Clinical trial NCT00004845: A Multicenter Trial of Rofecoxib and Naproxen in Alzheimer's Disease (NSAID Study)
Official title: A Multicenter Trial of Rofecoxib and Naproxen in Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alzheimer Disease
Keywords: Anti-inflammatory
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
Collaborators: name: Alzheimer's Disease Cooperative Study (ADCS)
First posted: 2000-02-29
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: The primary specific aim of this clinical trial is to determine whether treatment with rofecoxib or naproxen for one year will slow the rate of decline of cognitive function in patients with Alzheimer's disease (AD) as measured by ADAScog.

Detailed description: Evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer's disease along with a number of epidemiological studies suggests that non-steroidal anti-inflammatory drugs (NSAIDs) may slow the rate of cognitive deterioration. We have selected two such drugs for a therapeutic trial: rofecoxib and naproxen. The trial employs a double-blind parallel design with three primary treatment groups: rofecoxib, naproxen and placebo. A total of 320 patients will be enrolled in the trial and randomized to the three groups. Stable use of cholinesterase inhibitors, estrogen, low dose aspirin, and vitamin E will be allowed. Patients with inflammatory diseases that might respond to the study medications will be excluded.

The primary outcome measure will be the one year change in the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAScog). The attainment of significant endpoints will be examined as a secondary outcome measure. Other secondary measures include the CDR sum-of-boxes, Neuropsychiatric Inventory, the Quality of Life-AD and the ADCS pharmacoeconomic scale. The influence of HLA-DR (Human Leukocyte Antigen) genotype on clinical progression and response to treatment will also be examined.

Eligibility criteria: Inclusion Criteria:

* NINCDS/ADRDA criteria for probable AD
* MMSE between 13 and 26, inclusive
* Stable medical condition for 3 months
* Screening visit
* Physically acceptable for this study as confirmed by medical history, physical exam, neurologic exam, and clinical laboratory tests
* Supervision available for administration of study medications; caregiver/informant to accompany patient to all scheduled visits
* Fluent in English or Spanish
* Age greater than or equal to 55 years old
* Modified Hachinski of less than or equal to 4
* CT or MRI since onset of memory impairment demonstrating absence of clinically significant focal lesion
* Able to complete baseline assessments
* 6 years of education or work history sufficient to exclude mental retardation
* Able to ingest oral medication

Exclusion Criteria:

* Hypersensitivity to aspirin or NSAID
* Active peptic ulcer disease within 5 years
* Renal insufficiency with creatinine greater than 1.5
* Clinically significant liver disease
* Poorly controlled hypertension
* Congestive heart failure
* Bleeding ulcer
* Active neoplastic disease (skin tumors other than melanoma are not exclusionary; patients with stable prostate cancer may be included at the discretion of the project director)
* Inflammatory diseases (including crystal arthropathy, rheumatoid arthritis, systemic lupus, erythematosus, Sjogren's syndrome, inflammatory bowel disease)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Group
state: Arizona
city: Tucson
country: United States
facility: University of Arizona, Tucson
state: Arizona
city: Irvine
country: United States
facility: University of California Irvine Institute for Brain Aging and Dementia
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Martinez
country: United States
facility: University of California, Davis
state: California
city: New Haven
country: United States
facility: Yale University, School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Boca Raton
country: United States
facility: Baumel-Eisner Neuromedical Institute, Boca Raton
state: Florida
city: Ft Lauderdale
country: United States
facility: Baumel-Eisner Ft Lauderdale
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami Beach
country: United States
facility: Wein Center
state: Florida
city: Miami Beach
country: United States
facility: Baumel-Eisner Neuromedical Institute, MiamiBeach
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush Presbyterian St. Luke's Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Kansas City
country: United States
facility: Kansas University
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Las Vegas
country: United States
facility: University of Nevada
state: Nevada
city: Summit
country: United States
facility: ClinSearch, Inc
state: New Jersey
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Memorial Hospital of Rhode Island
state: Rhode Island
city: North Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas, SW Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Bennington
country: United States
facility: Southwestern Vermont Medical Center
state: Vermont
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Alzheimer's Disease Cooperative Study
name: Leon Thal, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ; Alzheimer's Disease Cooperative Study. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003 Jun 4;289(21):2819-26. doi: 10.1001/jama.289.21.2819.