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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | Molecular Autism |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13229-018-0241-5 |
| _version_ | 1818277687854104576 |
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| author | Lucia Capano Annie Dupuis Jessica Brian Deepali Mankad Lisa Genore Rianne Hastie Adams Sharon Smile Toni Lui Dina Odrobina Jane A. Foster Evdokia Anagnostou |
| author_facet | Lucia Capano Annie Dupuis Jessica Brian Deepali Mankad Lisa Genore Rianne Hastie Adams Sharon Smile Toni Lui Dina Odrobina Jane A. Foster Evdokia Anagnostou |
| author_sort | Lucia Capano |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T23:05:30Z |
| format | Article |
| id | doaj.art-9d4d2e0e95b44e6d8a8ff769b807eba5 |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-12-12T23:05:30Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-9d4d2e0e95b44e6d8a8ff769b807eba52022-12-22T00:08:43ZengBMCMolecular Autism2040-23922018-11-019111410.1186/s13229-018-0241-5A pilot dose finding study of pioglitazone in autistic childrenLucia Capano0Annie Dupuis1Jessica Brian2Deepali Mankad3Lisa Genore4Rianne Hastie Adams5Sharon Smile6Toni Lui7Dina Odrobina8Jane A. Foster9Evdokia Anagnostou10Holland Bloorview Kids Rehabilitation Hospital, University of TorontoSick Kids, University of TorontoHolland Bloorview Kids Rehabilitation Hospital, University of TorontoHolland Bloorview Kids Rehabilitation Hospital, University of TorontoHolland Bloorview Kids Rehabilitation HospitalHolland Bloorview Kids Rehabilitation HospitalHolland Bloorview Kids Rehabilitation Hospital, University of TorontoHolland Bloorview Kids Rehabilitation HospitalHolland Bloorview Kids Rehabilitation HospitalSt. Joseph’s Health Care, McMaster UniversityHolland Bloorview Kids Rehabilitation Hospital, University of TorontoAbstract 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.http://link.springer.com/article/10.1186/s13229-018-0241-5PioglitazoneAutism spectrum disorderCytokinesTreatmentClinical trialEfficacy |
| spellingShingle | Lucia Capano Annie Dupuis Jessica Brian Deepali Mankad Lisa Genore Rianne Hastie Adams Sharon Smile Toni Lui Dina Odrobina Jane A. Foster Evdokia Anagnostou A pilot dose finding study of pioglitazone in autistic children Molecular Autism Pioglitazone Autism spectrum disorder Cytokines Treatment Clinical trial Efficacy |
| title | A pilot dose finding study of pioglitazone in autistic children |
| title_full | A pilot dose finding study of pioglitazone in autistic children |
| title_fullStr | A pilot dose finding study of pioglitazone in autistic children |
| title_full_unstemmed | A pilot dose finding study of pioglitazone in autistic children |
| title_short | A pilot dose finding study of pioglitazone in autistic children |
| title_sort | pilot dose finding study of pioglitazone in autistic children |
| topic | Pioglitazone Autism spectrum disorder Cytokines Treatment Clinical trial Efficacy |
| url | http://link.springer.com/article/10.1186/s13229-018-0241-5 |
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