Kong Xue-Jun, Liu Jun, Li Jing, Kwong Kenneth, Koh Madelyn, Sukijthamapan Piyawat, Guo Jason J, Sun Zhenyu Jim, Song Yiqing
1Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, MA USA.
Beth Israel Deaconess Healthcare, Boston, USA.
Pilot Feasibility Stud. 2020 Feb 12;6:20. doi: 10.1186/s40814-020-0557-8. eCollection 2020.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication. Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. () supplementation led to an OXT-dependent behavioral improvement in ASD mouse models. Despite some promising results from animal studies, little is known about the efficacy of supplementation with , alone or with exogenous OXT therapy, on social-behavioral functions in ASD patients. This paper presents a protocol for a pilot randomized controlled trial to evaluate the feasibility of conducting a full trial comparing oral supplementation of probiotics and intranasal OXT spray to placebo on the effect of social and behavioral functions in ASD patients. The study will also capture preliminary estimates of the efficacy of the proposed interventions in ASD patients.
This pilot trial is a two-staged, randomized, double-blind, placebo-controlled, parallel-group study. Throughout the study (0-24 weeks), 60 patients with ASD will be randomly assigned to receive either oral probiotics or placebo. In the second study stage (13-24 weeks), all participants will receive intranasal OXT spray. As primary outcomes, serum OXT levels will be assayed and social behaviors will be assessed via the Autism Behavior Checklist and the Social Responsiveness Scale which are validated questionnaires, an objective emotional facial matching test, and a new video-based eye-tracking test. Secondary outcomes include the GI-severity-index and Bristol Stool Chart to assess GI function and gut microbiome/short-chain fatty acids. All the outcomes will be assessed at baseline and weeks 12 and 24.
This pilot study will provide important information on the feasibility of recruitment, blinding and concealment, treatment administration, tolerability and adherence, specimen collection, outcome assessment, potential adverse effects, and the preliminary efficacy on both primary and secondary outcomes. If successful, this pilot study will inform a larger randomized controlled trial fully powered to examine the efficacies of oral probiotics and/or intranasal OXT spray on social-behavioral improvement in ASD patients.
ClinicalTrials.gov, NCT03337035. Registered 8 November 2017.
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，其特征是社交互动和沟通受损。催产素（OXT）作为一种神经肽，在情感和社交行为中发挥作用。（）补充剂可使ASD小鼠模型出现依赖OXT的行为改善。尽管动物研究取得了一些有前景的结果，但关于单独补充（）或联合外源性OXT治疗对ASD患者社交行为功能的疗效知之甚少。本文介绍了一项初步随机对照试验的方案，以评估进行一项全面试验的可行性，该全面试验将比较口服补充益生菌和鼻内OXT喷雾剂与安慰剂对ASD患者社交和行为功能的影响。该研究还将获取所提议干预措施对ASD患者疗效的初步估计值。
这项初步试验是一项两阶段、随机、双盲、安慰剂对照、平行组研究。在整个研究期间（0至24周），60名ASD患者将被随机分配接受口服益生菌或安慰剂。在研究的第二阶段（13至24周），所有参与者将接受鼻内OXT喷雾剂。作为主要结局指标，将检测血清OXT水平，并通过《自闭症行为检查表》和《社会反应量表》（均为经过验证的问卷）、客观的情感面部匹配测试以及一项基于视频的新眼动追踪测试来评估社交行为。次要结局指标包括胃肠道严重程度指数和布里斯托大便分类法，以评估胃肠道功能以及肠道微生物群/短链脂肪酸。所有结局指标将在基线、第12周和第24周进行评估。
这项初步研究将提供有关招募、设盲和隐藏、治疗实施、耐受性和依从性、样本采集、结局评估、潜在不良反应以及主要和次要结局指标的初步疗效等方面可行性的重要信息。如果成功，这项初步研究将为一项规模更大的随机对照试验提供依据，该试验将有足够的效力来检验口服益生菌和/或鼻内OXT喷雾剂对ASD患者社交行为改善的疗效。
ClinicalTrials.gov，NCT03337035。于2017年11月8日注册。
