[article] 
inMolecular Autism > 9 (2018) . - 59p.

Titre :	A pilot dose finding study of pioglitazone in autistic children
Type de document :	Texte imprimé et/ou numérique
Auteurs :	L. CAPANO, Auteur ; A. DUPUIS, Auteur ; Jessica BRIAN, Auteur ; D. MANKAD, Auteur ; L. GENORE, Auteur ; R. HASTIE ADAMS, Auteur ; S. SMILE, Auteur ; T. LUI, Auteur ; D. ODROBINA, Auteur ; J. A. FOSTER, Auteur ; Evdokia ANAGNOSTOU, Auteur
Article en page(s) :	59p.
Langues :	Anglais (eng)
Mots-clés :	Autism spectrum disorder  Clinical trial  Cytokines  Drug therapy  Efficacy  Inflammation  Maximum tolerated dose (MTD)  Physiological effects of drugs  Pioglitazone  Safety profile  Treatment
Index. décimale :	PER Périodiques
Résumé :	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.
En ligne :	https://dx.doi.org/10.1186/s13229-018-0241-5
Permalink :	https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

[article] A pilot dose finding study of pioglitazone in autistic children [Texte imprimé et/ou numérique] / L. CAPANO, Auteur ; A. DUPUIS, Auteur ; Jessica BRIAN, Auteur ; D. MANKAD, Auteur ; L. GENORE, Auteur ; R. HASTIE ADAMS, Auteur ; S. SMILE, Auteur ; T. LUI, Auteur ; D. ODROBINA, Auteur ; J. A. FOSTER, Auteur ; Evdokia ANAGNOSTOU, Auteur . - 59p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 59p.

Mots-clés :	Autism spectrum disorder  Clinical trial  Cytokines  Drug therapy  Efficacy  Inflammation  Maximum tolerated dose (MTD)  Physiological effects of drugs  Pioglitazone  Safety profile  Treatment
Index. décimale :	PER Périodiques
Résumé :	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.
En ligne :	https://dx.doi.org/10.1186/s13229-018-0241-5
Permalink :	https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371