Erickson Craig A, Perez-Cano Laura, Pedapati Ernest V, Painbeni Eric, Bonfils Gregory, Schmitt Lauren M, Sachs Hannah, Nelson Meredith, De Stefano Lisa, Westerkamp Grace, de Souza Adriano L S, Pohl Oliver, Laufer Offir, Issachar Gil, Blaettler Thomas, Hyvelin Jean-Marc, Durham Lynn A
Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH 45229, USA.
Biomedicines. 2024 Jun 27;12(7):1430. doi: 10.3390/biomedicines12071430.
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.
本研究旨在评估STP1（异丁司特和布美他尼的组合制剂）针对自闭症谱系障碍（ASD）临床和生物学定义的亚组患者，即ASD表型1（ASD-Phen1）的安全性和耐受性。我们进行了一项随机、双盲、安慰剂对照、平行组1b期研究，有两个14天的治疗阶段（在clinicaltrials.gov上注册为NCT04644003）。9名ASD-Phen1患者接受了STP1治疗，3名患者接受了安慰剂治疗。我们评估了安全性和耐受性，以及电生理指标，如脑电图、听觉习惯化和听觉啁啾同步，以更好地了解STP1的作用机制。此外，我们使用了几个临床量表来衡量治疗结果。结果表明，STP1耐受性良好，电生理指标显示全脑以及与执行功能和记忆相关的脑区中γ功率显著且与剂量相关地降低。STP1治疗还增加了额叶和枕叶区域的α2功率，并改善了对听觉啁啾的习惯化和神经同步。尽管在几个临床量表上观察到了数值上的改善，但未达到统计学意义。总体而言，本研究表明STP1在ASD-Phen1患者中耐受性良好，并在感兴趣的ASD脑区显示出间接的靶点作用。
