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A Randomized, Placebo-Controlled Trial of Latrepirdine in Huntington Disease
Karl Kieburtz, MD, MPH;
Michael P. McDermott, PhD;
Tiffini S. Voss, MD;
Jody Corey-Bloom, MD, PhD;
Lisa M. Deuel, BA;
E. Ray Dorsey, MD, MBA;
Stewart Factor, DO;
Michael D. Geschwind, MD, PhD;
Karen Hodgeman, CCRA;
Elise Kayson, MS, RNC;
Sarah Noonberg, MD, PhD;
Michael Pourfar, MD;
Karen Rabinowitz, JD;
Bernard Ravina, MD, MSCE;
Juan Sanchez-Ramos, MD, PhD;
Lynn Seely, MD;
Francis Walker, MD;
Andrew Feigin, MD; and The Dimebon in Subjects With Huntington Disease (DIMOND) Investigators of the Huntington Study Group
Arch Neurol. 2010;67(2):154-160.
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
Author Affiliations: Departments of Neurology (Dr Kieburtz, McDermott, Voss, Dorsey, and Ravina and Ms Deuel) and Biostatistics and Computational Biology (Dr McDermott) and Clinical Trials Coordination Center (Mss Hodgeman, Kayson, and Rabinowitz), School of Medicine and Dentistry, University of Rochester, Rochester, New York; Department of Neurosciences, University of California, San Diego (Dr Corey-Bloom); Department of Neurology, Emory University, Atlanta, Georgia (Dr Factor); Memory and Aging Center, University of California, San Francisco (Dr Geschwind) and Medivation Inc, San Francisco (Drs Noonberg and Seely); Departments of Neurology, North Shore–Long Island Jewish Health System, Manhasset, New York (Drs Pourfar and Feigin), University of South Florida College of Medicine, Tampa (Dr Sanchez-Ramos), and Wake Forest University School of Medicine, Winston-Salem, North Carolina (Dr Walker). Dr Voss is currently with the Department of Neurology, University of Virginia–Charlottesville.
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