PDF(Pubmed)
Abstract：
This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a clinically and biologically defined subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1\'s mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.
摘要：
本研究旨在评估STP1的安全性和耐受性，专门用于治疗自闭症谱系障碍（ASD）患者的临床和生物学定义的亚组，即ASD表型1（ASD-Phen1）。我们做了一个随机的,双盲,安慰剂对照,平行组1b期研究，两个14天的治疗阶段（在clinicaltrials.gov注册为NCT04644003）。9名ASD-Phen1患者接受STP1治疗，3名患者接受安慰剂治疗。我们评估了安全性和耐受性，以及电生理标记，比如脑电图，听觉习惯,和听觉Chirp同步，更好地理解STP1的作用机制。此外,我们使用了几种临床量表来衡量治疗结果.结果表明，STP1耐受性良好，具有电生理标记物，表明整个大脑以及与执行功能和记忆相关的大脑区域的伽马功率显着降低且剂量相关。用STP1治疗还增加了额叶和枕骨区域的α2功率，并改善了习惯性和听觉chi声的神经同步。尽管在几个临床量表中观察到数值改善，他们没有达到统计学意义。总的来说,这项研究表明,STP1在ASD-Phen1患者中具有良好的耐受性,并显示出在ASD脑区的间接靶向作用.
