Objectives  To evaluate the safety and tolerability of latrepirdine in Huntington disease (HD) and explore its effects on cognition, behavior, and motor symptoms.

Design  Double-blind, randomized, placebo-controlled trial.

Setting  Multicenter outpatient trial.

Participants  Ninety-one participants with mild to moderate HD enrolled at 17 US and UK centers from July 18, 2007, through July 16, 2008.

Intervention  Latrepirdine, 20 mg 3 times daily (n = 46), or matching placebo (n = 45) for a 90-day treatment period.

Main Outcome Measures  The primary outcome variable was tolerability, defined as the ability to complete the study at the assigned drug dosage. Secondary outcome variables included score changes from baseline to day 90 on the Unified Huntington's Disease Rating Scale (UHDRS), the Mini-Mental State Examination (MMSE), and the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog).

Results  Latrepirdine was well tolerated (87% of the patients given latrepirdine completed the study vs 82% in the placebo group), and adverse event rates were comparable in the 2 groups (70% in the latrepirdine group and 80% in the placebo group). Treatment with latrepirdine resulted in improved mean MMSE scores compared with stable performance in the placebo group (treatment effect, 0.97 points; 95% confidence interval, 0.10-1.85; P = .03). No significant treatment effects were seen on the UHDRS or the ADAS-cog.

Conclusions  Short-term administration of latrepirdine is well tolerated in patients with HD and may have a beneficial effect on cognition. Further investigation of latrepirdine is warranted in this population with HD.

Trial Registration  clinicaltrials.gov Identifier: NCT00497159