A Randomized, Placebo-Controlled Trial of Latrepirdine in Huntington Disease

• Published in: Archives of neurology (Chicago) Vol. 67; no. 2; pp. 154 - 160
• Main Authors: Kieburtz, Karl, McDermott, Michael P, Voss, Tiffini S, Corey-Bloom, Jody, Deuel, Lisa M, Dorsey, E. Ray, Factor, Stewart, Geschwind, Michael D, Hodgeman, Karen, Kayson, Elise, Noonberg, Sarah, Pourfar, Michael, Rabinowitz, Karen, Ravina, Bernard, Sanchez-Ramos, Juan, Seely, Lynn, Walker, Francis, Feigin, Andrew
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.02.2010
• Subjects: Adult; Aged; Antipsychotic Agents - therapeutic use; Biological and medical sciences; Cognition & reasoning; Cognition - drug effects; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Double-Blind Method; Drugs; Electrocardiography - methods; Female; Humans; Huntington Disease - drug therapy; Huntington Disease - physiopathology; Huntingtons disease; Indoles - therapeutic use; Male; Medical research; Medical sciences; Mental Status Schedule; Middle Aged; Motor Activity - drug effects; Neurology; Neuropsychological Tests; Pharmacology; Retrospective Studies; Time Factors; Treatment Outcome; United Kingdom > UK; United States > US; Nervous system diseases; Central nervous system disease; Huntington disease; Placebo; Degenerative disease; Genetic disease; Cerebral disorder; Extrapyramidal syndrome
• ISSN: 0003-9942; 2168-6149; 1538-3687; 1538-3687; 2168-6157
• DOI: 10.1001/archneurol.2009.334

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: NCT00497159Arch Neurol. 2010;67(2):154-160-->