Accepted for Publication: June 29, 2012.
Published Online: October 29, 2012. doi:10.1001/2013.jamaneurol.382
Author Contributions: Drs Kieburtz, Landwehrmeyer, and McDermott had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Cudkowicz, Dorsey, Feigin, Hunt, Kayson, Kieburtz, Landwehrmeyer, McDermott, Noonberg, Seitz, Soliveri, and Walker. Acquisition of data: Albin, Blindauer, Chiu, Colcher, Corey-Bloom, Craufurd, Cudkowicz, De Michele, de Tommaso, Di Maio, DiPietro, Dorsey, Epping, Feigin, Fischer, Geschwind, Goldstein, Hauser, Hermanowicz, Hjermind, Holt, Ivanco, Jakobsen, Jenkins, Klingelhöfer, Kostyk, Kubu, Leavitt, Loy, Mahant, Marcinkowski, Margolis, McCusker, McDermott, Münchau, Nance, J. E. Nielsen, Niswonger, Noonberg, Novak, Nowak, Orme, Panegyres, Peavy, Priller, Raymond, Reilmann, Rickards, Romrell, Rudzińska, Sacca, Saft, Salvatore, Sass, Seeberger, Seitz, Serpino, Siderowf, Singer, Smith, Squitieri, Storch, Tabrizi, Tempkin, Uhl, Walker, Werner, Wolz, Zielonka, and Zittel. Analysis and interpretation of data: Cudkowicz, Dorsey, Feigin, Fisher, Hunt, Kayson, Kieburtz, Landwehrmeyer, McDermott, Nichols, Noonberg, Orme, Seitz, Soliveri, Walker, Watts, Weber, and White. Drafting of the manuscript: Dorsey. Critical revision of the manuscript for important intellectual content: Albin, Blindauer, Colcher, Corey-Bloom, Craufurd, Cudkowicz, De Michele, de Tommaso, Di Maio, DiPietro, Dorsey, Epping, Feigin, Fischer, Geschwind, Goldstein, Hauser, Hermanowicz, Hjermind, Holt, Ivanco, Jakobsen, Jenkins, Kieburtz, Klingelhöfer, Kostyk, Kubu, Landwehrmeyer, Leavitt, Loy, Mahant, Marcin-kowski, Margolis, McCusker, McDermott, Münchau, Nance, Nichols, J. E. Nielsen, Niswonger, Noonberg, Novak, Nowak, Orme, Panegyres, Peavy, Priller, Raymond, Reilmann, Rickards, Romrell, Rudzińska, Sacca, Saft, Salvatore, Sass, Seeberger, Seitz, Serpino, Siderowf, Singer, Smith, Squitieri, Storch, Tabrizi, Tempkin, Uhl, Walker, Werner, Wolz, Zielonka, and Zittel. Statistical analysis: McDermott and Watts. Obtained funding: Kieburtz. Administrative, technical, and material support: Kayson, Kieburtz, Landwehrmeyer, McNees, and Noonberg. Study supervision: Cudkowicz, Dorsey, Feigin, Hunt, Kayson, Kieburtz, Landwehrmeyer, McDermott, Noonberg, Seitz, Soliveri, and Walker.
Conflict of Interest Disclosures: Dr Corey-Bloom is a principal investigator on multiple clinical trials for the treatment of cognitive dysfunction and dementia sponsored by pharmaceutical companies such as Elan, Medivation, SIENA, and Teva, in addition to the Huntington Study Group, CHDI Foundation, and Alzheimer's Disease Cooperative Study Group. Dr Hauser has received honoraria or payments for consulting, advisory services, speaking services, or research over the past 12 months for the following: advisory boards (Boehringer Ingelheim Pharmaceuticals, Inc, Teva Neuroscience, Impax Pharmaceuticals, UCB, Inc, GE Healthcare, IPSEN Pharmaceuticals, Novartis, Parkinson Study Group, Solvay, Quintiles, and Biogen Idec), speakers' bureau (Allergan Neuroscience, GlaxoSmithKline, Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals, Inc, Novartis Pharmaceuticals, and IPSEN Pharmaceuticals), consulting (Bial, Lundbeck, Biogen Idec, Boehringer Ingelheim, Chelsea Therapeutics, GE Healthcare, Impax, Santhera Pharmaceuticals, Merck Serono/EMD Serono, Solvay Pharmaceuticals, Synosis Therapeutics, Schering-Plough, Shire Pharmaceuticals, Inc, XenoPort, Inc, Medivation, Addex, Adamas Pharmaceuticals, and Noven Pharmaceuticals), research (PICO-Tesla, Schwartz Pharma, Genzyme, Acadia, Solvay Pharmaceuticals, Impax, Teva Neuroscience, [Merck] Serono, Schering-Plough, Novartis Pharmaceuticals, IPSEN Pharmaceuticals, XenoPort Pharmaceuticals, Chelsea Therapeutics, Allergan Neuroscience, Molecular Biometrics, The Michael J. Fox Foundation for Parkinson's Research, and the National Parkinson Foundation), and royalties (University of South Florida). In addition, Dr Hauser has consulted in litigation with lawyers representing various current and former manufacturers of welding consumables. Dr Hermanowicz reports research, clinical trial, speaking honoraria, and salary support from the California Institute for Regenerative Medicine, Huntington Study Group, Lundbeck, and University of California, Irvine. Dr Kieburtz reports serving as a consultant to the National Institutes of Health (National Institute of Neurological Disorders and Stroke), US Food and Drug Administration, US Veterans Administration, Abbott, Acorda, Aptiv, Biogen Idec, Biotie, Biovail, Boehringer Ingelheim, Ceregene, Civitas, Clintrex, Cynapsus, EMD Merck Serono, Genzyme, Impax, Intec, Ipsen, Isis, Knopp, Eli Lilly, Link Medicine, Lundbeck, LZ Therapeutics, Merz, Novartis, Orion, Otsuka, Pharm2B, Phytopharm, Schering-Plough, Siena Biotech, Synosia, Solvay, Synagile, Teva, UCB Pharma, Vaccinex, Vectura, and XenoPort; he also reports grants and research support from Medivation, The Michael J. Fox Foundation, the National Institutes of Health (National Eye Institute, National Institute of Neurological Disorders and Stroke, National Institute on Aging, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development), NeuroSearch, and Pfizer, as well as legal consulting for Pfizer, Thompson Hine, and welding rod litigation defendants. Dr Landwehrmeyer reports receiving consultancy fees from Siena Biotech, AOP Orphan, Teva, and GlaxoSmithKline, as well as grants for Huntington disease–related studies for the Institution University of Ulm from the European Commission, CHDI Foundation, Medivation, NeuroSearch, Novartis, Medesia, and Amarin. Dr McNees has served as a clinical project manager for Medivation from 2007 to the present. Dr Margolis disclosed funding for this project from Medivation and Pfizer. Dr Noonberg works for Medivation and holds stock in the company. Dr Saft has received honoraria from Temmler Pharma Gmbh & Co KG and payment from the European Huntington's Disease Network for the REGISTRY study, from Novartis Pharmaceuticals Switzerland for the AFQ056 study, from NeuroSearch for the ACR16 Study, and from Siena Biotech for Selisistat studies, as well as research support from Teva Pharma GmbH; no financial interests are related to the material in the manuscript. None of the HORIZON investigators of the Huntington Study Group or the European Huntington's Disease Network has had equity interest or received any personal remuneration from the sponsoring companies since the initiation of the study. All authors completed and submitted the International Committee of Medical Journal Editors form for financial disclosure.
Funding/Support: The study was funded by a grant from Medivation to the University of Rochester and in turn through subcontracts to the participating research sites. The study was also sponsored by Pfizer.
Role of the Sponsors: The sponsors contributed to the design and conduct of the study, interpretation of the data, and review of the article as coauthors of the manuscript.
Group Information: The HORIZON Investigators of the Huntington Study Group and European Huntington's Disease Network are as follows: Steering Committee: Karl Kieburtz (principal investigator),* Georg B. Landwehrmeyer (coprincipal investigator),* Merit Cudkowicz,* E. Ray Dorsey,* Andrew Feigin,* Victoria Hunt,* Elise Kayson,* Michael McDermott,* Sarah Noonberg,* Wendy Seitz,* Paola Soliveri,* Francis Walker.* Participating Sites (investigators and coordinators): Bern, Switzerland: Jean-Marc Burgunder, Irene Romero, Anouk Magara, Yanik Stebler. Birmingham and Solihull Mental Health Foundation, Birmingham and Solihull, England: Hugh Rickards,* Jan Wright, Jenny De Souza. Cambridge Centre for Brain Repair, Cambridge, England: Roger A. Barker, Sarah Mason, Anna Di Pietro,* Anna Goodman, Deidre O’Keeffe. Centre Hospitalier Affilie Universitaire de Québec-Hôpital de l’Enfant-Jésus, Québec City, Québec, Canada: Melanie Langlois, Germain Ferland, Louis Verret. CHUM–Hospital Notre-Dame, Montreal, Québec, Canada: Sylvain Chouinard, Suzanne Paris, Christiane LePage. Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, England: Andrea H. Nemeth, Claire Merritt, Caroline Cox, Therese Astbury, Sarah Murphy. Cleveland Clinic, Cleveland, Ohio: Anwar Ahmed, Patricia St Marie, Rose Anne Berila, Cynthia Kubu.* Colorado Neurological Institute, Englewood: Vicki Segro, Rajeev Kumar, Diane Erickson, Jay Schneiders. Columbia University Medical Center, New York, New York: Steven Frucht, Paula Wasserman, Carol Moskowitz. Duke University, Durham, North Carolina: Burton Scott, Peggy Perry-Trice, Sarah Wyne. Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italy: Paola Soliveri, Dominga Parida, Veronica Redaelli. Gabinet Zabiegowy in Gdansk, Gdansk, Poland: Witold Soltan, Piotr Robowski, Malgorzata Nowak,* Michal Schinwelski, Artur Dziadkiewicz. Guy's Hospital, London, England: Thomasin Andrews, Deborah Ruddy, Andrew Dougherty. Hamburg University Hospital, Hamburg, Germany: Kai Boelmans, Jenny Schmalfeld, Alexander Münchau,* Simone Zittel.* Hereditary Neurological Disease Centre, Wichita, Kansas: William Mallonee, Greg Suter, Jeremy Tan. Idaho Elks Rehabilitation Center, Boise: Lauren Seeberger,* Jane Harris, Jamie Champion. Indiana University School of Medicine, Indianopolis: Joanne Wojcieszek, Joann Belden, Katie Price, Marsha Hughes-Gay, Gwen Sprehn. IRCCS Neuromed–Unita di Neurogenetica, Pozzilli, Italy: Ferdinando Squitieri,* Tiziana Martino, Francesca De Gregorio, Annunziata De Nicola, Francesca Elifani. Johns Hopkins University, Baltimore, Maryland: Adam Rosenblatt, Nadine Yoritomo, Russell Margolis,* Paige Nichols.* Karolinska Hospital, Stockholm, Sweden: Sven E. Palhagen, Arja Vehkala Hoglund, Martin Paucar, Tina Wallden Reza-Soltani. Klinik Taufkirchin, München, Germany: Antonie Beister, Tina Raab, Janina Kieni, Caroline Schrenk. Krakow Institution, Krakow, Poland: Krzysztof Banaszkiewicz, Jakub Misztela, Magdalena Wojcik, Elzbieta Szczygiel, Marta Golosz, Monika Rudzińska.* Leiden University Medical Centre, Leiden, the Netherlands: Raymund A. C. Roos, Simon J. A. van den Bogaard, Reineke Bos, Suzanne J. Booij. London Health Sciences Centre, London, England: Christopher Hyson, Julie Megens, Emilija Makaji, Mary Jenkins.* Massachusetts General Hospital, Boston: Steven Hersch, Susan Maya, Caleb Dresser, Diana Rosas. Medical College of Wisconsin, Milwaukee: Karen Blindauer,* Clara Schindler, Serena Hung. Medivation, San Francisco, California: Alexander Aaron McNees.* National Hospital for Neurology and Neurosurgery, London, England: Sarah Tabrizi,* Marianne Novak,* Miranda Say, Aakta Patel. Neurodegenerative Disorders Research, Subiaco, Australia: Peter Panegyres,* Nicola Lewis, Samantha Jukich, Catherine Faull. Neurogenetics Clinic, Copenhagen, Denmark: Lena Elisabeth Hjermind,* Oda Jakobsen,* Asmus Vogel, T. Rune Nielsen, Jørgen E. Nielsen.* Ohio State University, Columbus: Sandra Kostyk,* Allison Seward, Punit Agrawal. Oregon Health & Science University, Portland: Jeff Kraakevik, Penelope Hogarth, April Wilson, Joyce Lear. Rigshospitalet, Copenhagen University Hospital, Memory Disorders Research Unit, Ruhruniversitat Bochum, Copenhagen, Denmark: Peter H. Kraus, Carsten Saft,* Tanja Steiner, Rainer Hoffmann, Christiane Stamm, Joanna Schollhammer, Idun Uhl,* Barbara Kaminski. Sheffield Children's Hospital, Sheffield, England: Kirsty O’Donovan, Oliver Quarrell, Louise Nevitt. Southampton General Hospital, Hampshire, England: Christopher Kipps, Angela Hare, Kerry Gunner, Elaine Hayward. Struthers Parkinson's Center, Golden Valley, Minnesota: Martha Nance,* Judy Hamerlinck, Catherine Wielinski. St Vincent's Aged Psychiatry Service, Melbourne, Australia: Olga Yastrubetskaya, Edmond Chiu,* Phyllis Chua, Bernadette Mannaa. Università di Bari, Bari, Italy: Marina de Tommaso,* Claudia Serpino,* Claudia Cormio, Vittorio Sciruicchio. Università Federico II, Naples, Italy: Giuseppe De Michele,* Luigi Di Maio,* Cinzia Valeria Russo, Francesco Sacca,* Elena Salvatore,* Tecla Tucci. Universitätsklinikum Carl Gustav Carus, Dresden, Germany: Martin Wolz,* Lisa Klingelhöfer,* Annett Wolz, Simone Schmidt, Alexander Storch.* Universitätsklinikum Charité, Berlin, Germany: Eike Spruth, Silvia Thiel, Britta Neumann, Harald Gelderblom, Josef Priller.* University of Aachen, Aachen, Germany: Christian Sass,* Daniela Probst, Cornelius Werner.* University of British Columbia, Vancouver, British Columbia, Canada: Blair R. Leavitt,* Allison Coleman, Lynn Raymond.* University of California, Davis Medical Center: Vicki Wheelock, Teresa Tempkin,* Kathleen Baynes. University of California, Irvine: Neal Hermanowicz,* Shari Niswonger,* Maureen Haske-Palomino. University of California, Los Angeles: Yvette Bordelon, Angelina Gratiano, Arik Johnson. University of California, San Diego: Jody Corey-Bloom,* Jody Goldstein,* Guerry Peavy.* University of California, San Francisco: Michael Geschwind,* Jonathan Gooblar, Cindy Barton. University of Florida, Gainesville: Hubert Fernandez, Ramon Rodriguez, Michele Suelter, Marie Daniels, Janet Romrell,* Camille Swartz. University of Iowa, Iowa City: Leigh Beglinger, Eric Epping,* Elijah Waterman, Megan M. Smith.* University of Kansas Medical Center, Lawrence: Richard Dubinsky, Hilary Dubinsky, Carolyn Gray. University of Manchester, Manchester Academic Health Sciences Centre, and Central Manchester University Hospitals NHS Foundation Trust, Manchester, England: David Craufurd,* Elizabeth Howard, Mary Jones, Helen Murphy. University of Maryland School of Medicine, Baltimore: Karen Anderson, Constance Nickerson, Jennifer De Santo, Tamara Rigaud, Nancy Zappala, Bradley Robottom. University of Miami, Miami, Florida: Carlos Singer,* Monica Quesada, Kenia Rodriguez-Spengler, Rene Hernandez Cardenache. University of Muenster, Muenster, Germany: Ralf Reilmann,* Stefan Bohlen, Eva-Maria Hoelzner. University of Pennsylvania, Philadelphia: Amy Colcher,* Heather Maccarone, Lisa Altin, Andrew Siderowf.* University of Pittsburgh, Pittsburgh, Pennsylvania: Timothy John Greenamyre, Nancy Lucarelli, Larry Ivanco.* University of Rochester, Rochester, New York: Frederick Marshall, Charlyne Hickey, Lisa Deuel, Kevin Biglan. University of Ulm, Ulm, Germany: Sigurd D. Sussmuth, Michael Orth, Sonja Trautmann, Carolin Eschenbach. University of Washington, Seattle: Ali Samii, Alma Macaraeg. USI-MED Poznan, Poznan, Poland: Daniel Zielonka,* Anna Ciesielska, Jerzy T. Marcinkowski,* Justyna Sempolowicz, Hanna Karaskiewicz. Wake Forest University, Winston-Salem, North Carolina: Francis Walker, Christine O’Neill, Ihtsham Haq. Warsaw–IPIN Institute of Psychiatry and Neurology, Warsaw, Poland: Grezegorz Witkowski, Jakub Antczak, Rafal Rola, Przemyslaw Richter, Maria Rakowicz, Katarzyna Jachinska. Washington University, St Louis, Missouri: Susan Criswell, Patricia Deppen, Kathleen Wharton. Westmead Hospital, Sydney, Australia: Neil Mahant,* Elizabeth McCusker,* Jane Griffith, Clement Loy,* Linda Stewart. Biostatistics and Coordination Center: Danielle Fisher,* Dustina Holt,* Constance Orme,* Arthur Watts,* Joseph Weber,* Kathy White.* Safety Monitoring Committee: Robert A. Hauser,* Roger Albin,* Christopher Coffey, Wilhelm Fischer,* Janis Miyasaki.
Additional Contributions: Alexandra Gangler, BA, assisted with the preparation of the manuscript. Michael P. McDermott, PhD, and Arthur Watts, BS, conducted the biostatistical analyses for the study. The Huntington Study Group Coordination and Biostatistics Center at the University of Rochester independently compiled and analyzed the data for this study.
This article was corrected for errors on January 14, 2013.