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.

Condition	Treatment or Intervention	Phase
Alzheimer Disease	Drug: Rofecoxib  Drug: Naproxen	Phase II Phase III

Further Study Details: 

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.

Ages Eligible for Study:  55 Years and above,  Genders Eligible for Study:  Both

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)

Arizona
      Barrow Neurological Group, Phoenix,  Arizona,  85013,  United States
      University of Arizona, Tucson, Tucson,  Arizona,  85724-5023,  United States
California
      University of California, Davis, Martinez,  California,  94553,  United States
      University of California Irvine Institute for Brain Aging and Dementia, Irvine,  California,  92697-4285,  United States
      University of California, Los Angeles, Los Angeles,  California,  90095-1769,  United States
      University of California, San Diego, La Jolla,  California,  92037,  United States
      University of Southern California, Los Angeles,  California,  90033-1039,  United States
Connecticut
      Yale University, School of Medicine, New Haven,  Connecticut,  06520,  United States
District of Columbia
      Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States
Florida
      Baumel-Eisner Ft Lauderdale, Ft. Lauderdale,  Florida,  33321,  United States
      Baumel-Eisner Neuromedical Institute, Boca Raton, Boca Raton,  Florida,  33486,  United States
      Baumel-Eisner Neuromedical Institute, MiamiBeach, Miami Beach,  Florida,  33154,  United States
      Mayo Clinic Jacksonville, Jacksonville,  Florida,  32225,  United States
      Premiere Research Institute, West Palm Beach,  Florida,  33407,  United States
      University of South Florida, Tampa,  Florida,  33617,  United States
      Wein Center, Miami Beach,  Florida,  33140,  United States
Georgia
      Emory University, Atlanta,  Georgia,  30329,  United States
Illinois
      Rush Presbyterian St. Luke's Medical Center, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana University Medical Center, Indianapolis,  Indiana,  46202-5266,  United States
Kansas
      Kansas University, Kansas City,  Kansas,  66160,  United States
Kentucky
      University of Kentucky, Lexington,  Kentucky,  40536-0230,  United States
Michigan
      University of Michigan, Ann Arbor,  Michigan,  48109,  United States
Minnesota
      University of Minnesota, Minneapolis,  Minnesota,  55455,  United States
Missouri
      Washington University, St. Louis,  Missouri,  63108-2293,  United States
Nevada
      University of Nevada, Las Vegas,  Nevada,  89102,  United States
New Jersey
      ClinSearch, Inc, Summit,  New Jersey,  07901,  United States
New York
      Columbia University, New York,  New York,  10032,  United States
      New York University Medical Center, New York,  New York,  10016,  United States
      University of Rochester Medical Center, Rochester,  New York,  14620,  United States
Ohio
      University Hospitals of Cleveland, Cleveland,  Ohio,  44120,  United States
Oregon
      Oregon Health Sciences University, Portland,  Oregon,  97201-3098,  United States
Pennsylvania
      University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
      University of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Rhode Island
      Memorial Hospital of Rhode Island, Providence,  Rhode Island,  02906,  United States
South Carolina
      Medical University of South Carolina, North Charleston,  South Carolina,  29406,  United States
Tennessee
      Vanderbilt University Medical Center, Nashville,  Tennessee,  37212-8646,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
      University of Texas, SW Medical Center, Dallas,  Texas,  75390-9070,  United States
Vermont
      Southwestern Vermont Medical Center, Bennington,  Vermont,  05201,  United States
Washington
      University of Washington, Seattle,  Washington,  98108,  United States

Study chairs or principal investigators

Leon Thal, MD,  Principal Investigator,  Alzheimer's Disease Cooperative Study   

Study ID Numbers:  IA0021
Record last reviewed:  March 2005
Last Updated:  March 2, 2005
Record first received:  February 28, 2000
ClinicalTrials.gov Identifier:  NCT00004845
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08