| Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: examining a more efficient trial design. | |
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MedLine Citation:
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PMID: 21813790 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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R G Miller; D H Moore; D A Forshew; J S Katz; R J Barohn; M Valan; M B Bromberg; K L Goslin; M C Graves; L F McCluskey; A L McVey; T Mozaffar; J M Florence; A Pestronk; M Ross; E P Simpson; S H Appel; |
Publication Detail:
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Type: Clinical Trial, Phase II; Comparative Study; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-08-03 |
Journal Detail:
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Title: Neurology Volume: 77 ISSN: 1526-632X ISO Abbreviation: Neurology Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-06 Completed Date: 2011-10-31 Revised Date: 2013-03-11 |
Medline Journal Info:
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Nlm Unique ID: 0401060 Medline TA: Neurology Country: United States |
Other Details:
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Languages: eng Pagination: 973-9 Citation Subset: AIM; IM |
Affiliation:
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California Pacific Medical Center, San Francisco, CA, USA. millerrx@sutterhealth.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Amyotrophic Lateral Sclerosis / drug therapy*, pathology* Disease Progression* Female Humans Lithium Carbonate / therapeutic use* Male Mass Screening* / trends Middle Aged Research Design / trends Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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UL1 RR024992/RR/NCRR NIH HHS; UL1 RR024992/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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554-13-2/Lithium Carbonate |
| Investigator | |
Investigator/Affiliation:
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Susan Woolley-Levine / ; Mazen Dimachkie / ; Yunxia Wang / ; E P Bosch / ; Lauren Elman / |
| Comments/Corrections | |
Comment In:
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Neurology. 2011 Sep 6;77(10):936-7
[PMID:
21813782
]
Expert Rev Neurother. 2011 Dec;11(12):1693-8 [PMID: 22091594 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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