Measles antibody titers in multiple sclerosis patients and HLA‐matched and unmatched siblings

Abstract

<h3>Objective:</h3> To use a historical placebo control design to determine whether lithium carbonate slows progression of amyotrophic lateral sclerosis (ALS). <h3>Methods:</h3> 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. <h3>Results:</h3> 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, <i>p</i> = 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. <h3>Conclusions:</h3> 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. <h3>Classification of evidence:</h3> 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.