Multicentre, randomized controlled trial of the Frankfurt Early Intervention Program for toddlers and preschool aged children with Autism Spectrum Disorder - ASD-FFIP-net

本研究是一项法兰克福早期干预计划的iii期验证性多中心随机对照试验，针对幼儿和学龄前自闭症谱系障碍儿童（a - ffip）。a - ffip是一个手动的、基于模型的程序。它被归类为低频（每周2小时）自然发育行为干预（NDBI），即属于目前被认为最能改善患有自闭症谱系障碍的幼儿和学龄前儿童的社会沟通的方法组。在一项先导对照研究（N=40）中，一年后发现ADOS比较评分有中等程度的改善。在这里，我们假设，与积极对照组相比，A-FFIP在干预一年后会导致更少的自闭症特异性症状。主要入选标准：自闭症谱系障碍（DSM-5）， 2岁；0 - 5；T2时6岁；非言语ID/DQ > 30。主要终点：在基线和第一次干预后12个月的社会沟通变化简短观察（BOSCC）总分的绝对变化。BOSCC是从一个标准化的游戏情境中获得的，有一个未知的测试者来评估远距离社交沟通技能的泛化。它是由一个独立、可靠的评分者从视频中盲目评分的。本研究在结果测量的选择、探索创新的调节因子和调节因子以及确保高研究质量方面超越了以往的随机对照试验。1. 结果：除了盲法BOSCC外，我们还包括捕获社会沟通和重复行为的次要结果。与其他随机对照试验类似，我们研究了儿童认知和语言的变化，但在此基础上，我们将儿童的内化和外化精神病理、执行功能能力以及父母和家庭相关措施作为次要结果。调节因素：除儿童年龄、认知能力、ASD核心症状外，干预开始时通过眼动仪客观评估儿童的社会定向和注意能力，以及父母的教育程度，作为治疗效果的调节因素。3 .中介因素：儿童在干预期间在共同注意、社会交往、认知和精细运动技能、父母同动性和治疗依从性方面的进步是ASD核心症状、认知和语言变化的中介因素。质量：研究设计使偏倚风险最小化。这项研究的执行情况由两次审前和正在进行的访问监测。对所有中心的客观诊断评估和人工干预进行持续培训和监督。综上所述，目前的a - ffip研究选择了一种非常适合当前研究状态的设计，并将在有效性、低频调节因子和中介因子、治疗师和基于中心的NDBI方法（包括父母和幼儿园教师）方面增加新的结果。

The present study is a phase-III confirmatory multicentre, randomized controlled trial of the Frankfurt Early Intervention Program for toddlers and preschool children with Autism Spectrum Disorder (A-FFIP). A-FFIP is a manualised, model-based program. It is classified as a low frequency (2 hrs/week) naturalistic, developmental behavioural intervention (NDBI), i.e. belonging to the group of approaches which currently are considered to best improve social communication in toddlers and preschool-aged children with Autism-Spectrum-Disorder. In a pilot controlled study (N=40), medium improvements in the ADOS comparison score were found after one year. Here, we hypothesize, that A-FFIP will lead to less autism-specific symptoms in the intervention compared to the active control group after one year.Main inclusion criteria: Autism Spectrum Disorder (DSM-5), age 2;0 – 5;6 years old at T2; non-verbal ID/DQ > 30. Primary endpoint: Absolute change in the total score of the Brief Observation of Social Communication Change (BOSCC) between baseline and 12 months after the first intervention session. The BOSCC is obtained from a standardised play situation with an unknown tester to assess generalisation of distant social-communication skills. It is blindly rated from video by an independent, reliable rater.The current study goes beyond previous RCTs regarding the choice of outcome measures, exploring innovative moderators and mediators, and ensuring high study quality. 1. Outcomes: In addition to the blinded BOSCC, we include secondary outcomes capturing social-communication and repetitive behaviour. Similar to other RCTs, we study change in child’s cognition and language, but go beyond by adding the child’s internalising and externalising psychopathology, executive function abilities, and parental and family related measures as secondary outcomes.2. Moderators: In addition to the child’s age, cognitive ability and core ASD symptoms, her/his social orienting and attention abilities objectively assessed by eye-tracking at start of intervention, and parental education status will be explored as moderator of treatment effect.3. Mediators: The child’s gain regarding joint attention, social interaction, cognitive and fine-motor skills during intervention as well as parental synchrony and treatment adherence are explored as mediators of change in core ASD symptoms, cognition and language.4. Quality: Risk of bias is minimized by study design. Execution of the study is monitored by two pre-trial and ongoing visits. Constant training and supervision of objective diagnostic assessment and manual based intervention across all centres. Taken together, the present A-FFIP study has chosen a design which fits very well into the current state of research, and will add new results on efficacy, moderators and mediators of low frequency, therapist and centre based NDBI approaches, including parents and kindergarten teachers into the intervention.