Clinical trial NCT00056329: Vitamin E in Aging Persons With Down Syndrome
Official title: Multicenter Vitamin E Trial in Aging Persons With Down Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Down Syndrome
Alzheimer Disease
Keywords: Aging Persons
Down Syndrome
Vitamin E
Alzheimer disease
Lead sponsor: New York State Institute for Basic Research
Sponsor class: OTHER_GOV
Collaborators: name: National Institute on Aging (NIA)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2003-03-12
Enrollment: 350
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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.

Primary outcomes:
measure: Brief Praxis Test, measuring cognitive functions expressed as performances of simple, short, sequences of voluntary movements
timeFrame: Screening, Baseline, every 6 months for 36 months
Secondary outcomes:
measure: 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)
timeFrame: Screening, Baseline, and every 6 months for 36 months
Other outcomes:
Locations:
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Tampa
country: United States
facility: Roskamp Institute Memory Clinic
state: Florida
city: Atlanta
country: United States
facility: Institute for the Study of Disadvantage and Disability
state: Georgia
city: Atlanta
country: United States
facility: May South, Inc.
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Lexington
country: United States
facility: Third Age, Inc.
state: Kentucky
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
city: Voorhees
country: United States
facility: Clinical Research Center of New Jersey
state: New Jersey
city: Albany
country: United States
facility: University at Albany, SUNY
state: New York
city: Orangeburg
country: United States
facility: Nathan Kline Institute
state: New York
city: Staten Island
country: United States
facility: George Jervis Clinic
state: New York
city: Valhalla
country: United States
facility: Westchester Institute for Human Development
state: New York
city: Cleveland
country: United States
facility: University Memory and Aging Center, Case Western Reserve University
state: Ohio
city: Ryde
country: Australia
facility: Centre for Developmental Disabilities Studies
state: New South Wales
city: Port Coquitlam
country: Canada
facility: Down Syndrome Research Foundation
state: British Columbia
city: Toronto
country: Canada
facility: Surrey Place Centre
state: Ontario
city: Saskatoon
country: Canada
facility: Saskatoon City Hospital
state: Saskatchewan
city: Cambridge
country: United Kingdom
facility: University of Cambridge
state: England
city: Kings Norton, Birmingham
country: United Kingdom
facility: Greenfields Monyhull Hospital
state: England
city: London
country: United Kingdom
facility: Kings College: London
state: England
city: Dublin
country: United Kingdom
facility: Mercer Institute for Research on Ageing, St. James Hospital
state: Ireland
Study officials:
affiliation: New York State Institute for Basic Research in Developmental Disabilities
name: Arthur J Dalton, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Georgetown University
name: Paul S Aisen, MD
role: STUDY_DIRECTOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Mary C Sano, PhD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1056/NEJM199704243361704.
citation: Aisen PS, Davis KL. The search for disease-modifying treatment for Alzheimer's disease. Neurology. 1997 May;48(5 Suppl 6):S35-41. doi: 10.1212/wnl.48.5_suppl_6.35s.
citation: 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. doi: 10.1111/j.1365-2788.1997.tb00692.x.
citation: 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.
citation: 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.