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 clinicaltrials.gov Identifier: NCT00920946.