#Regress defintion trial#

The median survival time was reported only if the estimated survival probability reached 50%. Mean and median survival durations and 95% confidence intervals (CI) were estimated by using the Kaplan–Meier approach. The slopes of the two linear regression equations of ALSFRS-R scores during the treatment period (ALSFRS-R mean scores over time) were compared using a generalized linear mixed effects model with fixed effects for the time, treatment group, and their interaction ( 4).

This analysis included the assessment of change from the baseline and multivariate Cox regression.

#Regress defintion trial#

The total study duration was 66 weeks, including a 12-week lead-in period and a 54-week treatment period.Ī post-hoc analysis of the entire trial dataset was performed. Briefly, adults with definite ALS (revised El Escorial criteria) who were ≤18 months from symptom onset were randomized 1:1 to receive daily TUDCA (1 g twice daily) or placebo by mouth. Detailed methods have been published ( 1). Participants provided written informed consent before entering the trial. Protocol approval was provided by a central institutional review board for all trial sites. The TUDCA phase II study (NCT00877604) was conducted at three Italian centers. We reviewed the original phase II TUDCA dataset and present here a final intention-to-treat analysis of survival data. Considering that the analysis of the original TUDCA cohort used a univariate approach on individual response variables, there is a need to perform a multivariate approach to increase sensitivity, improve detection of the treatment effect, and allow comparability with other trials. These observations reinforced interest in the potential efficacy of TUDCA as a disease modifier for ALS. Among approved disease-modifying therapies for ALS, only riluzole has been shown to improve tracheostomy-free survival ( 3). Recent phase II pilot studies reported that the administration of tauro-urso-deoxycholic acid (TUDCA) could slow functional decline and increase survival in patients with ALS ( 1, 2). These data further support the disease-modifying effect of TUDCA monotherapy and raise the question of what could be the additional effect of combining TUDCA with sodium phenylbutyrate.Īmyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition with insufficient therapeutic options.

Cox regression analysis demonstrated that placebo treatment was associated with a higher risk of death ( p-value = 0.055). Mean survival time, estimated by the Kaplan–Meier analysis, showed a 1-month difference, favoring active treatment (log-rank test p-value = 0.092). Linear regression slope analysis showed statistical differences in the decline rate, favoring the active treatment arm ( p-value < 0.01 −0.262 for the TUDCA group and −0.388 for the placebo group). We performed a multivariate analysis of the original TUDCA cohort to better define the treatment effect and allow comparability with other trials. Recent phase II pilot clinical trials suggested that tauro-urso-deoxycholic acid (TUDCA) might slow functional decline and increase survival in patients with amyotrophic lateral sclerosis (ALS).

2Department of Neurology, IRCCS Istituto Clinico Humanitas, Milan, Italy.1Department of Biostatistics, Consorzio per Valutazioni Biologiche e Farmacologiche (CVBF), Pavia, Italy.Giorgio Reggiardo 1, Maria Lo Giudice 2, Stefania Lalli 2, Gilberto Rinaldi 3 and Alberto Albanese 2 *