Yet again, lithium has failed to live up to its promise in the treatment of amyotrophic lateral sclerosis. In a Neurology article posted online August 11, researchers of the LITALS Study Group report on a multicenter trial in Italy, which was deemed futile and stopped early in November 2009.
Adriano Chiò, of the Università degli Studi di Torino in Italy, led this latest effort to follow up on a 2008 report that lithium extended survival in a small cohort (see ARF related news story on Fornai et al., 2008). Another lithium trial was also halted early due to futility in September 2009 (see ARF related news story on Aggarwal et al., 2010).
The Italian group recruited 171 people with ALS and divided them into two treatment arms. One group received the same lithium dose as used in the 2008 trial. The others received half that dose, a level not known to have efficacy in any of lithium’s uses, as a pseudo-placebo. Because many people in the ALS community have pursued lithium prescriptions on their own, it is difficult to recruit subjects for a study including a regular placebo.
By last fall, when more than 85 percent of participants had completed 15 months of therapy or dropped out, the researchers evaluated the results. Between the two treatment groups, there was no difference in people’s ability to breathe on their own or perform daily functions. Compared to historic controls, the authors write, people on lithium may have actually done a bit worse.
People on both doses reported adverse side effects, including neurologic problems, tremors, and thyroid problems. More than one-third of the participants dropped out, either because they experienced unpleasant side effects or perceived no benefit from the therapy.
Is this the last of lithium for ALS? Not quite, according to an editorial penned by Carmel Armon of the Baystate Medical Center in Springfield, Massachusetts. He notes that with no placebo in the study, it is difficult to definitively interpret the results. In addition, two lithium trials are still running: LiCALS and LITRA. Previous trials were designed to find large effects, but these two are aiming for more subtle benefit. “These studies are expected to produce a definitive answer regarding the efficacy of lithium in ALS, or lack thereof,” Armon writes.—Amber Dance
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