A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer%26apos;s disease: the DARAD trial

作者：Molloy D William^*; Standish T I; Zhou Q; Guyatt G

来源：International Journal of Geriatric Psychiatry, 2013, 28(5): 463-470.

DOI：10.1002/gps.3846

• Alzheimer%26apos
• s disease
• doxycycline
• rifampin
• randomized
• trial

Objectives Preliminary evidence suggested that doxycycline and rifampin might stop or slow the progression of Alzheimer%26apos;s disease (AD). We carried out a randomized trial to confirm or refute these findings. Methods A multicenter, blinded, randomized, 2x2 factorial controlled trial, set at 14 geriatric outpatient clinics in Canada. Four hundred and six patients with mild to moderate AD (standardized mini mental state examination (SMMSE) score 1426) participated. The intervention was 12months%26apos; treatment with doxycycline 100mg twice daily+rifampin 300mg daily or doxycycline 100mg twice daily+placebo-rifampin daily or rifampin 300mg daily+placebo-doxycycline twice daily or placebo-doxycycline twice daily+placebo-rifampin daily. Coprimary outcomes were the Standardized Alzheimer%26apos;s Disease Assessment Scale-Cognitive Subscale (SADAS-cog) and the Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB). Secondary outcomes were the SMMSE, Quick mild cognitive impairment screen, Geriatric Depression Scale, Cornell Scale for Depression in Dementia, activities of daily living (Lawton Scale), and the Dysfunctional Behavior Rating Instrument frequency and reaction subscales. Results There was a significant deterioration in SADAS-cog over time with both rifampin and doxycycline in comparison with placebo. When the two were used together, there was no statistically significant decline/deterioration in comparison with placebo (n=305). For the CDR-SB, there were no significant effects of either rifampin or doxycycline. Secondary outcome results followed similar patterns. Conclusion Twelve months%26apos; treatment with doxycycline or rifampin, alone or in combination, has no beneficial effects on cognition or function in AD.

• 出版日期2013-5