Memory Impairment Study (Mild Cognitive Impairment Study)

This study has been completed.
Sponsor:
Collaborator:
Alzheimer's Disease Cooperative Study (ADCS)
Information provided by:
National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:
NCT00000173
First received: October 29, 1999
Last updated: December 10, 2009
Last verified: June 2009
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by National Institute on Aging (NIA):

Study Start Date: March 1999
Study Completion Date: January 2004
Primary Completion Date: January 2004 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   55 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Memory complaints and memory difficulties which are verified by an informant.
  • Abnormal memory function documented by scoring below the education adjusted cutoff on the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale - Revised (the maximum score is 25): a) less than or equal to 8 for 16 or more years of education, b) less than or equal to 4 for 8-15 years of education, c) less than or equal to 2 for 0-7 years of education.
  • Mini-Mental Exam score between 24 and 30 (inclusive) (Exceptions may be made for subjects with less than 8 years of education at the discretion of the project director.).
  • Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5.
  • General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit.
  • No significant cerebrovascular disease: Modified Hachinski score of less than or equal to 4.
  • Age between 55 and 90 (inclusive).
  • Permitted medications stable for at least 1 month prior to screening. In particular: a) Subjects may take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 2 years). b) Estrogen replacement therapy is permissible. c) Ginkgo biloba is permissible, but discouraged.
  • Hamilton Depression rating scale score of less than or equal to 12 on the 17-item scale.
  • Informant is available who has frequent contact with the subject (e.g. an average of 10 hours per week or more), agrees to monitor administration of study drug, observe for adverse events, and accompany the subject to all clinic visits for the duration of the protocol.
  • CT or MRI scans within 12 months prior to screening without evidence of infection, infarction, or other focal lesions and without clinical symptoms suggestive of intervening neurological disease. A lacune in a non-critical brain area which is not believed to contribute to the subject's cognitive impairment is permissible.
  • Adequate visual and auditory acuity to allow neuropsychological testing.
  • Good general health with no additional diseases expected to interfere with the study.
  • Normal B12, RPR, and Thyroid Function Tests or without any clinically significant abnormalities that would be expected to interfere with the study.
  • ECG without clinically significant abnormalities that would be expected to interfere with the study.
  • Subject is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile).
  • Agreement not to take other vitamin supplements (including Vitamin E), multivitamins, other than those provided by the study.

Exclusion Criteria:

  • Any significant neurologic disease other than suspected incipient Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
  • Major depression or another major psychiatric disorder as described in DSM IV within the past 2 years.
  • Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
  • History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).
  • History of schizophrenia (DSM IV criteria).
  • Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol including: a) History of systemic cancer within the last 5 years (non-metastatic skin cancers are acceptable). b) History of myocardial infarction within the past year or unstable or severe cardiovascular disease including angina or CHF with symptoms at rest. c) Clinically significant obstructive pulmonary disease or asthma. d) Clinically significant and unstable gastrointestinal disorder such as ulcer disease or a history of active or occult gastrointestinal bleeding within two years. e) Clinically significant laboratory test abnormalities on the battery of screening tests (hematology, prothrombin time, chemistry, urinalysis, ECG). f) Insulin-requiring diabetes or uncontrolled diabetes mellitus. g) Uncontrolled hypertension (systolic BP greater than 170 or diastolic greater than 100). h) History of clinically significant liver disease, coagulopathy, or vitamin K deficiency within the past 2 years.
  • 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.

  • Vitamin Supplements a) Use of vitamin supplements other than standard multivitamin included as part of the treatment intervention used in this protocol within 2 weeks prior to screening.
  • Any prior use of any FDA approved medications for the treatment of Alzheimer's disease (e.g. tacrine, donepezil, or other newly approved medications).
  • Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening.
  • Subjects who, in the investigator's opinion, will not comply with study procedures.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000173

  Hide Study Locations
Locations
United States, Arizona
Barrow Neurological Group
Phoenix, Arizona, United States, 85013
University of Arizona
Tucson, Arizona, United States, 857245023
United States, California
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 Southern California
Los Angeles, California, United States, 90033
East Bay Institute
Martinez, California, United States, 94553
Sutter Institute for Medical Research
Sacramento, California, United States, 95816
Affiliated Research Instiute
San Diego, California, United States, 92018
University of California, San Diego
San Diego, California, United States, 92093-0949
University of California, San Francisco
San Francisco, California, United States, 94115
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
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32225
Baumel-Eisner Neuromedical Institute, MiamiBeach
Miami Beach, Florida, United States, 33154
Wein Center
Miami Beach, Florida, United States, 33140
University of Miami
Port Charlotte, Florida, United States, 33952
University of South Florida
Tampa, Florida, United States, 33612
Premiere Research Institute
West Palm Beach, Florida, United States, 33407
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30329
Augusta VA Medical Center
Augusta, Georgia, United States, 30904
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
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55901-0144
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
Memory Disorders Institute
Lakehurst, New Jersey, United States, 08733
Princeton Biomedical Research, PA
Princeton, New Jersey, United States, 08540
ClinSearch, Inc.
Summit, New Jersey, United States, 07901
Princeton Biomedical - Toms River
Toms River, New Jersey, United States, 08755
Alzheimer's Research Corp.
West Long Branch, New Jersey, United States, 07764
United States, New Mexico
Univ. of New Mexico
Albuquerque, New Mexico, United States, 89108
United States, New York
Maimonides Medical Center
Brooklyn, New York, United States, 11219
Columbia University
New York, New York, United States, 11032
NYU Medical Center
New York, New York, United States, 10016
Mount Sinai Medical Center
New York, New York, United States, 10029
Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York, United States, 10962
University of Rochester
Rochester, New York, United States, 14620
SUNY Stony Brook
Stony Brook, New York, United States, 11794-8121
Burke Medical Research Institute
White Plains, New York, United States, 10605
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
Southwestern Vermont Medical Center
Bennington, Vermont, United States, 05201
Clinical Neuroscience Research Unit
Burlington, Vermont, United States, 05401
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
St. Joseph's Health Center
London, Ontario, Canada, N6A 4V2
Elizabeth Bruyere Centre
Ottawa, Ontario, Canada, K1N 5C8
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
Sponsors and Collaborators
Alzheimer's Disease Cooperative Study (ADCS)
Investigators
Principal Investigator: Leon Thal, MD Alzheimer's Disease Cooperative Study
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00000173     History of Changes
Other Study ID Numbers: IA0011, 3U01AG10483-08S2
Study First Received: October 29, 1999
Last Updated: December 10, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institute on Aging (NIA):
Mild cognitive impairment
Alzheimer's disease
Memory
Donepezil
Vitamin E
Antioxidants
Cholinergic agents
Cholinesterase inhibitors

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
Mild Cognitive Impairment
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Cholinesterase Inhibitors
Donepezil
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antioxidants
Protective Agents
Micronutrients
Growth Substances
Nootropic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 21, 2014