@article{edd362ba7c1b49528f7c24b30acc9125,
title = "Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: Examining a more efficient trial design",
abstract = "Objective: To use a historical placebo control design to determine whether lithium carbonate slows progression of amyotrophic lateral sclerosis (ALS). Methods: A phase II trial was conducted at 10 sites in the Western ALS Study Group using similar dosages (300-450 mg/day), target blood levels (0.3-0.8 mEq/L), outcome measures, and trial duration (13 months) as the positive trial. However, taking riluzole was not a requirement for study entry. Placebo outcomes in patients matched for baseline features from a large database of recent clinical trials, showing stable rates of decline over the past 9 years, were used as historical controls. Results: The mean rate of decline of the ALS Functional Rating Scale-Revised was greater in 107 patients taking lithium carbonate (-1.20/month, 95% confidence interval [CI] -1.41 to -0.98) than that in 249 control patients (-1.01/month, 95% CI -1.11 to -0.92, p = 0.04). There were no differences in secondary outcome measures (forced vital capacity, time to failure, and quality of life), but there were more adverse events in the treated group. Conclusions: The lack of therapeutic benefit and safety concerns, taken together with similar results from 2 other recent trials, weighs against the use of lithium carbonate in patients with ALS. The absence of drift over time and the availability of a large database of patients for selecting a matched historical control group suggest that use of historical controls may result in more efficient phase II trials for screening putative ALS therapeutic agents. Classification of evidence: This study provided Class IV evidence that lithium carbonate does not slow the rate of decline of function in patients with ALS over 13 months.",
author = "Miller, {R. G.} and Moore, {D. H.} and Forshew, {D. A.} and Katz, {J. S.} and Barohn, {R. J.} and M. Valan and Bromberg, {M. B.} and Goslin, {K. L.} and Graves, {M. C.} and McCluskey, {L. F.} and McVey, {A. L.} and T. Mozaffar and Florence, {J. M.} and A. Pestronk and M. Ross and Simpson, {E. P.} and Appel, {S. H.}",
note = "Funding Information: Dr. Miller serves on scientific advisory boards for Cytokinetics, Inc. and Neuraltus Pharmaceuticals, Inc.; has received funding for travel and speaker honoraria from Avanir Pharmaceuticals; serves on the editorial board of Lancet Neurology ; serves as a consultant for Gilead Sciences, Inc.; and receives research support from the Muscular Dystrophy Association. Dr. Moore serves as a consultant for Neuraltus Pharmaceuticals, Inc., Knopp Neurosciences Inc., Sangamo BioSciences, Celgene, and IntelliGeneScan, Inc. and receives research support from Neuraltus Pharmaceuticals, Inc., IntelliGeneScan, Inc., the Phoenix Neurological Association, the Palo Alto Medical Foundation, Knopp Neurosciences Inc., Sangamo BioSciences, the NIH/NCI, and the Muscular Dystrophy Association. D.A. Forshew receives research support from the Muscular Dystrophy Association. Dr. Katz has received research support from Pfizer Inc/Eisai Inc., and the ALS Association, and has received honoraria from Crescent Healthcare, Inc., Blue Cross, Talecris Biotherapeutics, and CSL Behring. Dr. Barohn has served on the speakers' bureau for Talecris Biotherapeutics and receives research support from the NIH. Dr. Valan reports no disclosures. Dr. Bromberg serves on a scientific advisory board for Accordant Health Services, Inc.; has received funding for travel and speaker honoraria from Rx Solutions and Talecris Biotherapeutics; serves as an Assistant Editor for Muscle & Nerve and the Journal of Neuromuscular Diseases and as Editor of Clinical Neurophysiology ; receives publishing royalties for Handbook of Peripheral Neuropathy (Taylor & Francis, 2005) and Quality of Life Measurement in Neurodegenerative and Related Conditions (Cambridge, 2010); serves on the speakers' bureau for Talecris Biotherapeutics; and receives research support from Knopp Neurosciences Inc., and the NIH. Dr. Goslin reports no disclosures. Dr. Graves has served on the speakers' bureau for Talecris Biotherapeutics; has served as a consultant for Avanir Pharmaceuticals, the American Red Cross, Cephalon, Inc., the Guillain-Barr{\'e} Support Group International, and Sanofi-Aventis; receives research support from Regeneron Pharmaceuticals Inc., Avanir Pharmaceuticals, Amgen, Novartis, Genentech, Inc., Sanofi-Aventis, Knopp Neurosciences Inc., the NIH, and the Muscular Dystrophy Association; and is a stakeholder in GE Healthcare. Dr. McCluskey and Dr. McVey report no disclosures. Dr. Mozaffar serves on the Medical and Scientific Advisory Board for the Myositis Association; has served as a consultant and/or on the speakers' bureau for and received funding for travel from Genzyme Corporation, Talecris Biotherapeutics, Crescent Healthcare, Inc., Allergan, Inc., and Avanir Pharmaceuticals, Inc. Dr. Florence serves on a scientific advisory board for Prosensa; serves on the editorial board of Neuromuscular Disorders ; and serves as a consultant for Prosensa, GlaxoSmithKline, and Acceleron Pharma. Dr. Pestronk has served on a speakers' bureau for and received speaker honoraria from Athena Diagnostics, Inc.; owns stock in Johnson & Johnson; is director of the Washington University Neuromuscular Clinical Laboratory which performs antibody testing and muscle and nerve pathology analysis, procedures for which the Washington University Neurology Department bills; may accrue revenue on patents re: TS-HDS antibody, GALOP antibody, GM1 ganglioside antibody, and Sulfatide antibody; has received license fee payments from Athena Diagnostics, Inc. for patents re: antibody testing; and receives/has received research support from Genzyme Corporation, Insmed Inc., Knopp Neurosciences Inc., Prosensa, Isis Pharmaceuticals, Inc., Sanofi-Aventis, the NIH (5R01-NS04326407 [site PI]), CINRG Children's Hospital, Washington, DC, and the Muscular Dystrophy Association. Dr. Ross and Dr. Simpson report no disclosures. Dr. Appel serves on a scientific advisory board for Neuraltus Pharmaceuticals, Inc.; has received a speaker honorarium from Avanir Pharmaceuticals; receives research support from the NIH and the Muscular Dystrophy Association; and has served as an expert consultant in a medico-legal case. ",
year = "2011",
month = sep,
day = "6",
doi = "10.1212/WNL.0b013e31822dc7a5",
language = "English (US)",
volume = "77",
pages = "973--979",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "10",
}