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Background: Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. Objective: To determine the effect of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. Design: Randomized, double-blind, placebo-controlled study. Setting: Sixty-four research centers in Australia, Europe, and North America. Patients: Four hundred three patients with mild to moderate Huntington disease and baseline cognitive impairment (Mini-Mental State Examination score, 10-26). Intervention: Latrepirdine (20 mg) vs matching placebo administered orally 3 times daily for 26 weeks. Main Outcome Measures: The co-primary outcome measures were cognition as measured by the change in Mini-Mental State Examination score from baseline to week 26 and global function at week 26 as measured by the Clinician Interview-Based Impression of Change, plus carer interview, which ranges from 1 (marked improvement) to 7 (marked worsening). Secondary efficacy outcome measures included behavior, daily function, motor function, and safety. Results: The mean change in Mini-Mental State Examination score among participants randomized to latrepirdine (1.5-point improvement) did not differ significantly from that among participants randomized to placebo (1.3-point improvement) (P=.39). Similarly, the distribution of the Clinician Interview-Based Impression of Change, plus carer interview did not differ significantly among those randomized to latrepirdine compared with placebo (P=.84). No significant treatment effects were detected on the secondary efficacy outcome measures. The incidence of adverse events was similar between those randomized to latrepirdine (68.5%) and placebo (68.0%). Conclusion: In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo. Trial Registration: Identifier: NCT00920946 JAMA Neurol. 2013;70(1):25-33. Published online October 29, 2012. doi:10.1001/2013.jamaneurol.382

Original publication




Journal article


Jama Neurology

Publication Date





25 - 33


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