiting
Connecticut
      University of Connecticut Health Center, Farmington,  Connecticut,  06030,  United States; Recruiting
Florida
      Roskamp Institute Memory Clinic, Tampa,  Florida,  33617,  United States; Recruiting
Georgia
      May South, Inc., Atlanta,  Georgia,  30342,  United States; Recruiting
Illinois
      University of Illinois at Chicago, Chicago,  Illinois,  60608,  United States; Recruiting
      Southern Illinois University School of Medicine, Springfield,  Illinois,  62794-9642,  United States; Recruiting
Kentucky
      Third Age, Inc., Lexington,  Kentucky,  40517,  United States; Recruiting
Maryland
      Kennedy Krieger Institute, Baltimore,  Maryland,  21205,  United States; Recruiting
Massachusetts
      McLean Hospital, Belmont,  Massachusetts,  02478,  United States; Recruiting
New Jersey
      Developmental Disabilities Health Alliance, Bloomfield,  New Jersey,  07003,  United States; Recruiting
      Bancroft Neurohealth, Cherry Hill,  New Jersey,  08034,  United States; Recruiting
New York
      Nathan Kline Institute, Orangeburg,  New York,  10962,  United States; Recruiting
      George Jervis Clinic, Staten Island,  New York,  10314,  United States; Recruiting
      Westchester Institute for Human Development, Valhalla,  New York,  10595,  United States; Recruiting
      University at Albany, SUNY, Albany,  New York,  12222,  United States; Recruiting
Australia, New South Wales
      Centre for Developmental Disabilities Studies, Ryde,  New South Wales,  1680,  Australia; Recruiting
Canada, British Columbia
      Down Syndrome Research Foundation, Port Coquitlam,  British Columbia,  V3C 2B2,  Canada; Recruiting
Canada, Ontario
      Surrey Place Centre, Toronto,  Ontario,  M5S 2C2,  Canada; Recruiting
Canada, Saskatchewan
      Saskatoon City Hospital, Saskatoon,  Saskatchewan,  S7K 0M7,  Canada; Recruiting
United Kingdom, England
      Kings College: London, London,  England,  SE5 8AF,  United Kingdom; Recruiting
      Greenfields Monyhull Hospital, Kings Norton, Birmingham,  England,  B30 3QQ,  United Kingdom; Recruiting
      University of Cambridge, Cambridge,  England,  CB2 2AH,  United Kingdom; Recruiting
United Kingdom, Ireland
      Mercer Institute for Research on Ageing, St. James Hospital, Dublin,  Ireland,  8,  United Kingdom; Recruiting

Study chairs or principal investigators

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,  Mount Sinai Medical Center   

Study ID Numbers:  IA0039; NIA Grant AG16381
Record last reviewed:  November 2004
Last Updated:  November 2, 2004
Record first received:  March 10, 2003
ClinicalTrials.gov Identifier:  NCT00056329
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08