A Randomized, Double-blind, Placebo-Controlled Study of Latrepirdine in Patients With Mild to Moderate Huntington Disease

被引：31

作者：

Kieburtz, Karl

Landwehrmeyer, Georg B.

Cudkowicz, Merit

Dorsey, E. Ray

Feigin, Andrew

Hunt, Victoria

Kayson, Elise

McDermott, Michael

Noonberg, Sarah

Seitz, Wendy

Soliveri, Paola ^{[11
]}

Walker, Francis ^{[63
]}

Burgunder, Jean-Marc

Romero, Irene

Magara, Anouk

Stebler, Yanik

Rickards, Hugh ^{[1
,2
]}

Wright, Jan ^{[1
,2
]}

De Souza, Jenny ^{[1
,2
]}

Barker, Roger A. ^{[3
]}

Mason, Sarah ^{[3
]}

Di Pietro, Anna ^{[3
]}

Goodman, Anna ^{[3
]}

O'Keeffe, Deidre ^{[3
]}

Langlois, Melanie ^{[4
]}

Ferland, Germain ^{[4
]}

Verret, Louis ^{[4
]}

Chouinard, Sylvain ^{[5
]}

Paris, Suzanne ^{[5
]}

LePage, Christiane ^{[5
]}

Nemeth, Andrea H. ^{[6
]}

Merritt, Claire ^{[6
]}

Cox, Caroline ^{[6
]}

Astbury, Therese ^{[6
]}

Murphy, Sarah ^{[6
]}

Ahmed, Anwar ^{[7
]}

St Marie, Patricia ^{[7
]}

Berila, Rose Anne ^{[7
]}

Kubu, Cynthia ^{[7
]}

Segro, Vicki ^{[8
]}

Kumar, Rajeev ^{[8
]}

Erickson, Diane ^{[8
]}

Schneiders, Jay ^{[8
]}

Frucht, Steven ^{[9
]}

Wasserman, Paula ^{[9
]}

Moskowitz, Carol ^{[9
]}

Scott, Burton ^{[10
]}

Perry-Trice, Peggy ^{[10
]}

Wyne, Sarah ^{[10
]}

Soliveri, Paola ^{[11
]}

机构：

[1] Birmingham & Solihull Mental Hlth Fdn, Birmingham, W Midlands, England

[2] Birmingham & Solihull Mental Hlth Fdn, Solihull, W Midlands, England

[3] Cambridge Ctr Brain Repair, Cambridge, England

[4] CHU Quebec, Hop Enfants Jesus, Quebec City, PQ, Canada

[5] CHUM Hosp Notre Dame, Montreal, PQ, Canada

[6] Oxford Univ Hosp NHS Trust, Churchill Hosp, Oxford, England

[7] Cleveland Clin, Cleveland, OH 44106 USA

[8] Colorado Neurol Inst, Englewood, CO USA

[9] Columbia Univ, Med Ctr, New York, NY USA

[10] Duke Univ, Durham, NC USA

[11] Fdn IRCCS Ist Neurol C Besta, Milan, Italy

[12] Gabinet Zabiegowy Gdansk, Gdansk, Poland

[13] Guys Hosp, London SE1 9RT, England

[14] Univ Hamburg Hosp, Hamburg, Germany

[15] Hereditary Neurol Dis Ctr, Wichita, KS USA

[16] Idaho Elks Rehabil Ctr, Boise, ID USA

[17] Indiana Univ Sch Med, Indianapolis, IN USA

[18] IRCCS Neuromed Unita Neurogenet, Pozzilli, Italy

[19] Johns Hopkins Univ, Baltimore, MD USA

[20] Karolinska Hosp, S-10401 Stockholm, Sweden

[21] Klin Taufkirchin, Munich, Germany

[22] Krakow Inst, Krakow, Poland

[23] Leiden Univ, Med Ctr, Leiden, Netherlands

[24] London Hlth Sci Ctr, London, England

[25] Massachusetts Gen Hosp, Boston, MA 02114 USA

[26] Med Coll Wisconsin, Milwaukee, WI 53226 USA

[27] Medivat, San Francisco, CA USA

[28] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England

[29] Disorders Res, Subiaco, WA, Australia

[30] Neurogenet Clin, Copenhagen, Denmark

[31] Ohio State Univ, Columbus, OH 43210 USA

[32] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[33] Ruhruniv Bochum, Copenhagen Univ Hosp, Memory Disorders Res Unit, Copenhagen, Denmark

[34] Sheffield Childrens Hosp, Sheffield, S Yorkshire, England

[35] Southampton Gen Hosp, Southampton, Hants, England

[36] Struthers Parkinsons Ctr, Golden Valley, MN USA

[37] St Vincents Aged Psychiat Serv, Melbourne, Vic, Australia

[38] Univ Bari, Bari, Italy

[39] Univ Naples Federico II, Naples, Italy

[40] Univ Klinikum Carl Gustav Carus, Dresden, Germany

[41] Univ Klinikum Charite, Berlin, Germany

[42] Univ Aachen, Aachen, Germany

[43] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada

[44] Univ Calif Davis, Davis Med Ctr, Davis, CA USA

[45] Univ Calif Irvine, Irvine, CA USA

[46] Univ Calif Los Angeles, Los Angeles, CA USA

[47] Univ Calif San Diego, San Diego, CA 92103 USA

[48] Univ Calif San Francisco, San Francisco, CA 94143 USA

[49] Univ Florida, Gainesville, FL USA

[50] Univ Iowa, Iowa City, IA USA

来源：

JAMA NEUROLOGY | 2013年 / 70卷 / 01期

基金：

美国国家卫生研究院;

关键词：

MINI-MENTAL-STATE; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; CONTROLLED-TRIAL; DEMENTIA; DONEPEZIL; DIMEBON; RIVASTIGMINE; DYSFUNCTION; INVENTORY;

D O I：

10.1001/2013.jamaneurol.382

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. Objective: To determine the effect of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. Design: Randomized, double-blind, placebo-controlled study. Setting: Sixty-four research centers in Australia, Europe, and North America. Patients: Four hundred three patients with mild to moderate Huntington disease and baseline cognitive impairment (Mini-Mental State Examination score, 10-26). Intervention: Latrepirdine (20 mg) vs matching placebo administered orally 3 times daily for 26 weeks. Main Outcome Measures: The co-primary outcome measures were cognition as measured by the change in Mini-Mental State Examination score from baseline to week 26 and global function at week 26 as measured by the Clinician Interview-Based Impression of Change, plus carer interview, which ranges from 1 (marked improvement) to 7 (marked worsening). Secondary efficacy outcome measures included behavior, daily function, motor function, and safety. Results: The mean change in Mini-Mental State Examination score among participants randomized to latrepirdine (1.5-point improvement) did not differ significantly from that among participants randomized to placebo (1.3-point improvement) (P=.39). Similarly, the distribution of the Clinician Interview-Based Impression of Change, plus carer interview did not differ significantly among those randomized to latrepirdine compared with placebo (P=.84). No significant treatment effects were detected on the secondary efficacy outcome measures. The incidence of adverse events was similar between those randomized to latrepirdine (68.5%) and placebo (68.0%). Conclusion: In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo. Trial Registration: clinicaltrials.gov Identifier: NCT00920946 JAMA Neurol. 2013;70(1):25-33. Published online October 29, 2012. doi:10.1001/2013.jamaneurol.382

引用

页码：25 / 33

页数：9

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