Vitamin E in Aging Persons With Down Syndrome

Multicenter Vitamin E Trial in Aging Persons With Down Syndrome

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.

Study Overview

• Status: Unknown
• Conditions: Alzheimer Disease; Down Syndrome
• Intervention / Treatment: Drug: Vitamin E; Drug: multivitamin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Ryde, New South Wales, Australia, 1680
      • Centre for Developmental Disabilities Studies
• Canada
  • British Columbia
    • Port Coquitlam, British Columbia, Canada, V3C 2B2
      • Down Syndrome Research Foundation
  • Ontario
    • Toronto, Ontario, Canada, M5S 2C2
      • Surrey Place Centre
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0M7
      • Saskatoon City Hospital
• United Kingdom
  • England
    • Cambridge, England, United Kingdom, CB2 2AH
      • University of Cambridge
    • Kings Norton, Birmingham, England, United Kingdom, B30 3QQ
      • Greenfields Monyhull Hospital
    • London, England, United Kingdom, SE5 8AF
      • Kings College: London
  • Ireland
    • Dublin, Ireland, United Kingdom, 8
      • Mercer Institute for Research on Ageing, St. James Hospital
• United States
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center
  • Florida
    • Tampa, Florida, United States, 33617
      • Roskamp Institute Memory Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Institute for the Study of Disadvantage and Disability
    • Atlanta, Georgia, United States, 30342
      • May South, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60608
      • University of Illinois at Chicago
    • Springfield, Illinois, United States, 62794-9642
      • Southern Illinois University School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Third Age, Inc.
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Clinical Research Center Of New Jersey
  • New York
    • Albany, New York, United States, 12222
      • University at Albany, SUNY
    • Orangeburg, New York, United States, 10962
      • Nathan Kline Institute
    • Staten Island, New York, United States, 10314
      • George Jervis Clinic
    • Valhalla, New York, United States, 10595
      • Westchester Institute for Human Development
  • Ohio
    • Cleveland, Ohio, United States, 44120
      • University Memory and Aging Center, Case Western Reserve University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: New York State Institute for Basic Research
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute on Aging (NIA); National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Arthur J Dalton, PhD, New York State Institute for Basic Research in Developmental Disabilities; Study Director: Paul S Aisen, MD, Georgetown University; Study Director: Mary C Sano, PhD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Anticipated): May 1, 2012
• Study Completion (Anticipated): May 1, 2012

Study Registration Dates

• First Submitted: March 10, 2003
• First Submitted That Met QC Criteria: March 11, 2003
• First Posted (Estimate): March 12, 2003

Study Record Updates

• Last Update Posted (Estimate): May 4, 2012
• Last Update Submitted That Met QC Criteria: May 2, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Vitamin E; Down Syndrome; Alzheimer disease; Aging Persons
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Neurodegenerative Diseases; Intellectual Disability; Dementia; Tauopathies; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Alzheimer Disease; Down Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols
• Other Study ID Numbers: IA0039; R01AG016381 (U.S. NIH Grant/Contract); NIA Grant AG16381