Memory Impairment Study (Mild Cognitive Impairment Study)
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)
2 other identifiers
interventional
N/A
2 countries
72
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Mar 1999
Longer than P75 for phase_3 alzheimer-disease
72 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 1999
CompletedFirst Submitted
Initial submission to the registry
October 29, 1999
CompletedFirst Posted
Study publicly available on registry
November 1, 1999
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2004
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2004
CompletedDecember 11, 2009
June 1, 2009
4.8 years
October 29, 1999
December 10, 2009
Conditions
Keywords
Interventions
Eligibility Criteria
You may qualify if:
- 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.
- +2 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (72)
Barrow Neurological Group
Phoenix, Arizona, 85013, United States
University of Arizona
Tucson, Arizona, 857245023, United States
UC Irvine Institute for Brain Aging and Dementia
Irvine, California, 92697-4285, United States
University of Southern California
Los Angeles, California, 90033, United States
University of California, Los Angeles
Los Angeles, California, 90095-1769, United States
East Bay Institute
Martinez, California, 94553, United States
Sutter Institute for Medical Research
Sacramento, California, 95816, United States
Affiliated Research Instiute
San Diego, California, 92018, United States
University of California, San Diego
San Diego, California, 92093-0949, United States
University of California, San Francisco
San Francisco, California, 94115, United States
Yale University
New Haven, Connecticut, 06520, United States
Baumel-Eisner Neuromedical Institute, Boca Raton
Boca Raton, Florida, 33486, United States
Baumel-Eisner Neuromedical Institute, Ft. Lauderdale
Fort Lauderdale, Florida, 33321, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32225, United States
Wein Center
Miami Beach, Florida, 33140, United States
Baumel-Eisner Neuromedical Institute, MiamiBeach
Miami Beach, Florida, 33154, United States
University of Miami
Port Charlotte, Florida, 33952, United States
University of South Florida
Tampa, Florida, 33612, United States
Premiere Research Institute
West Palm Beach, Florida, 33407, United States
Emory University
Atlanta, Georgia, 30329, United States
Augusta VA Medical Center
Augusta, Georgia, 30904, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rush Presbyterian St. Luke's Medical Center
Chicago, Illinois, 60612, United States
Southern Illinois University
Springfield, Illinois, 62702, United States
Indiana University
Indianapolis, Indiana, 46202-5111, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40536-0230, United States
Johns Hopkins University
Baltimore, Maryland, 21224, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic
Rochester, Minnesota, 55901-0144, United States
Washington University
St Louis, Missouri, 63110, United States
University of Nevada
Las Vegas, Nevada, 89102, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Memory Disorders Institute
Lakehurst, New Jersey, 08733, United States
Princeton Biomedical Research, PA
Princeton, New Jersey, 08540, United States
ClinSearch, Inc.
Summit, New Jersey, 07901, United States
Princeton Biomedical - Toms River
Toms River, New Jersey, 08755, United States
Alzheimer's Research Corp.
West Long Branch, New Jersey, 07764, United States
Univ. of New Mexico
Albuquerque, New Mexico, 89108, United States
Maimonides Medical Center
Brooklyn, New York, 11219, United States
NYU Medical Center
New York, New York, 10016, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
Columbia University
New York, New York, 11032, United States
Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York, 10962, United States
University of Rochester
Rochester, New York, 14620, United States
SUNY Stony Brook
Stony Brook, New York, 11794-8121, United States
Burke Medical Research Institute
White Plains, New York, 10605, United States
Duke University Medical Center
Durham, North Carolina, 27705, United States
University Hospitals of Cleveland
Cleveland, Ohio, 44120-1013, United States
Oregon Health Sciences University
Portland, Oregon, 97201-3098, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
MCP Hahnemann
Philadelphia, Pennsylvania, 19129, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Brown University
Pawtucket, Rhode Island, 02860, United States
Medical University of South Carolina
North Charleston, South Carolina, 29406, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37212-8646, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Southwestern Vermont Medical Center
Bennington, Vermont, 05201, United States
Clinical Neuroscience Research Unit
Burlington, Vermont, 05401, United States
University of Washington
Seattle, Washington, 98108, United States
Marshfield Clinic
Marshfield, Wisconsin, 54449, United States
University of Calgary
Calgary, Alberta, T2N 4N1, Canada
University of British Columbia
Vancouver, British Columbia, V6T 2B5, Canada
Fredericton Medical Clinic
Fredericton, New Brunswick, E3B 6H5, Canada
Geriatric Medicine Research Group
Halifax, Nova Scotia, B3H 2E1, Canada
St. Joseph's Health Center
London, Ontario, N6A 4V2, Canada
Elizabeth Bruyere Centre
Ottawa, Ontario, K1N 5C8, Canada
Sunnybrook Health Science Center
Toronto, Ontario, M4N 3M5, Canada
Jewish General Hospital Memory Clinic
Montreal, Quebec, H3T 1E2, Canada
McGill Centre for Studies in Aging
Verdun, Quebec, H4H 1R3, Canada
Related Publications (9)
Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Neurology. 1998 Jan;50(1):136-45. doi: 10.1212/wnl.50.1.136.
PMID: 9443470BACKGROUNDPetersen RC, Smith GE, Waring SC, Ivnik RJ, Kokmen E, Tangelos EG. Aging, memory, and mild cognitive impairment. Int Psychogeriatr. 1997;9 Suppl 1:65-9. doi: 10.1017/s1041610297004717.
PMID: 9447429BACKGROUNDRubin EH, Morris JC, Grant EA, Vendegna T. Very mild senile dementia of the Alzheimer type. I. Clinical assessment. Arch Neurol. 1989 Apr;46(4):379-82. doi: 10.1001/archneur.1989.00520400033016.
PMID: 2650663BACKGROUNDGrundman M, Petersen RC, Ferris SH, Thomas RG, Aisen PS, Bennett DA, Foster NL, Jack CR Jr, Galasko DR, Doody R, Kaye J, Sano M, Mohs R, Gauthier S, Kim HT, Jin S, Schultz AN, Schafer K, Mulnard R, van Dyck CH, Mintzer J, Zamrini EY, Cahn-Weiner D, Thal LJ; Alzheimer's Disease Cooperative Study. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol. 2004 Jan;61(1):59-66. doi: 10.1001/archneur.61.1.59.
PMID: 14732621RESULTPotashman M, Pang M, Tahir M, Shahraz S, Dichter S, Perneczky R, Nolte S. Psychometric properties of the Alzheimer's Disease Cooperative Study - Activities of Daily Living for Mild Cognitive Impairment (ADCS-MCI-ADL) scale: a post hoc analysis of the ADCS ADC-008 trial. BMC Geriatr. 2023 Mar 6;23(1):124. doi: 10.1186/s12877-022-03527-0.
PMID: 36879199DERIVEDLansdall CJ, McDougall F, Butler LM, Delmar P, Pross N, Qin S, McLeod L, Zhou X, Kerchner GA, Doody RS. Establishing Clinically Meaningful Change on Outcome Assessments Frequently Used in Trials of Mild Cognitive Impairment Due to Alzheimer's Disease. J Prev Alzheimers Dis. 2023;10(1):9-18. doi: 10.14283/jpad.2022.102.
PMID: 36641605DERIVEDDonohue MC, Langford O, Insel PS, van Dyck CH, Petersen RC, Craft S, Sethuraman G, Raman R, Aisen PS; Alzheimer's Disease Neuroimaging Initiative. Natural cubic splines for the analysis of Alzheimer's clinical trials. Pharm Stat. 2023 May-Jun;22(3):508-519. doi: 10.1002/pst.2285. Epub 2023 Jan 10.
PMID: 36627206DERIVEDOxtoby NP, Shand C, Cash DM, Alexander DC, Barkhof F. Targeted Screening for Alzheimer's Disease Clinical Trials Using Data-Driven Disease Progression Models. Front Artif Intell. 2022 May 26;5:660581. doi: 10.3389/frai.2022.660581. eCollection 2022.
PMID: 35719690DERIVEDDeCarli C, Frisoni GB, Clark CM, Harvey D, Grundman M, Petersen RC, Thal LJ, Jin S, Jack CR Jr, Scheltens P; Alzheimer's Disease Cooperative Study Group. Qualitative estimates of medial temporal atrophy as a predictor of progression from mild cognitive impairment to dementia. Arch Neurol. 2007 Jan;64(1):108-15. doi: 10.1001/archneur.64.1.108.
PMID: 17210817DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Leon Thal, MD
Alzheimer's Disease Cooperative Study
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
Study Record Dates
First Submitted
October 29, 1999
First Posted
November 1, 1999
Study Start
March 1, 1999
Primary Completion
January 1, 2004
Study Completion
January 1, 2004
Last Updated
December 11, 2009
Record last verified: 2009-06