Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2010 Feb;67(2):154-60.
doi: 10.1001/archneurol.2009.334.

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

Karl Kieburtz  1 , 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; Huntington Disease Study Group DIMOND Investigators
Collaborators, Affiliations
Randomized Controlled Trial

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

Karl Kieburtz et al. Arch Neurol. 2010 Feb.

Erratum in

  • Arch Neurol. 2010 Apr;67(4):492. Dimebon in Subjects With Huntington Disease (DIMOND)Investigators of the Huntington Study Group [corrected to Huntington Disease Study Group DIMOND Investigators]

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.

Trial registration: ClinicalTrials.gov NCT00497159.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Participant flow through the study. ECG indicates electrocardiography.
Figure 2
Figure 2
Change over time in Mini-Mental State Examination score by treatment group. The values plotted are adjusted group means derived from a repeated-measures analysis of covariance model. The bars indicate 1 SEM. Positive mean change indicates improvement.
Figure 3
Figure 3
Change over time in Alzheimer Disease Assessment Scale–cognitive subscale score by treatment group. The values plotted are adjusted group means derived from a repeated-measures analysis of covariance model. The bars indicate 1 SEM. Negative mean change indicates improvement.
Figure 4
Figure 4
Change over time in the Unified Huntington's Disease Rating Scale score for behavioral frequency × severity by treatment group. The values plotted are adjusted group means derived from a repeated-measures analysis of covariance model. The bars indicate 1 SEM. Negative mean change indicates improvement.
See this image and copyright information in PMC

References

    1. Panov AV, Burke JR, Strittmatter WJ, Greenamyre JT. In vitro effects of polyglutamine tracts on Ca2+-dependent depolarization of rat and human mitochondria: relevance to Huntington's disease. Arch Biochem Biophys. 2003;410(1):1–6. - PubMed
    1. Tang TS, Slow E, Lupu V, et al. Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease. Proc Natl Acad Sci U S A. 2005;102(7):2602–2607. - PMC - PubMed
    1. Bachurin S, Bukatina E, Lermontova N, et al. Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer. Ann N Y Acad Sci. 2001;939:425–435. - PubMed
    1. Bernales SW, Protter SA, Hung DT. Dimebon incudes neurite outgrowth and mitochondrial stabilization.. Proceedings of the Society for Neuroscience Annual Meeting; Washington, DC. November 15-19, 2008; Washington, DC: Society of Neuroscience; 2008.
    1. Doody RS, Gavrilova SI, Sano M, et al. Dimebon Investigators. Effect of dime-bon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. Lancet. 2008;372(9634):207–215. - PubMed

Publication types

Associated data