A randomized, placebo-controlled trial of latrepirdine in Huntington disease.

Abstract

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.

• Authors: Karl Kieburtz, Michael P McDermott, Tiffini S Voss, Jody Corey-Bloom, Lisa M Deuel, E Ray Dorsey, Stewart Factor, Michael D Geschwind, Karen Hodgeman, Elise Kayson, Sarah Noonberg, Michael Pourfar, Karen Rabinowitz, Bernard Ravina, Juan Sanchez-Ramos, Lynn Seely, Francis Walker, Andrew Feigin, Dimebon in Subjects with Huntington Disease (DIMOND) Investigators of the Huntington Study Group, Huntington Disease Study Group DIMOND Investigators
• Journal: Archives of neurology (Arch Neurol) Vol. 67 Issue 2 Pg. 154-60 (Feb 2010) ISSN: 1538-3687 [Electronic] United States
• PMID: 20142523 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Indoles
• latrepirdine

Topics

• Adult
• Aged
• Antipsychotic Agents (therapeutic use)
• Cognition (drug effects)
• Double-Blind Method
• Electrocardiography (methods)
• Female
• Humans
• Huntington Disease (drug therapy, physiopathology)
• Indoles (therapeutic use)
• Male
• Mental Status Schedule
• Middle Aged
• Motor Activity (drug effects)
• Neuropsychological Tests
• Retrospective Studies
• Time Factors
• Treatment Outcome