Cognition DisordersPhase 4NCT00267163
Brain Imaging and Mental Disorders of Aging Intervention
A Phase 4 study testing donepezil in people with Cognition Disorders, run by National Institute on Aging (NIA) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 to 90 years
- Conditions the study is for
- Cognition Disorders
- What is being tested?
- donepezil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2000to Jul 2007
- Phase
- Phase 4
- 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 40 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA, The Semel Institute for Neuroscience and Human Behavior
Los Angeles, California, 90024
About this study
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.
Read the detailed description
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
- Cognition Disorders
- Being tested
- donepezil, Placebo
- Keywords
- Alzheimer's disease, Mild Cognitive Impairment
- Medical subject headings
- Cognition Disorders, Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
donepezilDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 1. | Experimental | Not described Receives: Drug: donepezil |
| 2. | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in cognition and brain metabolism measured by PET and MRI scans, and neuropsychological testing
Measured: at 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2005 (estimated)
- Study startSep 2000
- Primary completionJul 2007
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cognition DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Investigators
- Gary W. Small, MD, Principal investigator, University of California, Los Angeles, Neuropsychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00267163
- Sponsor's protocol ID
- IA0090
- Other IDs
- 9R01AG018487-06
- Status last verified
- Aug 2008
- First submitted
- 16 Dec 2005
- Last updated
- 29 Aug 2008
- Results posted
- No
Publications
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.
PubMed 10227623Small 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.
PubMed 10401448Ercoli 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.
PubMed 12801154Silverman 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.
PubMed 11694153Small 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.
PubMed 10811879
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Imaging and Mental Disorders of Aging Intervention
- ClinicalTrials.gov ID
- NCT00267163
- Acronym / sponsor ID
- IA0090
- Conditions
- Cognition Disorders
- Keywords
- Alzheimer's disease, Mild Cognitive Impairment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- Sep 2000
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 20 Dec 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1. | Experimental | Drug: donepezil |
| 2. | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 40 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| donepezil | Drug | 1. |
| Placebo | Drug | 2. |
Primary outcome
Changes in cognition and brain metabolism measured by PET and MRI scans, and neuropsychological testing
Time frame: at 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2008.
- Background: PubMed 10227623Small 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.
- Background: PubMed 10401448Small 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.
- Background: PubMed 12801154Ercoli 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.
- Background: PubMed 11694153Silverman 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.
- Background: PubMed 10811879Small 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary W. Small, MD principal investigator
University of California, Los Angeles, Neuropsychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing donepezil in people with Cognition Disorders, run by National Institute on Aging (NIA) at 1 site in United States.
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 10 inclusion and 10 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 29 Aug 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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.
What does the primary outcome measure?
Changes in cognition and brain metabolism measured by PET and MRI scans, and neuropsychological testing (time frame: at 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00267163, which also lists 5 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 29 Aug 2008.