A pilot dose finding study of pioglitazone in autistic children

Abstract Background Pioglitazone is a promising compound for treatment of core autism spectrum disorder (ASD) symptoms as it targets multiple relevant pathways, including immune system alterations. Objective This pilot study aimed to elucidate the maximum tolerated dose, safety, preliminary evidence of efficacy, and appropriate outcome measures in autistic children ages 5–12 years old. Methods We conducted a 16-week prospective cohort, single blind, single arm, 2-week placebo run-in, dose-finding study of pioglitazone. Twenty-five participants completed treatment. A modified dose finding method was used to determine safety and dose response among three dose levels: 0.25 mg/kg, 0.5 mg/kg, and 0.75 mg/kg once daily. Results Maximum tolerated dose: there were no serious adverse events (SAEs) and as such the maximum tolerated dose within the range tested was 0.75 mg/Kg once daily. Safety: overall, pioglitazone was well tolerated. Two participants discontinued intervention due to perceived non-efficacy and one due to the inability to tolerate interim blood work. Three participants experienced mild neutropenia. Early evidence of efficacy: statistically significant improvement was observed in social withdrawal, repetitive behaviors, and externalizing behaviors as measured by the Aberrant Behavior Checklist (ABC), Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and Repetitive Behavior Scale–Revised (RBS-R). Forty-six percent of those enrolled were deemed to be global responders. Conclusions and relevance Pioglitazone is well-tolerated and shows a potential signal in measures of social withdrawal, repetitive, and externalizing behaviors. Randomized controlled trials using the confirmed dose are warranted. Trial registration ClinicalTrials.gov, NCT01205282. Registration date: September 20, 2010.

A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting more than 1% of children. It is characterized by social communication deficits and repetitive behaviors/restricted interests. In the absence of any medications known to improve core symptom domains, parents often use complementary alternative treatments, including omega-3 fatty acid supplements. Methods We conducted a 6-month, randomized, placebo controlled trial of omega-3 fatty acid supplements (1.5 g) vs placebo in children 2 to 5 years of age with ASD. Primary outcome measures included the autism composite score of the Pervasive Developmental Disorders Behavioral Inventory (PDDBI) and the externalizing problems score of the Behavior Assessment System for Children (BASC-2). Secondary outcome measures included clinical global improvement (Clinical Global Impression-Improvement (CGI-I)), adaptive function (Vineland Adaptive Behavior Scale (VABS-II)), and language gains (Preschool Language Scale (PLS-4)), as well as safety. Exploratory analysis investigated potential correlations between changes in cytokine profiles and treatment response. Results Thirty-eight participants were randomized in a 1:1 fashion. There was no significant difference between groups on the 0- to 24-week change in PDDBI autism composite scores (p = 0.5). There was a significant group by week interaction on the BASC-2 externalizing problem score, with participants randomized to the treatment group demonstrating worsening scores (p = 0.02). There was no statistically significant week by group effect on either adaptive function (p = 0.09) or language (p = 0.6). Omega-3s were relatively well tolerated. Changes in cytokines during the study did not significantly correlate with treatment response. Conclusions This study does not support high dose supplementation of omega-3 fatty acids in young children with ASD. Trial registration Clinicaltrials.gov NCT01248728 . Registered 22 November 2010

AUT756787_Lay_Abstract – Supplemental material for Prospective cohort study of vitamin D and autism spectrum disorder diagnoses in early childhood

<p>Supplemental material, AUT756787_Lay_Abstract for Prospective cohort study of vitamin D and autism spectrum disorder diagnoses in early childhood by Yamna Ali, Laura N Anderson, Sharon Smile, Yang Chen, Cornelia M Borkhoff, Christine Koroshegyi, Gerald Lebovic, Patricia C Parkin, Catherine S Birken, Peter Szatmari and Jonathon L Maguire; on behalf of the TARGet Kids! Collaboration in Autism</p