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Trial registered on ANZCTR


Registration number
ACTRN12616000592448
Ethics application status
Approved
Date submitted
29/03/2016
Date registered
6/05/2016
Date last updated
6/05/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Developmental and sequenced 1 to 1 educational intervention in children with autism spectrum disorder (ASD): a randomized controlled trial.
Scientific title
Developmental and sequenced one to one educational intervention (DS1-EI) for autism spectrum disorder: a randomized single-blind controlled trial.
Secondary ID [1] 288851 0
ANSM No. 130282B-31
Universal Trial Number (UTN)
U1111-1181-3283
Trial acronym
DS1-EI-ASD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autism Spectrum Disorder 298145 0
Intellectual disability 298146 0
Condition category
Condition code
Mental Health 298309 298309 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Based on what was learned from evidence-based studies, we have developed a novel model named “Developmental and Sequenced one-to-one educational Intervention” (DS1-EI) to deliver 5-9 years children with co-occurring ASD and ID a treatment protocol adapted to school implementation. The treatment protocol was adapted for school implementation by designing it using an educational agenda. The intervention is based on intensity, regular assessments, updating objectives, encouraging spontaneous communication, promoting skills through play with peers, supporting positive behaviours rather than tackling challenging behaviors, providing supervision, capitalizing on teachers’ unique skills, and providing developmental and sequenced learning.

More specifficaly:
(1) Participants randomized in the specific experimental protocol (DS1-EI group) receive 4 mornings per week (each session=2h30) of DS1-EI, while the rest of the week they continue to receive the usual protocol of each site. Given the school holiday calendar in France, participants will receive a maximum of 48 sessions by trimester and 150 sessions per year for a 3-year duration.
(2) The setting is implemented in small classroom with 4 pupils and an adapted environment is proposed. Each child is offered a desk, two chairs (one for the child, one for the adult working with the child), a screen where pictures of the child’s schedule and activities are provided, and a locker with his picture. In contrast to TEACCH (Treatment and Education of Autistic and related Communication handicapped CHildren), The child is sitting with his back close to the wall where the screen stands. The setting includes also (i) a large table for mid-session group collation; (ii) a place offering benches and carpets where to group participants (both children and adults) at the beginning and ending of a session.
(3) The program includes 10h of DS1-EI plus other therapeutic proposals according to each institution (e.g. occupational therapy; speech therapy; social skill group activities).
(4) The program follows developmental rules meaning that training is focused on the nearest expected activity/skill of a given child’s development according to the considered domain.
(5) In terms of timing, the program is sequenced in two ways. The 2h30 sessions follow an anticipated and structured agenda that is presented for each child on the screen. When a novel activity starts, the corresponding pictogram is shown on the child’s desk. Second, teachers are asked to change activities every 10-15 minutes to keep attention from the child and to help him improving in challenging sameness needs.
(6) The program is also personalized and curriculum based and has specific educational objectives. Since DS1-EI is a program implemented in classrooms, both curriculum and objectives follow academic recommendations from the French Ministry for National Education. The curriculum was adapted from the French program for nursery and primary schools and handiscol principles (http://eduscol.education.fr). Performed activities are those recommended for persons with special needs and handicap. They are grouped in 4 domains: mathematics (e.g. organizing stickers), language (e.g. naming objects) and communication (e.g. improving joint attention), intermodality (e.g. using various tools such as paint, pastels, markers...) and autonomy (e.g. waiting one’s turn).
(7) Each classroom for N children is under the responsibility of one ID-specilist teacher helped by (N-1) educational assistants according to the 1 to 1 need of the program. When activities change every 10-15 minutes, the adult supervising the child changes as well. So during a single session, each child interact in average 2 times with each adult.
(8) Adherance and fidelity to the programme is monitored through a one week initial training and monthly supervision of each classroom teacher, assistants and childrens' educational agenda.
Intervention code [1] 294314 0
Behaviour
Comparator / control treatment
Participants in the control group are receiving treatment as usual (TAU). TAU is defined as all therapeutic interventions given to a specific child (e.g. occupational therapy, speech therapy, behavioral therapy, medication etc as provided by each site). We recommend not to change children therapeutic protocol in the TAU-group during the study period unless medical requirement.
Control group
Active

Outcomes
Primary outcome [1] 297787 0
Change in the Psycho-educational profile-3 (PEP-3) score
Timepoint [1] 297787 0
Baseline (T0), T18 and T36 months post intervention completion
Secondary outcome [1] 322236 0
Change in Children Autism Rating scale (CARS) score
Timepoint [1] 322236 0
Baseline (T0), T18 and T36 months post intervention completion
Secondary outcome [2] 322237 0
Change in Vineland II Communication, Adaptation, Socialization and Daily living skills
scores
Timepoint [2] 322237 0
Baseline (T0), T12, T24 and T36 months post intervention completion
Secondary outcome [3] 322238 0
Change in Clinical Global Impression (CGI) severity and improvement scores based on clinician's assessment
Timepoint [3] 322238 0
Baseline (T0), T12, T18, T24 and T36 months post intervention completion
Secondary outcome [4] 322239 0
Change in general functioning assessed using the Child-Global Assessment Functioning (C-GAS) score
Timepoint [4] 322239 0
Baseline (T0), T12, T18, T24 and T36 months post intervention completion
Secondary outcome [5] 322240 0
Change in cognitive functioning, assessed using Kaufman Neuropsychological testing (K-ABC) scores
Timepoint [5] 322240 0
Baseline (T0), T18 and T36 months post intervention completion
Secondary outcome [6] 322241 0
Change in School assessment scores.
The school assessment score follows the curriculum that was adapted from the French program for nursery and primary schools and handiscol principles (http://eduscol.education.fr). It lists a series of abilities that are checked and define as acquired (2 points), being aquired (1 point) and not aquired (0 point).
Regarding academic/educational objectives, they are grouped in four domains: mathematics, language and communication; intermodality and autonomy leading to four scores that are the sum of all the points generated by the specific skills belonging to the corresponding domain.
Timepoint [6] 322241 0
Baseline (T0), T12, T24 and T36 months post intervention completion

Eligibility
Key inclusion criteria
Inclusion criteria :
- a current diagnosis of ASD confirmed by clinical assessment and the Autism Diagnostic Interview-Revised;
- a developmental quotient less than or equal to 24 months;
- no fluent oral language
- aged between 5 to 9 years.
- Controls are matched for sex, age, IQ, study sites before randomization
Minimum age
5 Years
Maximum age
9 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria :
- parents’ refusal to participate;
- family project to change institution in the short term whatever the reason;
- patient’s agitation, hyperactivity or behavioral problems that would challenge presence in classroom.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Before randomization, each site is requested to assess the IQ of the participants based on the KABC-II or, failing that, Vineland scores. Based on these results, dyads of participants matched for sex, age, and DQ are formed to limit the risk of bias between groups. Randomization before group allocation to TAU or DS1-EI group will be performed by drawing lots in each dyad per site so that each site could have a TAU group and a DS1-EI group of 3 to 4 participants each. Randomization will be performed by the methodological coordinating team at the Salpetriere Hospital that is independent from local inclusion sites.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
From previous treatment studies in ASD that showed significant results in terms of efficacy it appears that the minimal number of patients in parallel design was 50. This was the case for behavioural ABA approach (e.g. [Smith et al. Am J Ment Retard 2000; 105:269–285]) or for developmental ESDM approach (e.g. [Dawson et al. Pediatrics 2010,125:e17–e23.]). The number of patients to enrol has been based on the following theoretical statistics estimation: for a moderate effect size (a=0.6), a power fixed at 80%, and a level of significance for a p value fixed at < 0.05, 80 patients randomized into two groups are required for a student-t test. Given our choice to use linear mixed models (see below) to take into account participant’s effect, we planned to recruit from 70 to 80 participants.

Statistical analyses will be performed using R Software, Version 2.12.2. To assess whether improvement occurs in both primary and secondary variables, we will use linear mixed models with change in a given variable explained by group exposure (DS1-EI vs. TAU), time (baseline vs. 18 months vs. 36 months) and their interaction (group exposure x time). We will also include a random effect and a site effect. This should account for individual heterogeneity, site heterogeneity, variable scores at inclusion and change specific to DS1-EI within the same statistical regression. For missing data when available, we will use the last observation carried forward. In case of a non-Gaussian distribution, we will study the log transformation (or other transformation when appropriate) to achieve a normal distribution. Lost or drop-out patients will also be compared between groups using a separate nonparametric comparison.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7749 0
France
State/province [1] 7749 0

Funding & Sponsors
Funding source category [1] 293208 0
Government body
Name [1] 293208 0
Caisse Nationale de Solidarite pour l’Autonomie (CNSA)
Address [1] 293208 0
66 Avenue du Maine, 75014 Paris
Country [1] 293208 0
France
Funding source category [2] 293209 0
Charities/Societies/Foundations
Name [2] 293209 0
Croix Rouge Francaise
Address [2] 293209 0
98 rue Didot, 75014 Paris
Country [2] 293209 0
France
Funding source category [3] 293210 0
Charities/Societies/Foundations
Name [3] 293210 0
Fondation Bettencourt-Schueller
Address [3] 293210 0
27 Rue des Poissonniers, 92200 Neuilly-sur-Seine
Country [3] 293210 0
France
Funding source category [4] 293211 0
Commercial sector/Industry
Name [4] 293211 0
Fondation EDF
Address [4] 293211 0
9 avenue de Percier, 75008, Paris
Country [4] 293211 0
France
Primary sponsor type
Charities/Societies/Foundations
Name
Croix Rouge Francaise
Address
98 rue Didot, 75014 Paris
Country
France
Secondary sponsor category [1] 292010 0
Other Collaborative groups
Name [1] 292010 0
Programme de Recherches et d'Etudes sur l'Autisme
Address [1] 292010 0
1 rue Saint-Antoine, 75011, Paris
Country [1] 292010 0
France

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294693 0
Comite de Protection des Personnes V Ile de France – Hopital Saint-Antoine
Ethics committee address [1] 294693 0
Hopital Saint-Antoine
184 rue du faubourg Saint-Antoine
75012 Paris, France
Ethics committee country [1] 294693 0
France
Date submitted for ethics approval [1] 294693 0
16/04/2013
Approval date [1] 294693 0
07/05/2013
Ethics approval number [1] 294693 0
ANSM 130282B-31

Summary
Brief summary
Despite improvements in the early treatment of children with Autism Spectrum Disorder (ASD), there are still many challenges to face in particular in individuals with ASD that also exhibit severe to moderate ranges of intellectual disability (ID). Based on previous research and the need to offer treatment in natural context such as school, we have developed a novel model named “Developmental and Sequenced one-to-one educational Intervention” (DS1-EI) to deliver 5-9 years children with co-occurring ASD and ID a treatment protocol adapted to school implementation because it is based on educational agenda (autonomy, communication, fine motor skills, mathematics). The major objectives of the study are (1) to select at least 10 French institutions to implement the treatment model; (2) to test the model during a randomized controlled trial over a period of 18 and 36 months.
Each institution will recruit participants per dyads matched for age, sex and developmental quotient. Then patients will be randomized to DS1-EI group or Treatment as usual (TAU) group. During the rehabilitation period, only half of the children will participate in the experimental (DS1-EI) group model designed to improve their developmental abilities and decrease their autism symptoms. Controls will be allocated to TAU. Participants will be assessed at T12, T18, T24 and T36 with a selection of variables. We hope to show a better improvement in the experimental group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64682 0
Dr Jean-Louis Sarradet
Address 64682 0
Programme de Recherches et d'Etudes sur l'Autisme
1, rue Saint Antoine - 75004 Paris
Country 64682 0
France
Phone 64682 0
+339 79 32 86 08
Fax 64682 0
Email 64682 0
jean-louis.sarradet@wanadoo.fr
Contact person for public queries
Name 64683 0
Mrs Delphine Le Molgat
Address 64683 0
Croix Rouge Francaise
98 rue Didot 75014, Paris, France
Country 64683 0
France
Phone 64683 0
+331 44 43 35 71
Fax 64683 0
Email 64683 0
Delphine.LeMolgat@croix-rouge.fr
Contact person for scientific queries
Name 64684 0
Prof David Cohen
Address 64684 0
Department of Child and Adolescent Psychiatry
GH Pitie-Salpetriere
47 bd de l'Hopital 75013, Paris, France
Country 64684 0
France
Phone 64684 0
+33142162351
Fax 64684 0
Email 64684 0
david.cohen@aphp.fr

No information has been provided regarding IPD availability
Summary results
No Results