The anti-diabetic drug pioglitazone did not improve survival time when tested as an add-on therapy to riluzole in a phase 2 clinical trial of people with amyotrophic lateral sclerosis (ALS).
The trial, which was conducted in Germany, was stopped early "for futility" when interim results showed no effects on survival. (A futility trial is one that is designed to stop at a designated point if it's clear that the drug is not having the intended effect.)
In several studies, pioglitazone has proven protective in mouse models of ALS. Investigators have attributed this effect to pioglitazone's ability to inhibit inflammation in the central nervous system. Inflammation can create a toxic environment and kill motor neurons (the nerve cells lost in ALS), and is suspected to be heavily involved in the ALS disease process.
The phase 2 trial was conducted at 15 sites in Germany, at which 220 people with ALS were randomly assigned to receive either 45 milligrams per day of pioglitazone or a placebo for 18 months, followed by an observation period. All participants also were taking 100 milligrams per day of riluzole (the only drug approved by the U.S. Food and Drug Administration for treatment of ALS). The trial was double-blinded, meaning neither trial participants nor investigators knew who received pioglitazone and who received the placebo.
Interim analysis took place after one year of observation, and final analysis was scheduled to be conducted after two years of observation. The primary outcome being measured was survival time in participants treated with pioglitazone compared to those who received the placebo.
Although pioglitazone was well-tolerated, interim data showed that the drug did not increase survival time and the trial was stopped 23 months after enrollment of the first trial participant.
Trial results were reported online June 8, 2012, in PLoS ONE, by Albert Ludolph and colleagues. To read the full results at no charge, see A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis.
For more information on this trial, see Study of Pioglitazone in Patients with Amyotrophic Lateral Sclerosis; or, enter NCT00690118 into the search box at ClinicalTrials.gov.