Memory Impairment Study (Mild Cognitive Impairment Study)
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 3

Summary: 
      The National Institute on Aging (NIA) is launching a nationwide treatment study targeting
      individuals with mild cognitive impairment (MCI), a condition characterized by a memory
      deficit, but not dementia. An NIA-funded study recently confirmed that MCI is different from
      both dementia and normal age-related changes in memory. Accurate and early evaluation and
      treatment of MCI individuals might prevent further cognitive decline, including development
      of Alzheimer's disease (AD).

      The Memory Impairment Study is the first such AD prevention clinical trial carried out by
      NIH, and will be conducted at 65-80 medical research institutions located in the United
      States and Canada. This study will test the usefulness of two drugs to slow or stop the
      conversion from MCI to AD. The trial will evaluate placebo, vitamin E, and donepezil, an
      investigational agent approved by the Food and Drug Administration for another use. Vitamin E
      (alpha-tocopherol) is thought to have antioxidant properties, and was shown in a 1997 study
      to delay important dementia milestones, such as patients' institutionalization or progression
      to severe dementia, by about seven months.
    

Detailed description: 
      This clinical trial will be a multicenter, randomized, double-blind, placebo- controlled,
      parallel-group study of vitamin E and donepezil in 720 subjects with mild cognitive
      impairment (MCI). Subjects will be randomized to one of three treatment groups (240 subjects
      per treatment group): 1) Placebo vitamin E and placebo donepezil plus a multivitamin daily.
      2) Vitamin E (2,000 I) and placebo donepezil plus a multivitamin daily.3) Donepezil (10 mg)
      and placebo vitamin E plus a multivitamin daily.

      The study will be conducted over three years, with clinical evaluations every 3 months for
      the first 6 months and then every 6 months. Subjects randomized to donepezil will start a
      dose of 5 mg daily. Donepezil will be increased to 10 mg after six weeks. Subjects randomized
      to vitamin E will start at 1,000 I daily. The dose of Vitamin E will be increased to 2,000 I
      after six weeks. There will be a 12-month recruitment period. The primary endpoint will be
      time to development of Probable or Possible AD according to NINCDS-ADRDA criteria. Upon
      determination of a clinical diagnosis of AD, documentation will be sent to the ADCS
      Coordinating Center and forwarded to the Central Review Committee for verification. Upon
      verification, of conversion to diagnosis of AD, subjects will stop taking the donepezil study
      medication or its corresponding placebo, without breaking the blind, and will be offered open
      label donepezil at a scheduled visit one month after the prior diagnostic visit. Donepezil
      will be offered to subjects who convert to AD until the subject completes three years from
      the baseline visit. Based on an estimated incidence of AD of 15% per year, the study has 85%
      power to detect a 33% or greater reduction in conversion to AD over 3 years. Secondary
      outcome measures will include change on the Alzheimer's Disease Assessment Scale (ADAS-COG),
      the Neuropsychological Battery, the Mini-Mental State Exam (MMSE), Clinical Dementia Rating
      Scale (CDR), the Global Deterioration Scale (GDS), ADCS- Activities of Daily Living Inventory
      (ADCS-ADL), a Pharmacoeconomics scale, and a Quality of Life scale. Compliance will be
      monitored through the measurement of alpha-tocopherol levels and pill counts at each visit.
    

Intervention name(s): Donepezil; Vitamin E
Intervention type(s): Drug; Drug
Intervention MeSH terms: Vitamin E; Donepezil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Mild cognitive impairment; Alzheimer's disease; Memory; Donepezil; Vitamin E; Antioxidants; Cholinergic agents; Cholinesterase inhibitors