Brain Imaging and Mental Disorders of Aging Intervention

NCT ID: NCT00267163

Last Updated: 2008-08-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-09-30

Study Completion Date

2007-07-31

Brief Summary

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The goal of this project is to determine if a cholinesterase inhibitor is more effective than placebo in delaying cognitive and brain functional decline in people at risk for Alzheimer's disease.

Detailed Description

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Studies to date show that pictures of the brain using PET (positron emission tomography) scan measures predict memory decline in people with genetic risks for developing AD. They have also been shown to predict memory decline in people with mild memory complaints. These findings are consistent with other evidence that the changes of Alzheimer's Disease (AD) begin years before the doctor can confirm a diagnosis.

In this study, PET and genetic risk studies will be performed in people with mild memory complaints. A total of 138 participants (age 40 to 90 years) who are at risk for further memory decline will be enrolled. They will be randomized (like the flip of a coin) to one of two treatment groups, donepezil (a medication to treat mild AD) or placebo, and followed 18 months for evidence of future decline. Participants will receive magnetic resonance imaging (MRI) scans, PET scans, genetic risk assessment for Alzheimer's Disease, and neuropsychological assessments. Repeat brain imaging studies will be performed at the end of the 18-month treatment trial.

These procedures will allow researchers to explore how baseline brain function and genetic risk for AD onset influences brain metabolic rate and memory decline, and treatment outcome. Participants receiving donepezil are expected to show less evidence of decline than those receiving placebo. This project will expand a growing research program in early detection and prevention of AD, designed (1) to identify persons without memory complaints who are most likely to benefit from early intervention and (2) to provide an objective way to monitor the activity in the brain.

Conditions

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Cognition Disorders

Keywords

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Alzheimer's disease Mild Cognitive Impairment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Study Groups

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1.

Group Type EXPERIMENTAL

donepezil

Intervention Type DRUG

2.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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donepezil

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Agreement to participate in a 18 month clinical trial
* NIMH diagnostic criteria for age-associated memory impairment (AAMI)
* Age 40 to 90 years
* MMSE score between 24 and 30 (unless \< 8 years of educational achievement)
* No significant cerebrovascular disease - modified Ischemic Score of \< 4
* The following medications are allowed if stable for \> 1 month: antidepressants (without anticholinergic effects) if not currently depressed and no history of major depression for 2 years; estrogen replacement therapy; thyroid replacement therapy as long as patient is euthyroid
* On entering the study, there must be a family member or potential caregiver available in case the patient develops cognitive impairment that interferes with independent study participation.
* Memory and verbal fluency cut-off scores increasing the probability of incipient dementia (Buschke-Fuld - 34; verbal fluency - 46 for letters, 7 for categories; Benton Visual Retention - 5)
* Adequate visual and auditory acuity to allow neuropsychological testing
* Screening laboratory tests and ECG without significant abnormalities that might interfere with the study

Exclusion Criteria

* Diagnosis of possible or probable AD or any other dementia (e.g., vascular, Lewy body, frontotemporal)
* Evidence of neurologic or other physical illness that could produce cognitive deterioration, including Parkinson's disease; volunteers with a history of TIAs, carotid bruits, or lacunes on MRI scan will be excluded
* History of myocardial infarction within the previous year or unstable cardiac disease
* Uncontrolled hypertension, history of significant liver disease, clinically significant pulmonary disease, diabetes, or cancer
* Such current major psychiatric disorders as mania, according to DSMIV criteria, within the previous two years
* Current diagnosis or history of alcoholism or drug dependence
* Evidence of untreated depression
* Use of any of the following drugs: centrally active beta-blockers, narcotics, clonidine, anti-Parkinsonian medications, antipsychotics, benzodiazepines, systemic corticosteroids, medications with significant cholinergic or anticholinergic effects, anti-convulsants, or warfarin; vitamins other than the standard multivitamin supplement, ginkgo biloba, and any nutraceuticals will not be allowed; once enrolled in the study, occasional chloral hydrate use will be allowed, but discouraged, for insomnia
* Use of any investigational drugs within the previous month or longer, depending on drug half-life
* Contraindication for MRI scan (e.g., metal in body, claustrophobia)
Minimum Eligible Age

40 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role lead

Principal Investigators

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Gary W. Small, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles, Neuropsychiatric Institute

Locations

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UCLA, The Semel Institute for Neuroscience and Human Behavior

Los Angeles, California, United States

Site Status

Countries

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United States

References

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Small SA, Stern Y, Tang M, Mayeux R. Selective decline in memory function among healthy elderly. Neurology. 1999 Apr 22;52(7):1392-6. doi: 10.1212/wnl.52.7.1392.

Reference Type BACKGROUND
PMID: 10227623 (View on PubMed)

Small GW, Chen ST, Komo S, Ercoli L, Bookheimer S, Miller K, Lavretsky H, Saxena S, Kaplan A, Dorsey D, Scott WK, Saunders AM, Haines JL, Roses AD, Pericak-Vance MA. Memory self-appraisal in middle-aged and older adults with the apolipoprotein E-4 allele. Am J Psychiatry. 1999 Jul;156(7):1035-8. doi: 10.1176/ajp.156.7.1035.

Reference Type BACKGROUND
PMID: 10401448 (View on PubMed)

Ercoli LM, Siddarth P, Dunkin JJ, Bramen J, Small GW. MMSE items predict cognitive decline in persons with genetic risk for Alzheimer's disease. J Geriatr Psychiatry Neurol. 2003 Jun;16(2):67-73. doi: 10.1177/0891988703016002001.

Reference Type BACKGROUND
PMID: 12801154 (View on PubMed)

Silverman DH, Small GW, Chang CY, Lu CS, Kung De Aburto MA, Chen W, Czernin J, Rapoport SI, Pietrini P, Alexander GE, Schapiro MB, Jagust WJ, Hoffman JM, Welsh-Bohmer KA, Alavi A, Clark CM, Salmon E, de Leon MJ, Mielke R, Cummings JL, Kowell AP, Gambhir SS, Hoh CK, Phelps ME. Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome. JAMA. 2001 Nov 7;286(17):2120-7. doi: 10.1001/jama.286.17.2120.

Reference Type BACKGROUND
PMID: 11694153 (View on PubMed)

Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6037-42. doi: 10.1073/pnas.090106797.

Reference Type BACKGROUND
PMID: 10811879 (View on PubMed)

Other Identifiers

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9R01AG018487-06

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IA0090

Identifier Type: -

Identifier Source: org_study_id