Lithium Tanks in Well-Controlled ALS Trial
In ALS, lithium carbonate is no better than placebo when added to riluzole (Rilutek; sanofi aventis) therapy. The conclusion is based on the fully reported results of a 6-month, multicenter North American study, the details of which are now available in an advanced online issue of the Lancet Neurology. The disappointing findings were originally reported in September of last year, after a planned interim analysis showed no added benefit with the compound.
On the basis of favorable results from a highly publicized Italian pilot study by Fornai et al, Canadian and US researchers randomized lithium and placebo treatment in double-blind fashion to 84 patients with ALS. By using a distinctive time-to-event trial design, researchers would continue the study only if the statistical significance (P value) between treatment-related events equaled .68 or less at an interim analysis.
At a mean treatment duration of 5.4 months,* 22 of 40 (55%) patients receiving lithium and 20 of 44 (45%) patients receiving placebo either died or demonstrated a 6-point score drop on the revised ALS Functional Rating Scale. The statistical significance between the treatment groups was .78—which, according to plan, necessitated discontinuation of the study.
Despite the inefficacy of lithium, which was dosed to achieve blood levels of 0.4-0.8 mEq/L, the drug was reasonably well tolerated. The most common treatment-related adverse events were falls and back pain.
According to the NIH database, there are 5 phase 3 survival trials currently recruiting patients with ALS. Investigated drugs include IM mecobalamin (ie, vitamin B12), the novel agents olesoxime and arimoclomol, and the antibiotic ceftriaxone. Information about active trials can also be found at the ALS Association web site.
ALS = amyotrophic lateral sclerosis.
* The first interim analysis occurred when 84 patients were allocated to treatment, at 6 months or after 55 events, and after 100 events.
Image of lithium carbonate powder from Wikipedia.
