Anti-Inflammatory Treatment for Age-Associated Memory Impairment: A Double-Blind Placebo-Controlled Trial
| Status: | Completed |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 40 - 90 |
| Updated: | 10/18/2018 |
| Start Date: | June 2000 |
| End Date: | August 2005 |
This project is designed to study whether anti-inflammatory drugs, such as celecoxib, may
delay age-related mental decline. We are also looking at genetic risk and brain structure as
potential predictors of mental decline. We believe people with age-associated memory
impairment who take celecoxib will show less evidence of mental decline than those receiving
placebo (an inactive pill) after 18 months. We expect that brain structure at the start of
the study, memory performance as indicated by tests, and age will be additional predictors of
mental decline. We also predict that cognitive decline (i.e., decline in thinking and memory)
and treatment response will vary according to genetic factors that may correlate with the age
at which dementia begins. We believe other variables such as prior educational achievement,
memory capability at the outset of the study, and gender may influence mental decline and
treatment response. We will study people with age-associated memory impairment (mild memory
complaints, decreased performance in selected memory tests), between 40 and 90 years of age.
The subjects will be randomly (i.e., by a process similar to flipping a coin) assigned to
treatment groups. The subjects will receive either an inactive substance (placebo) or
celecoxib (400 mg/day). The subjects will receive a magnetic resonance imaging (MRI) scan,
FDG PET scan, routine laboratory blood tests, electrocardiogram and cognitive tests. They
will be followed for approximately 18 months and asked to return at specific intervals for
follow-up testing. Measures of brain structure will be derived from baseline MRI scans and
metabolic activity from PET scans, and blood will be drawn and tested to determine which
forms (genotypes) of certain genetically determined cellular components the patient has.
delay age-related mental decline. We are also looking at genetic risk and brain structure as
potential predictors of mental decline. We believe people with age-associated memory
impairment who take celecoxib will show less evidence of mental decline than those receiving
placebo (an inactive pill) after 18 months. We expect that brain structure at the start of
the study, memory performance as indicated by tests, and age will be additional predictors of
mental decline. We also predict that cognitive decline (i.e., decline in thinking and memory)
and treatment response will vary according to genetic factors that may correlate with the age
at which dementia begins. We believe other variables such as prior educational achievement,
memory capability at the outset of the study, and gender may influence mental decline and
treatment response. We will study people with age-associated memory impairment (mild memory
complaints, decreased performance in selected memory tests), between 40 and 90 years of age.
The subjects will be randomly (i.e., by a process similar to flipping a coin) assigned to
treatment groups. The subjects will receive either an inactive substance (placebo) or
celecoxib (400 mg/day). The subjects will receive a magnetic resonance imaging (MRI) scan,
FDG PET scan, routine laboratory blood tests, electrocardiogram and cognitive tests. They
will be followed for approximately 18 months and asked to return at specific intervals for
follow-up testing. Measures of brain structure will be derived from baseline MRI scans and
metabolic activity from PET scans, and blood will be drawn and tested to determine which
forms (genotypes) of certain genetically determined cellular components the patient has.
Several observational epidemiological studies indicate that anti-inflammatory treatments
attenuate or prevent the symptoms of one of the most common mental disorders of late life,
Alzheimer's disease (AD). Neuropathological studies also support inflammatory or immune
mechanisms in AD, including findings of reactive microglia within or near AD lesions. Such
evidence, however, is circumstantial, and controlled, randomized drug trials are needed to
determine efficacy.
This project is designed to determine if the commonly used nonsteroidal anti-inflammatory
drug (NSAID), celecoxib, is efficacious in delaying progression of cognitive symptoms in
people with age-related cognitive losses who are at risk for developing AD. A total of 135
subjects with age-associated memory impairment (AAMI) who are at risk for further cognitive
decline (age 40 to 90 years) will be randomized (double-blind design) to one of two treatment
groups: celecoxib (400 mg/d) or placebo, and followed for 18 months. All randomized subjects
will receive magnetic resonance imaging (MRI) scans, FDG PET scans, and selective genotyping
(apolipoprotein E [APOE] and genetic risk for AD onset (e.g., APOE-4). Subjects receiving
celecoxib are expected to show less evidence of cognitive decline than those receiving
placebo. The proposed project builds upon our group's prior work on early detection of AD
using brain imaging, genetic risk, and neuropsychological assessments. This project also is a
logical follow-up to recent observational studies of a promising early intervention and will
represent one of the first controlled, anti-inflammatory treatment trials for persons at high
risk for age-related cognitive decline and the eventual development of AD.
Subjects will be followed closely to ensure that medication is safely used, without side
effects (e.g., gastrointestinal, renal, etc.).
attenuate or prevent the symptoms of one of the most common mental disorders of late life,
Alzheimer's disease (AD). Neuropathological studies also support inflammatory or immune
mechanisms in AD, including findings of reactive microglia within or near AD lesions. Such
evidence, however, is circumstantial, and controlled, randomized drug trials are needed to
determine efficacy.
This project is designed to determine if the commonly used nonsteroidal anti-inflammatory
drug (NSAID), celecoxib, is efficacious in delaying progression of cognitive symptoms in
people with age-related cognitive losses who are at risk for developing AD. A total of 135
subjects with age-associated memory impairment (AAMI) who are at risk for further cognitive
decline (age 40 to 90 years) will be randomized (double-blind design) to one of two treatment
groups: celecoxib (400 mg/d) or placebo, and followed for 18 months. All randomized subjects
will receive magnetic resonance imaging (MRI) scans, FDG PET scans, and selective genotyping
(apolipoprotein E [APOE] and genetic risk for AD onset (e.g., APOE-4). Subjects receiving
celecoxib are expected to show less evidence of cognitive decline than those receiving
placebo. The proposed project builds upon our group's prior work on early detection of AD
using brain imaging, genetic risk, and neuropsychological assessments. This project also is a
logical follow-up to recent observational studies of a promising early intervention and will
represent one of the first controlled, anti-inflammatory treatment trials for persons at high
risk for age-related cognitive decline and the eventual development of AD.
Subjects will be followed closely to ensure that medication is safely used, without side
effects (e.g., gastrointestinal, renal, etc.).
Inclusion Criteria:
- Age-associated memory impairment (AAMI)
Exclusion Criteria:
- Use of cholinesterase inhibitors
- Any current major psychiatric disorder such as depression or mania
- Subjects who may be sensitive to potential side effects of celecoxib, including those
with any evidence of renal disease or gastrointestinal disease or predisposition or
risk for bleeding, particularly gastrointestinal
- Subjects with histories of congestive heart failure, hypertension, peptic ulcer
disease, any bleeding disorder, or other medical conditions that might increase
medical risks from NSAID sensitivity
- Current diagnosis or history of alcoholism or drug dependence
- Evidence of depression
- Subjects with a contraindication for MRI scan
- Sulfur allergy
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