Pioglitazone is a promising compound for treatment of core autism spectrum disorder (ASD) symptoms as it targets multiple relevant pathways, including immune system alterations. 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. 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. 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. 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. ClinicalTrials.gov, NCT01205282 . Registration date: September 20, 2010. 

中文翻译：

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自闭症儿童吡格列酮的初步剂量发现研究

吡格列酮是一种治疗核心自闭症谱系障碍（ASD）症状的有前途的化合物，因为它靶向多种相关途径，包括免疫系统改变。这项初步研究旨在阐明5至12岁自闭症儿童的最大耐受剂量，安全性，疗效的初步证据以及适当的结果指标。我们对吡格列酮进行了为期16周的前瞻性队列，单盲，单臂，2周安慰剂磨合，剂量发现研究。25名参与者完成了治疗。改良的剂量查找方法用于确定三种剂量水平之间的安全性和剂量反应：每天一次0.25 mg / kg，0.5 mg / kg和0.75 mg / kg。最大耐受剂量：没有严重的不良事件（SAE），因此每天测试一次的最大耐受剂量为0.75 mg / Kg。安全性：总体而言，吡格列酮耐受性良好。两名参与者由于感觉无效而中断了干预，而另一名参与者由于无法忍受临时的血液检查而中断了干预。三名参与者经历了轻度中性粒细胞减少症。有效性的早期证据：通过异常行为清单（ABC），儿童耶鲁-布朗强迫症量表（CY-BOCS）和修订的重复性行为量表对社交退缩，重复性行为和外在行为进行了统计学上的显着改善。 （RBS-R）。在这些人中，有46％被认为是全球响应者。吡格列酮具有良好的耐受性，并且在社交退缩，重复性和外在行为的测量中显示出潜在的信号。使用确定剂量的随机对照试验是必要的。ClinicalTrials.gov，NCT01205282。注册日期：2010年9月20日。