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| Sponsor: | National Institute on Aging (NIA) |
|---|---|
| Collaborator: |
Alzheimer's Disease Cooperative Study (ADCS) |
| Information provided by: | National Institute on Aging (NIA) |
| ClinicalTrials.gov Identifier: | NCT00000173 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Alzheimer Disease |
Drug: Donepezil Drug: Vitamin E |
Phase III |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study |
| Official Title: | A Randomized, Double-Blind, Placebo-Controlled Trial of Vitamin E and Donepezil HCL (Aricept) to Delay Clinical Progression From Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD) |
| Study Start Date: | March 1999 |
| Estimated Study Completion Date: | January 2004 |
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.
Eligibility| Ages Eligible for Study: | 55 Years to 90 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Medications a) Use of centrally active beta-blockers, narcotics, methyldopa and clonidine within 4 weeks prior to screening. b) Use of anti-Parkinsonian medications (e.g. Sinemet, amantadine, bromocriptine, pergolide and selegiline) within 2 months prior to screening. c) Use of neuroleptics or narcotic analgesics within 4 weeks prior to screening. d) Use of long-acting benzodiazepines or barbituates within 4 weeks prior to screening. e) Use of short-acting anxiolytics or sedative hypnotics more frequently than 2 times per week within 4 weeks prior to screening (note: sedative agents should not be used within 72 hours of screening).
f) Initiation or change in dose of an antidepressant lacking significant cholinergic side effects within the 4 weeks prior to screening (use of stable doses of antidepressants for at least 4 weeks prior to screening is acceptable). g) Use of systemic corticosteroids within 3 months prior to screening. h) Medications with significant cholinergic or anticholinergic side effects (e.g. pyridostigmine, tricyclic antidepressants, meclizine, and oxybutynin) within 4 weeks prior to screening. i) Use of anti-convulsants (e.g. Phenytoin, Phenobarbital, Carbamazepine) within 2 months prior to screening. j) Use of warfarin (Coumadin) within 4 weeks prior to screening.
Contacts and Locations
Hide Study Locations| United States, Arizona | |
| Barrow Neurological Group | |
| Phoenix, Arizona, United States, 85013 | |
| University of Arizona | |
| Tucson, Arizona, United States, 857245023 | |
| United States, California | |
| Affiliated Research Instiute | |
| San Diego, California, United States, 92018 | |
| East Bay Institute | |
| Martinez, California, United States, 94553 | |
| University of California, San Francisco | |
| San Francisco, California, United States, 94115 | |
| UC Irvine Institute for Brain Aging and Dementia | |
| Irvine, California, United States, 92697-4285 | |
| University of California, Los Angeles | |
| Los Angeles, California, United States, 90095-1769 | |
| University of California, San Diego | |
| San Diego, California, United States, 92093-0949 | |
| Sutter Institute for Medical Research | |
| Sacramento, California, United States, 95816 | |
| University of Southern California | |
| Los Angeles, California, United States, 90033 | |
| United States, Connecticut | |
| Yale University | |
| New Haven, Connecticut, United States, 06520 | |
| United States, Florida | |
| Baumel-Eisner Neuromedical Institute, Boca Raton | |
| Boca Raton, Florida, United States, 33486 | |
| Baumel-Eisner Neuromedical Institute, Ft. Lauderdale | |
| Ft. Lauderdale, Florida, United States, 33321 | |
| Baumel-Eisner Neuromedical Institute, MiamiBeach | |
| Miami Beach, Florida, United States, 33154 | |
| University of South Florida | |
| Tampa, Florida, United States, 33612 | |
| Premiere Research Institute | |
| West Palm Beach, Florida, United States, 33407 | |
| University of Miami | |
| Port Charlotte, Florida, United States, 33952 | |
| Mayo Clinic Jacksonville | |
| Jacksonville, Florida, United States, 32225 | |
| Wein Center | |
| Miami Beach, Florida, United States, 33140 | |
| United States, Georgia | |
| Augusta VA Medical Center | |
| Augusta, Georgia, United States, 30904 | |
| Emory University | |
| Atlanta, Georgia, United States, 30329 | |
| United States, Illinois | |
| Northwestern University | |
| Chicago, Illinois, United States, 60611 | |
| Rush Presbyterian St. Luke's Medical Center | |
| Chicago, Illinois, United States, 60612 | |
| Southern Illinois University | |
| Springfield, Illinois, United States, 62702 | |
| United States, Indiana | |
| Indiana University | |
| Indianapolis, Indiana, United States, 46202-5111 | |
| United States, Kansas | |
| University of Kansas Medical Center | |
| Kansas City, Kansas, United States, 66160 | |
| United States, Kentucky | |
| University of Kentucky | |
| Lexington, Kentucky, United States, 40536-0230 | |
| United States, Maryland | |
| Johns Hopkins University | |
| Baltimore, Maryland, United States, 21224 | |
| United States, Massachusetts | |
| Massachusetts General Hospital | |
| Boston, Massachusetts, United States, 02114 | |
| United States, Michigan | |
| University of Michigan | |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55901-0144 | |
| University of Minnesota | |
| Minneapolis, Minnesota, United States, 55455 | |
| United States, Missouri | |
| Washington University | |
| St. Louis, Missouri, United States, 63110 | |
| United States, Nevada | |
| University of Nevada | |
| Las Vegas, Nevada, United States, 89102 | |
| United States, New Hampshire | |
| Dartmouth Hitchcock Medical Center | |
| Lebanon, New Hampshire, United States, 03756 | |
| United States, New Jersey | |
| Alzheimer's Research Corp. | |
| West Long Branch, New Jersey, United States, 07764 | |
| ClinSearch, Inc. | |
| Summit, New Jersey, United States, 07901 | |
| Memory Disorders Institute | |
| Lakehurst, New Jersey, United States, 08733 | |
| Princeton Biomedical Research, PA | |
| Princeton, New Jersey, United States, 08540 | |
| Princeton Biomedical - Toms River | |
| Toms River, New Jersey, United States, 08755 | |
| United States, New Mexico | |
| Univ. of New Mexico | |
| Albuquerque, New Mexico, United States, 89108 | |
| United States, New York | |
| Mount Sinai Medical Center | |
| New York, New York, United States, 10029 | |
| Columbia University | |
| New York, New York, United States, 11032 | |
| Maimonides Medical Center | |
| Brooklyn, New York, United States, 11219 | |
| Burke Medical Research Institute | |
| White Plains, New York, United States, 10605 | |
| Nathan S. Kline Institute for Psychiatric Research | |
| Orangeburg, New York, United States, 10962 | |
| NYU Medical Center | |
| New York, New York, United States, 10016 | |
| SUNY Stony Brook | |
| Stony Brook, New York, United States, 11794-8121 | |
| University of Rochester | |
| Rochester, New York, United States, 14620 | |
| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27705 | |
| United States, Ohio | |
| University Hospitals of Cleveland | |
| Cleveland, Ohio, United States, 44120-1013 | |
| United States, Oregon | |
| Oregon Health Sciences University | |
| Portland, Oregon, United States, 97201-3098 | |
| United States, Pennsylvania | |
| MCP Hahnemann | |
| Philadelphia, Pennsylvania, United States, 19129 | |
| University of Pennsylvania | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| University of Pittsburgh | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| United States, Rhode Island | |
| Brown University | |
| Pawtucket, Rhode Island, United States, 02860 | |
| United States, South Carolina | |
| Medical University of South Carolina | |
| North Charleston, South Carolina, United States, 29406 | |
| United States, Tennessee | |
| Vanderbilt University Medical Center | |
| Nashville, Tennessee, United States, 37212-8646 | |
| United States, Texas | |
| Baylor College of Medicine | |
| Houston, Texas, United States, 77030 | |
| United States, Vermont | |
| Clinical Neuroscience Research Unit | |
| Burlington, Vermont, United States, 05401 | |
| Southwestern Vermont Medical Center | |
| Bennington, Vermont, United States, 05201 | |
| United States, Washington | |
| University of Washington | |
| Seattle, Washington, United States, 98108 | |
| United States, Wisconsin | |
| Marshfield Clinic | |
| Marshfield, Wisconsin, United States, 54449 | |
| Canada, Alberta | |
| University of Calgary | |
| Calgary, Alberta, Canada, T2N 4N1 | |
| Canada, British Columbia | |
| University of British Columbia | |
| Vancouver, British Columbia, Canada, V6T 2B5 | |
| Canada, New Brunswick | |
| Fredericton Medical Clinic | |
| Fredericton, New Brunswick, Canada, E3B 6H5 | |
| Canada, Nova Scotia | |
| Geriatric Medicine Research Group | |
| Halifax, Nova Scotia, Canada, B3H 2E1 | |
| Canada, Ontario | |
| Elizabeth Bruyere Centre | |
| Ottawa, Ontario, Canada, K1N 5C8 | |
| St. Joseph's Health Center | |
| London, Ontario, Canada, N6A 4V2 | |
| Sunnybrook Health Science Center | |
| Toronto, Ontario, Canada, M4N 3M5 | |
| Canada, Quebec | |
| Jewish General Hospital Memory Clinic | |
| Montreal, Quebec, Canada, H3T 1E2 | |
| McGill Centre for Studies in Aging | |
| Verdun, Quebec, Canada, H4H 1R3 | |
| Principal Investigator: | Leon Thal, MD | Alzheimer's Disease Cooperative Study |
More Information
| Study ID Numbers: | IA0011, 3U01AG10483-08S2 |
| Study First Received: | October 29, 1999 |
| Last Updated: | June 10, 2009 |
| ClinicalTrials.gov Identifier: | NCT00000173 History of Changes |
| Health Authority: | United States: Federal Government |
|
Mild cognitive impairment Alzheimer's disease Memory Donepezil |
Vitamin E Antioxidants Cholinergic agents Cholinesterase inhibitors |
|
Neurotransmitter Agents Antioxidants Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Neurodegenerative Diseases Brain Diseases Cholinergic Agents Tocopherols Mental Disorders Therapeutic Uses Vitamins Donepezil Tocotrienols Micronutrients Dementia |
Nootropic Agents Tocopherol acetate Growth Substances Nervous System Diseases Alzheimer Disease Central Nervous System Diseases Enzyme Inhibitors Protective Agents Cognition Disorders Pharmacologic Actions Alpha-Tocopherol Cholinesterase Inhibitors Vitamin E Delirium, Dementia, Amnestic, Cognitive Disorders Tauopathies |