Evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer's disease suggests that anti-inflammatory medications may slow the rate of cognitive deterioration. We have selected two anti- inflammatory drugs for a therapeutic trial: hydroxychloroquine, an antimalarial agent with anti-inflammatory and immunomodulating effects useful in the treatment of rheumatic disease, and colchicine, an anti- inflammatory drug with anti-amyloidogenic activity. The trial employs a double-blind parallel design with three groups: hydroxychloroquine (200mg twice daily), colchicine (0.6mg twice daily) and placebo. A total of three hundred subjects will be randomized to the three groups. The duration of treatment will be one year, with monitoring for an additional three months. The primary outcome measure will be the one year change in the cognitive subscale of the Alzheimer's Disease Assessment Scale. Secondary outcome measures include the Clinical Dementia Rating Scale sum of boxes (CDR-SOB), the attainment of significant endpoints (death, institutionalization, 1 point worsening on the global CDR, 15 point decline on the ADCS activities of daily living (ADL) inventory), the CERAD Behavioral Rating Scale, and the ADCS global, quality of life and pharmacoeconomic scales.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project--Cooperative Agreements (U01)
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University of California San Diego
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