Memory Impairment Study (Mild Cognitive Impairment Study)

• Status: Completed
• Trial end date: 2004-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute on Aging (NIA)
• Collaborator: Alzheimer's Disease Cooperative Study (ADCS)
• Treatments: alpha-Tocopherol; Donepezil; Tocopherols; Tocotrienols; Vitamin E; Vitamins

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.