Clinical trial NCT01594346: Multicenter Vitamin E Trial in Aging Persons With Down Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Down Syndrome
Keywords: Vitamin E
alpha-tocopherol
cognitive decline
Down syndrome
Aging
Dementia
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)
name: New York State Psychiatric Institute
name: University of California, San Diego
name: Columbia University
name: Bronx Veterans Medical Research Foundation, Inc
First posted: 2012-05-09
Enrollment: 349
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 purpose of this study is to determine the safety and effectiveness of 2,000 international units of Vitamin E (alpha tocopherol)on cognitive function of aging persons with Down syndrome. It is a randomized, double-blind, placebo-controlled trial lasting 36 months. It is expected that Vitamin E will slow the deterioration in cognitive functions associated with Alzheimer disease.

Detailed description: Alzheimer disease (AD) continues to be the most serious health problem faced by aging persons with Down syndrome. AD is also a major public health concern in the aging general population. With increasing life expectancy there will be a dramatic increase in the prevalence of AD cases, which will pose a significant increased burden on the health care system and individual providers of care. Persons with Down syndrome are uniquely vulnerable to a form of Alzheimer disease indistinguishable from the sporadic variety that affects aging individuals from the general population. Oxidative damage is a highly plausible mechanism in the pathogenesis of this disease due to the overexpression of superoxide dismutase, associated with a gene located on chromosome 21, which is present in triplicate in the Down syndrome genotype. For the last six years, we have been conducting a clinical trial to determine the safety and efficacy of the anti-oxidant Vitamin E in slowing the cognitive and functional decline associated with the dementia of AD among individuals with DS. The study is a randomized, double-blind trial, stratified in a two-arm parallel design. The subjects are medically stable individuals who are 50 years of age or older at the time of screening. Among those randomized to the treatment arm, vitamin E is taken in the form of 1000 IU capsules for 36 months. Each subject is evaluated every 6 months for 3 years. The primary outcome is is the Brief Praxis Test (BPT), which is well-suited to quantifying cognitive decline in this population. The target enrollment of 350 persons is estimated to be sufficient to provide adequate statistical power to detect a slowing by one-third in the rate of cognitive decline with vitamin E treatment. The Data and Safety Monitoring Board (DSMB) for this trial includes 4 physicians, and a statistician with expertise in clinical trials. Each DSMB member receives a report on each serious adverse event (SAE) on a flow basis, and statistically summaries of unblinded safety data--including deaths, adverse events and vital signs--prior to each meeting of the DSMB. The most recent DSMB meeting took place on February 23,2010. The timeline for study completion is: recruitment of the study sample (N=350) was completed on 12/31/2008; the final 36-month evaluation will take place in 04/2010; statistical analysis and final report of results is expected to be completed by 12/31/2010.

Eligibility criteria: Inclusion Criteria:

* presence of clinically determined Down syndrome (karyotypes optional)
* appropriately signed and witnessed consent form
* age of 50 years or older at the start of the protocol
* medically stable
* medications stable more than 1 month
* involvement/cooperation of informant/caregiver

Exclusion Criteria:

* medical/neurological condition (other than Alzheimer disease) associated with dementia
* inability to adequately perform the Brief Praxis Test, as demonstrated by a score \<20
* in the presence of dementia, modified Hachinski score \> 4 at Screening Visit
* major depression within 3 months
* history of coagulopathy (inherited or acquired)
* current use of anticoagulants
* use of experimental medications within 2 months
* regular use of vitamin E greater than 50 units per day during the previous 6 months
* allergy to vitamin E

Primary outcomes:
measure: The Brief Praxis Test
timeFrame: 36 months
Secondary outcomes:
measure: The Fuld Object Memory Test
timeFrame: 36 Months
measure: New Dot Test
timeFrame: 36 Months
measure: Orientation Test
timeFrame: 36 Months
measure: Vocabulary Test
timeFrame: 36 Months
measure: Behavior and Function
timeFrame: 36 Months
measure: Clinical Global Impression
timeFrame: 36 Months
measure: Incident Dementia
timeFrame: 36 Months
Other outcomes:
Locations:
Study officials:
affiliation: University of California, San Diego
name: Paul S. Aisen, M.D.
role: STUDY_DIRECTOR
affiliation: Bronx Veterans Medical Research Foundation
name: Mary C. Sano, Ph.D.
role: STUDY_DIRECTOR
affiliation: New York Psychiatric Institute
name: Howard F. Andrews, Ph.D.
role: STUDY_DIRECTOR
affiliation: Columbia University
name: Wei-Yann Tsai, Ph.D.
role: STUDY_DIRECTOR
References: