A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis

BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118

Pragmatic aspects of task performance: The case of argumentation.

The study reported in this paper investigated the pragmatic aspects of task-performance in a series of argumentation tasks that 24 Hungarian learners of English performed over a period of two years. The aim of our research project was to determine how task-repetition, the long-term development of language skills, and a short-term focused intervention influenced various pragmatic measures of task-performance such as the pragmalinguistic markers of argumentation, the number of claims, counterclaims, supports and counter-supports. We also analysed how these variables differed when the participants performed the same type of task in their mother tongue. The results showed that in the repeated version of the task, familiarity with the task structure helped learners pay more attention to the informational content of their message, which was reflected in the higher number of supportive moves they produced. Participants were found to have better argumentation skills in their mother tongue and used a wider variety of pragmalinguistic markers than in L2. The language development assumed to have taken place during one year and the argumentation training, however, did not result in better pragmatic and pragmalinguistic performance