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Alzheimer DiseasePhase 3NCT00000173

Memory Impairment Study (Mild Cognitive Impairment Study)

A Phase 3 study testing Donepezil and Vitamin E in people with Alzheimer Disease, run by National Institute on Aging (NIA) at 72 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 55 to 90 years
Conditions the study is for
Alzheimer Disease
What is being tested?
Donepezil and Vitamin E
How many people
Not given
Where
72 sitesin 2 countries
Study dates
Mar 1999to Jan 2004
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 17Show fewer
  • 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.

Who cannot join

  • 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.
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  • 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).
  • 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.

Trial locations and contacts

72 sites in 2 countries.

72 sites in 2 countries

United States63 sites

  • Univ. of New Mexico

    Albuquerque, New Mexico, 89108

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30329

  • Augusta VA Medical Center

    Augusta, Georgia, 30904

  • Johns Hopkins University

    Baltimore, Maryland, 21224

  • Southwestern Vermont Medical Center

    Bennington, Vermont, 05201

  • Baumel-Eisner Neuromedical Institute, Boca Raton

    Boca Raton, Florida, 33486

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Maimonides Medical Center

    Brooklyn, New York, 11219

  • Clinical Neuroscience Research Unit

    Burlington, Vermont, 05401

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush Presbyterian St. Luke's Medical Center

    Chicago, Illinois, 60612

  • University Hospitals of Cleveland

    Cleveland, Ohio, 44120-1013

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • Baumel-Eisner Neuromedical Institute, Ft. Lauderdale

    Fort Lauderdale, Florida, 33321

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202-5111

  • UC Irvine Institute for Brain Aging and Dementia

    Irvine, California, 92697-4285

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32225

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Memory Disorders Institute

    Lakehurst, New Jersey, 08733

  • University of Nevada

    Las Vegas, Nevada, 89102

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky

    Lexington, Kentucky, 40536-0230

  • University of Southern California

    Los Angeles, California, 90033

  • University of California, Los Angeles

    Los Angeles, California, 90095-1769

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • East Bay Institute

    Martinez, California, 94553

  • Wein Center

    Miami Beach, Florida, 33140

  • Baumel-Eisner Neuromedical Institute, MiamiBeach

    Miami Beach, Florida, 33154

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212-8646

  • Yale University

    New Haven, Connecticut, 06520

  • NYU Medical Center

    New York, New York, 10016

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Columbia University

    New York, New York, 11032

  • Medical University of South Carolina

    North Charleston, South Carolina, 29406

  • Nathan S. Kline Institute for Psychiatric Research

    Orangeburg, New York, 10962

  • Brown University

    Pawtucket, Rhode Island, 02860

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • MCP Hahnemann

    Philadelphia, Pennsylvania, 19129

  • Barrow Neurological Group

    Phoenix, Arizona, 85013

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • University of Miami

    Port Charlotte, Florida, 33952

  • Oregon Health Sciences University

    Portland, Oregon, 97201-3098

  • Princeton Biomedical Research, PA

    Princeton, New Jersey, 08540

  • Mayo Clinic

    Rochester, Minnesota, 55901-0144

  • University of Rochester

    Rochester, New York, 14620

  • Sutter Institute for Medical Research

    Sacramento, California, 95816

  • Affiliated Research Instiute

    San Diego, California, 92018

  • University of California, San Diego

    San Diego, California, 92093-0949

  • University of California, San Francisco

    San Francisco, California, 94115

  • University of Washington

    Seattle, Washington, 98108

  • Southern Illinois University

    Springfield, Illinois, 62702

  • Washington University

    St Louis, Missouri, 63110

  • SUNY Stony Brook

    Stony Brook, New York, 11794-8121

  • ClinSearch, Inc.

    Summit, New Jersey, 07901

  • University of South Florida

    Tampa, Florida, 33612

  • Princeton Biomedical - Toms River

    Toms River, New Jersey, 08755

  • University of Arizona

    Tucson, Arizona, 857245023

  • Alzheimer's Research Corp.

    West Long Branch, New Jersey, 07764

  • Premiere Research Institute

    West Palm Beach, Florida, 33407

  • Burke Medical Research Institute

    White Plains, New York, 10605

Other trials in United States

Canada9 sites

  • University of Calgary

    Calgary, Alberta, T2N 4N1

  • Fredericton Medical Clinic

    Fredericton, New Brunswick, E3B 6H5

  • Geriatric Medicine Research Group

    Halifax, Nova Scotia, B3H 2E1

  • St. Joseph's Health Center

    London, Ontario, N6A 4V2

  • Jewish General Hospital Memory Clinic

    Montreal, Quebec, H3T 1E2

  • Elizabeth Bruyere Centre

    Ottawa, Ontario, K1N 5C8

  • Sunnybrook Health Science Center

    Toronto, Ontario, M4N 3M5

  • University of British Columbia

    Vancouver, British Columbia, V6T 2B5

  • McGill Centre for Studies in Aging

    Verdun, Quebec, H4H 1R3

Other trials in Canada

About this 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)

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.

Read the 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.

Being tested
Donepezil, Vitamin E
Keywords
Mild cognitive impairment, Alzheimer's disease, Memory, Donepezil, Vitamin E, Antioxidants, Cholinergic agents, Cholinesterase inhibitors
Medical subject headings
Alzheimer Disease, Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DonepezilDrug

  • Vitamin EDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 1999 (estimated)
  2. Study startMar 1999
  3. Primary completionJan 2004
  4. Study completionJan 2004

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000173
Sponsor's protocol ID
IA0011
Other IDs
3U01AG010483-08S2
Status last verified
Jun 2009
First submitted
29 Oct 1999
Last updated
11 Dec 2009
Results posted
No

Publications

  • 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.

    PubMed 9443470

  • Petersen 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.

    PubMed 9447429

  • Rubin 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.

    PubMed 2650663

  • Grundman 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.

    PubMed 14732621

  • Potashman 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.

    PubMed 36879199

  • Lansdall 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.

    PubMed 36641605

  • Donohue 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.

    PubMed 36627206

  • Oxtoby 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.

    PubMed 35719690

  • DeCarli 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.

    PubMed 17210817

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Donepezil and Vitamin E in people with Alzheimer Disease, run by National Institute on Aging (NIA) at 72 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2009. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 72 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00000173, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2009.

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