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

本研究是法兰克福儿童自闭症谱系障碍早期干预计划(A-FFIP)的第三阶段验证性多中心随机对照试验。A-FFIP是一个基于模型的手动程序。它被归类为一种低频率(每周2小时)的自然发展行为干预(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交沟通的方法。在一项试点对照研究中(N=40)，在一年后发现ADOS比较分数有中等程度的改善。在这里，我们假设，与积极控制组相比，A-FFIP在干预一年后将导致较少的自闭症特有症状。主要纳入标准：自闭症谱系障碍(DSM-5)，年龄2；0-5；6岁，T2；非语言ID/DQ&GT；30。主要终点：在第一次干预后12个月至基线之间的社会沟通变化简明观察总分的绝对变化。BOSCC是从标准化的游戏情景中获得的，测试人员未知，以评估远程社交沟通技能的概括性。它是由独立、可靠的评分机构从视频中盲目评分的。目前的研究在结果衡量标准的选择、探索创新的主持人和调解人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：除了盲目的BOSCC，我们还包括捕捉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，我们研究儿童认知和语言的变化，但超越了将儿童的内化和外化精神病理、执行功能能力以及与父母和家庭相关的措施作为次要结果。主持人：除了儿童的年龄、认知能力和ASD核心症状外，干预开始时通过眼球跟踪客观地评估他/他的社交定向和注意力能力，以及父母的教育状况作为治疗效果的主持人。调节因素：探讨儿童在干预过程中获得的联合注意力、社会互动、认知和精细运动技能以及父母的同步性和治疗依从性，作为ASD核心症状、认知和语言变化的调节因素。质量：通过研究设计将偏倚的风险降至最低。这项研究的执行情况通过两次预审和持续访问进行监测。对所有中心的客观诊断评估和手动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况的设计，并将在有效性、低频调节剂和介体、治疗师和以中心为基础的NDBI方法(包括家长和幼儿园教师)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.