title: Impact of the Early Start Denver Model on the cognitive level of children with autism spectrum disorder: study protocol for a randomised controlled trial using a two-stage Zelen design.
abstract: Early intervention for autism spectrum disorder (ASD) in the European French-speaking countries is heterogeneous and poorly evaluated to date. Early intervention units applying the Early Start Denver Model (ESDM) for toddlers and young children with ASD have been created in France and Belgium to improve this situation. It is essential to evaluate this intervention for the political decision-making process regarding ASD interventions in European French-speaking countries. We will evaluate the effectiveness of 12 hours per week ESDM intervention on the cognitive level of children with ASD, over a 2-year period.
  
  
  
  The study will be a multicentre, randomised controlled trial, using a two-stage Zelen design. Children aged 15-36 months, diagnosed with ASD and with a developmental quotient (DQ) of 30 or above on the Mullen Scale of Early Learning (MSEL) will be included. We will use a stratified minimisation randomisation at a ratio 1:2 in favour of the control group. The sample size required is 180 children (120 in the control and 60 in the intervention group). The experimental group will receive 12 hours per week ESDM by trained therapists 10 hours per week in the centre and 2 hours in the toddlers' natural environment (alternatively by the therapist and the parent). The control group will receive care available in the community. The primary outcome will be the change in cognitive level measured with the DQ of the MSEL scored at 2 years. Secondary outcomes will include change in autism symptoms, behavioural adaptation, communicative and productive language level, sensory profile and parents' quality of life. The primary analysis will use the intention-to-treat principle. An economic evaluation will be performed.
  
  
  
  Findings from the study will be disseminated through peer reviewed publications and meetings.
  
  
  
  NCT02608333 (clinicaltrials.gov); Pre-results.
authors.affiliation: Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon F-69003, France.|Laboratoire Health Services and Performance Research, EA 7425 HESPER, Université de Lyon, Lyon F-69008 France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Touzet
authors.affiliation: Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon F-69003, France.|Laboratoire Health Services and Performance Research, EA 7425 HESPER, Université de Lyon, Lyon F-69008 France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Occelli
authors.affiliation: Department of Child and Adolescent Psychiatry, Hopitaux universitaires de Strasbourg, Strasbourg F-67000, France.|CNRS UPR 3212-Team 9, Strasbourg University, Strasbourg F-67000, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Schröder
authors.affiliation: Centre Hospitalier Saint Jean de Dieu, Lyon F-69008, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Manificat
authors.affiliation: Pôle Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, Centre Hospitalier Spécialisé Henri Laborit, Saint Benoît F-86280, France.|Child and Adolescent Psychiatry Department, Unité de Recherche Clinique, Université de Poitiers, Poitiers F-86000, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Gicquel
authors.affiliation: Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Bruxelles 1020, Belgium.
authors.forename: Razvana
authors.initials: R
authors.lastname: Stanciu
authors.affiliation: Office Médico-Pédagogique, University of Geneva, Geneva, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Schaer
authors.affiliation: Service Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, Centre Hospitalier de Versailles, Le Chesnay F-78150, France.
authors.forename: Marie-Joelle
authors.initials: MJ
authors.lastname: Oreve
authors.affiliation: Service Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, Centre Hospitalier de Versailles, Le Chesnay F-78150, France.|EA 4047 HANDIReSP, Université de Versailles Saint-Quentin-en-Yvelines, Versailles F-78000, France.
authors.forename: Mario
authors.initials: M
authors.lastname: Speranza
authors.affiliation: Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon F-69003, France.|Laboratoire Health Services and Performance Research, EA 7425 HESPER, Université de Lyon, Lyon F-69008 France.
authors.forename: Angelique
authors.initials: A
authors.lastname: Denis
authors.affiliation: Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon F-69003, France.|Laboratoire Health Services and Performance Research, EA 7425 HESPER, Université de Lyon, Lyon F-69008 France.
authors.forename: Amelie
authors.initials: A
authors.lastname: Zelmar
authors.affiliation: Université Paris-Sud, CESP, INSERM, UVSQ, Université Paris-Saclay, U1178, Maison de Solenn, Paris cedex 14, France.|Department of Public Health, AP-HP, Hôpital Paul Brousse, Villejuif F-94800, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Falissard
authors.affiliation: Department of child and adolescent psychiatry, Centre Hospitalier le Vinatiers, Bron F-69500, France.|Université de Lyon, Lyon F-69008, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Georgieff
authors.affiliation: EA 4047 HANDIReSP, Université de Versailles Saint-Quentin-en-Yvelines, Versailles F-78000, France.|CIC 1429, INSERM, AP-HP, Hôpital Raymond-Poincare, Garches F-92380, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Bahrami
authors.affiliation: Department of child and adolescent psychiatry, Centre Hospitalier le Vinatiers, Bron F-69500, France.|Université de Lyon, Lyon F-69008, France.
authors.forename: Marie-Maude
authors.initials: MM
authors.lastname: Geoffray
mesh_terms: D000067877:Autism Spectrum Disorder / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy; D001521:Behavior Therapy / Q000379:methods*; D001530:Belgium / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D018479:Early Intervention, Educational; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D012107:Research Design; D016896:Treatment Outcome
keywords: Autism spectrum disorder; Behavior Therapy; Early Start Denver Model; Multicenter Study; Randomized Controlled Trial; Two-stage Zelen design