A randomized, placebo-controlled trial of latrepirdine in Huntington disease
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, Huntington Disease Study Group DIMOND Investigators, Karl Kieburtz, Andrew Feigin, Merit Cudkowicz, Karen Hodgeman, Elise Kayson, Michael P McDermott, Karen Rabinowitz, Bernard Ravina, Lynn Seely, Wendy Seitz, Tiffini S Voss, Francis Walker, Jody Corey-Bloom, Stephanie Lessig, Jody Goldstein, Francis Walker, Michael S Cartwright, Vicki Hunt, Christine O'Neill, E Ray Dorsey, Charlyne Hickey, Lisa M Deuel, Steven Hersch, Alex Bender, Joanne Wojcieszek, Joanne Belden, Steven Frucht, Carol Moskowitz, Stewart Factor, Joan Harrison, Cathleen Wood-Siverio, Michael Pourfar, Jean Ayan, Michael D Geschwind, Mira Guzijan, Erika Mozer, Juan Sanchez-Ramos, Marcia McCall, Kolleen Elliott, Adam Rosenblatt, Abhijit Agarwal, Claire Welsh, Nadine Yoritomo, Vicki Wheelock, Teresa Tempkin, Sandra Kostyk, Allison Seward, Eric Molho, Sharon Evans, Constance Nickerson, Amy Colcher, Lisa Altin, Mary Matthews, Kathleen Shannon, Jeana Jaglin, Roger A Barker, Benjamin Wright, Sarah Mason, Connie Orme, Joseph Weber, Arthur Watts, Michele Bronson, David Hung, Alexander McNees, Brian Selby, Michelle Stanley, Rob Tatum, Monica Sweany, Carl Leventhal, Roger Porter, Jason Roy, 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, Huntington Disease Study Group DIMOND Investigators, Karl Kieburtz, Andrew Feigin, Merit Cudkowicz, Karen Hodgeman, Elise Kayson, Michael P McDermott, Karen Rabinowitz, Bernard Ravina, Lynn Seely, Wendy Seitz, Tiffini S Voss, Francis Walker, Jody Corey-Bloom, Stephanie Lessig, Jody Goldstein, Francis Walker, Michael S Cartwright, Vicki Hunt, Christine O'Neill, E Ray Dorsey, Charlyne Hickey, Lisa M Deuel, Steven Hersch, Alex Bender, Joanne Wojcieszek, Joanne Belden, Steven Frucht, Carol Moskowitz, Stewart Factor, Joan Harrison, Cathleen Wood-Siverio, Michael Pourfar, Jean Ayan, Michael D Geschwind, Mira Guzijan, Erika Mozer, Juan Sanchez-Ramos, Marcia McCall, Kolleen Elliott, Adam Rosenblatt, Abhijit Agarwal, Claire Welsh, Nadine Yoritomo, Vicki Wheelock, Teresa Tempkin, Sandra Kostyk, Allison Seward, Eric Molho, Sharon Evans, Constance Nickerson, Amy Colcher, Lisa Altin, Mary Matthews, Kathleen Shannon, Jeana Jaglin, Roger A Barker, Benjamin Wright, Sarah Mason, Connie Orme, Joseph Weber, Arthur Watts, Michele Bronson, David Hung, Alexander McNees, Brian Selby, Michelle Stanley, Rob Tatum, Monica Sweany, Carl Leventhal, Roger Porter, Jason Roy
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.
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Source: PubMed