NEW YORK (Reuters Health) – Lithium did not delay the progression of amyotrophic lateral sclerosis (ALS) in a randomized placebo-controlled trial, the investigators reported online April 6 in The Lancet Oncology.

This finding conflicts with promising results from a small pilot study, which led to off-label lithium use by many patients with ALS. Lithium was tested in that 2008 study because it induces clearance of proteins that aggregate in patients with ALS. It did appear to slow disease progression, but there were only 16 patients in the lithium arm and the trial was open-label.

The current double-blinded trial, led by Dr. Swati P. Aggarwal of the Massachusetts General Hospital in Boston, included 84 patients who had been on stable doses of riluzole for at least 30 days. The investigators randomly assigned 40 patients to lithium carbonate and 44 to placebo.

Lithium doses ranged from 150 to 1050 mg/day, titrated to achieve a serum lithium concentration of 0.4 to 0.8 mEq/L (the range used in the pilot study).

The primary endpoint was the time to an event, defined as a decrease of at least six points on the revised ALS functional rating scale score or death. After a decrease of at least six points, patients in the placebo group were switched to lithium.

At the first interim analysis (mean 5.4 months), the study was stopped due to futility. By that point, 22 patients (55%) in the lithium group and 20 (45%) in the placebo group had experienced an event (p = 0.51).

There were no significant differences between groups in the mean decline on the ALS functional rating scale or the quick inventory of depressive symptomatology self-report, or in slow vital capacity.

“At this time, there remains no convincing evidence for the use of lithium as a treatment for patients with ALS,” Dr. Aggarwal and associates conclude.

In an editorial, Dr. Michael Swash of Royal London Hospital, U.K., comments that in the original pilot study, the control group was neither matched nor simultaneously enrolled.

He says that the time-to-event design of the current study, with its potential for rapid results and the possibility of crossover from placebo to treatment, “represents an important advance” in trials of interventions for ALS.

Reference:
Lancet Neurol 2010.