Trial Review

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000483156
Ethics application status
Approved
Date submitted
21/03/2019
Date registered
25/03/2019
Date last updated
8/07/2019
Date data sharing statement initially provided
25/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Group-based delivery of a parent-mediated intervention for infants with social communication delay
Scientific title
A randomised controlled trial (RCT) investigating the efficacy of the group-based delivery of a parent-mediated intervention for mitigating autistic symptom severity among infants with social and communication delay
Secondary ID [1] 297761 0
None
Universal Trial Number (UTN)
U1111-1230-3962
Trial acronym
Group-AICES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autism Spectrum Disorder 312103 0
Developmental Language Disorder 312104 0
Condition category
Condition code
Mental Health 310661 310661 0 0
Autistic spectrum disorders
Mental Health 310662 310662 0 0
Learning disabilities
Physical Medicine / Rehabilitation 310663 310663 0 0
Speech therapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This parent-mediated group intervention focuses on enriching social and communication exchanges between an infant and their caregiver. The intervention is delivered by a Research Therapist (i.e., speech pathologist or clinical psychologist), and comprises between 7 and 9 sessions: an initial one-on-one session (1-2 hours) that takes place in the family home two weeks before the group therapy commences, five weekly group-based sessions (2-hours per session), and a follow-up one-on-one booster session (1-2 hours) occurring within a home setting four weeks after the final group therapy session. There is also the option of up to two additional individual booster sessions (at 4-weekly intervals), if required. Group sessions are delivered in a small-group setting (caregivers only) with four to six families per group. Group sessions are attended by parents only. The group intervention uses videotapes of the parent and infant engaging in everyday interactions, which form the basis of a video feedback discussion. The videos included in each session are a mixture of 'stock' videos of parents not involved in the group, and videos of parents involved in the group (recorded during the preceding week). Video feedback provides the opportunity to focus the caregiver’s attention on the infant’s communicative signals and expressions, thereby stimulating skills for observing and empathising with the child. Core methods include: (1) a focus on communicative bids by infants; (2) viewing ‘successful’ excerpts from videotaped interactions, providing positive examples of sensitive parenting; and (3) involvement of a trained therapist to frame observations to assist self-reflection, and to focus behavioural change. Intervention content focuses on enhancing parental observation, attributing communicative intent to infant behaviours that may be difficult to interpret, and facilitating responses that will build infant interaction. The group-based sessions also offer parent-to-parent support, for which there is empirical evidence of the benefits of this type of peer support for families with children with developmental difficulties. As with the Treatment as Usual group, we will also quantify and qualify any contact the families have with other health professionals through a monthly diary completed by parents.
Intervention code [1] 313998 0
Behaviour
Comparator / control treatment
Families in the "treatment as usual" group will receive current treatment protocol offered within the community, which may comprise a 'parent information workshop', the provision of reading material on infant development, or developmental monitoring. Within the "treatment as usual" group, we will quantify all contact with health professionals by asking parents to complete a monthly diary. We will also quantify the nature of this contact by directly contacting the health professional(s) involved.
Control group
Active

Outcomes
Primary outcome [1] 319506 0
The primary outcome is the Autism Observation Scale for Infants (AOSI), which is a measure of the severity of autistic symptoms. The AOSI is a semi-structured observational assessment used to assess the early behavioural expression of ASD. The AOSI examines precursors of later autism symptoms such as response to name, social reciprocity and imitation, as well as items assessing motor and sensory skills. Behaviours are coded 0, 1, 2 and 3 with a higher score indicating a greater level of autistic-like atypicality. The total score is calculated by summing all items in the battery, excluding items 19, 20 and 21, which generates a range of scores from 0 to 38.
Timepoint [1] 319506 0
Baseline assessment will occur within 2 weeks of ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [1] 368506 0
Parent-infant free-play interaction will be filmed at both assessments. Parents will be asked to play with their child as they would usually at home with toys (provided by the study team). Six minute clips were later coded using the Manchester Assessment of Caregiver-Infant interaction (MACI) by a trained coder, blind to family information. Videos recorded at the baseline and treatment endpoint assessments will be coded according to the ‘Infant’ version of the MACI. A secondary outcome for this trial is the Caregiver Sensitive Responsiveness subscale, which is rated on a 7-point scale (ranging from 1-7).
Timepoint [1] 368506 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [2] 368508 0
The Mullen Scales of Early Learning (MSEL) is a standardised developmental assessment, which examines early motor and cognitive development from 0-68 months. Analyses will use subscale T-scores (ranging plausibly from 20-80) unless the data description phase gives evidence of floor-effects, in which case raw scores (ranging plausibly from 0-50) may be used, together with covariation for age at assessment. A secondary outcome for this trial is the Visual Reception subscale of the MSEL.
Timepoint [2] 368508 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [3] 368509 0
The Vineland Adaptive Behavior Scales – 2nd edition (VABS-2) is a parent report measure of daily living skills, which yields scores across a range of ages and competency levels for a range of domains (e.g. motor, communication, personal independence, socialisation). Items are scored on a three-point scale: Never ‘0’, Sometimes ‘1’ or Usually ‘2’, with Don’t Know or No Opportunity responses also possible (and rescored as ‘1’, provided there are not more than two such responses within a given subscale; in which case the subscale score is treated as ‘invalid/missing’). A secondary outcome for this trial will be the Communication subscale of the VABS-2.
Timepoint [3] 368509 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [4] 368510 0
The MacArthur-Bates Communicative Development Inventory (MCDI) is a standardised parent report measure of vocabulary knowledge and other early communication skills appropriate for typical infants aged 8-30 months, but relevant also for older children with language abilities at this level. Two forms exist – Words and Gestures (MCDI-WG) typically for infants aged 8-18 months, and Words and Sentences (MCDI-WS) typically for infants aged 16-30 months. In either form, parents endorse the number of words the child understands, or both understands and says among an inventory spanning different semantic categories (i.e., action words, people etc.) for a plausible total of 396 (WG form) or 680 words (MCDI-WS form). Other subsections of the MCDI pertain to child communicative and symbolic gesture use (i.e., subsections with responses ‘not yet’ [coded 0], and ‘sometimes’ or ‘often’ [both coded 1]) or ‘yes’/’no’ responses [also coded ‘0’ and ‘1’]. A secondary outcome for this trial will be the Expressive Vocabulary Count in the MCDI, which is computed as the total of all ‘understands and says’ items endorsed.
Timepoint [4] 368510 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [5] 368600 0
Parent-infant free-play interaction will be filmed at both assessments. Parents will be asked to play with their child as they would usually at home with toys (provided by the study team). Six minute clips were later coded using the Manchester Assessment of Caregiver-Infant interaction (MACI) by a trained coder, blind to family information. Videos recorded at the baseline and treatment endpoint assessments will be coded according to the ‘Infant’ version of the MACI. A secondary outcome for this trial is the Caregiver Non-directiveness subscale, which is rated on a 7-point scale (ranging from 1-7).
Timepoint [5] 368600 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [6] 368601 0
Parent-infant free-play interaction will be filmed at both assessments. Parents will be asked to play with their child as they would usually at home with toys (provided by the study team). Six minute clips were later coded using the Manchester Assessment of Caregiver-Infant interaction (MACI) by a trained coder, blind to family information. Videos recorded at the baseline and treatment endpoint assessments will be coded according to the ‘Infant’ version of the MACI. A secondary outcome for this trial is the Infant Positive Affect, which is rated on a 7-point scale (ranging from 1-7).
Timepoint [6] 368601 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [7] 368602 0
Parent-infant free-play interaction will be filmed at both assessments. Parents will be asked to play with their child as they would usually at home with toys (provided by the study team). Six minute clips were later coded using the Manchester Assessment of Caregiver-Infant interaction (MACI) by a trained coder, blind to family information. Videos recorded at the baseline and treatment endpoint assessments will be coded according to the ‘Infant’ version of the MACI. A secondary outcome for this trial is the Infant Attentiveness subscale, which is rated on a 7-point scale (ranging from 1-7).
Timepoint [7] 368602 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [8] 368605 0
The Mullen Scales of Early Learning (MSEL) is a standardised developmental assessment, which examines early motor and cognitive development from 0-68 months. Analyses will use subscale T-scores (ranging plausibly from 20-80) unless the data description phase gives evidence of floor-effects, in which case raw scores (ranging plausibly from 0-50) may be used, together with covariation for age at assessment. A secondary outcome for this trial is the Fine motor subscale of the MSEL.
Timepoint [8] 368605 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [9] 368606 0
The Mullen Scales of Early Learning (MSEL) is a standardised developmental assessment, which examines early motor and cognitive development from 0-68 months. Analyses will use subscale T-scores (ranging plausibly from 20-80) unless the data description phase gives evidence of floor-effects, in which case raw scores (ranging plausibly from 0-50) may be used, together with covariation for age at assessment. A secondary outcome for this trial is the Receptive Langauge subscale of the MSEL.
Timepoint [9] 368606 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [10] 368607 0
The Mullen Scales of Early Learning (MSEL) is a standardised developmental assessment, which examines early motor and cognitive development from 0-68 months. Analyses will use subscale T-scores (ranging plausibly from 20-80) unless the data description phase gives evidence of floor-effects, in which case raw scores (ranging plausibly from 0-50) may be used, together with covariation for age at assessment. A secondary outcome for this trial is the Expressive Language subscale of the MSEL.
Timepoint [10] 368607 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [11] 368608 0
The MacArthur-Bates Communicative Development Inventory (MCDI) is a standardised parent report measure of vocabulary knowledge and other early communication skills appropriate for typical infants aged 8-30 months, but relevant also for older children with language abilities at this level. Two forms exist – Words and Gestures (MCDI-WG) typically for infants aged 8-18 months, and Words and Sentences (MCDI-WS) typically for infants aged 16-30 months. In either form, parents endorse the number of words the child understands, or both understands and says among an inventory spanning different semantic categories (i.e., action words, people etc.) for a plausible total of 396 (WG form) or 680 words (MCDI-WS form). Other subsections of the MCDI pertain to child communicative and symbolic gesture use (i.e., subsections with responses ‘not yet’ [coded 0], and ‘sometimes’ or ‘often’ [both coded 1]) or ‘yes’/’no’ responses [also coded ‘0’ and ‘1’]. A secondary outcome for this trial will be the Recepitive Vocabulary Count in the MCDI, which is computed as the total of all 'understands' and ‘understands and says’ items endorsed.
Timepoint [11] 368608 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [12] 368609 0
The MacArthur-Bates Communicative Development Inventory (MCDI) is a standardised parent report measure of vocabulary knowledge and other early communication skills appropriate for typical infants aged 8-30 months, but relevant also for older children with language abilities at this level. Two forms exist – Words and Gestures (MCDI-WG) typically for infants aged 8-18 months, and Words and Sentences (MCDI-WS) typically for infants aged 16-30 months. In either form, parents endorse the number of words the child understands, or both understands and says among an inventory spanning different semantic categories (i.e., action words, people etc.) for a plausible total of 396 (WG form) or 680 words (MCDI-WS form). Other subsections of the MCDI pertain to child communicative and symbolic gesture use (i.e., subsections with responses ‘not yet’ [coded 0], and ‘sometimes’ or ‘often’ [both coded 1]) or ‘yes’/’no’ responses [also coded ‘0’ and ‘1’]. A secondary outcome for this trial will be the Total Gestures score of the MCDI, which is the sum of endorsed items (i.e., coded as 1).
Timepoint [12] 368609 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [13] 368610 0
The Vineland Adaptive Behavior Scales – 2nd edition (VABS-2) is a parent report measure of daily living skills, which yields scores across a range of ages and competency levels for a range of domains (e.g. motor, communication, personal independence, socialisation). Items are scored on a three-point scale: Never ‘0’, Sometimes ‘1’ or Usually ‘2’, with Don’t Know or No Opportunity responses also possible (and rescored as ‘1’, provided there are not more than two such responses within a given subscale; in which case the subscale score is treated as ‘invalid/missing’). A secondary outcome for this trial will be the Socialization subscale of the VABS-2.
Timepoint [13] 368610 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [14] 369911 0
The Diamond Maternal Reflective Functioning Scale is an 18-item self report questionnaire that asks parents questions about reflective functioning in terms of their parenting. The measure has 18 statements, and respondents are asked to answer on a scale from 0 (none or a little time), 1 (some of the time), 2 (a good part of the time), and 3 (most of the time). Scores are summed to create a Total Score.
Timepoint [14] 369911 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [15] 369912 0
The Parental Reflective Functioning Questionnaire (PRFQ) is a short, 18 item, self report measure of parental reflective functioning . This outcome is the Prementalizing subscale, which is designed to assess inability of the parent to acknowledge their child’s mental states.
Timepoint [15] 369912 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [16] 369913 0
The Parental Reflective Functioning Questionnaire (PRFQ) is a short, 18 item, self report measure of parental reflective functioning . This outcome is the Certainty About Mental States subscale, which measures how certain caregivers are about the mental states of their child and their ability/inability to recognise the opacity of mental states.
Timepoint [16] 369913 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [17] 369914 0
The Parental Reflective Functioning Questionnaire (PRFQ) is a short, 18 item, self report measure of parental reflective functioning . This outcome is the Interest and Curiosity subscale, which assesses caregiver interest and curiosity in their child’s mental states.
Timepoint [17] 369914 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [18] 369915 0
The Communication and Symbolic Behaviour Scales - Developmental Profile (CSBS-SP behavioural sample) will be used to assess delays in social communication, expressive speech/language, and symbolic functioning. This outcome is the Social subscale.
Timepoint [18] 369915 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [19] 369916 0
The Communication and Symbolic Behaviour Scales - Developmental Profile (CSBS-SP behavioural sample) will be used to assess delays in social communication, expressive speech/language, and symbolic functioning. This outcome is the Speech subscale.
Timepoint [19] 369916 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).
Secondary outcome [20] 369917 0
The Communication and Symbolic Behaviour Scales - Developmental Profile (CSBS-SP behavioural sample) will be used to assess delays in social communication, expressive speech/language, and symbolic functioning. This outcome is the Symbolic subscale.
Timepoint [20] 369917 0
Baseline assessment will occur after ascertaining study eligibility. The primary outcome will be assessed at treatment endpoint (6 months post-baseline assessment).

Eligibility
Key inclusion criteria
Infants will be offered participation in this trial if they:
(a) Are between 7 months, 0 days and 14 months, 31 days of age (corrected for those infants born <37 weeks gestation);
(b) Endorsement of three or more of the ‘key items’ on the 8-month (for infants 7mo, 0 days – 10mo, 31 days) or 12-month (for infants 11mo, 0 days – 14mo, 31 days) SACS-R.
(c) The primary caregiver involved in the trial speaks sufficient English to: (i) understand the requirements of the study, and (ii) is deemed to be able to participate fully in the therapy sessions.
Minimum age
7 Months
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants will be excluded from the study if they meet any of the following characteristics:
(a) The infant has a diagnosed comorbidity known to affect neurological and developmental abilities (e.g., preterm birth < 32 weeks, cerebral palsy, Down syndrome, Rett syndrome, other chromosomal abnormality, hearing/visual impairment), and/or
(b) The family does not intend to remain living in the Perth area for the next 12 months.
(c) Any active court proceedings or special care arrangements (e.g., children in care of the state or situations where there is not a consistent, long-term caregiver) that may impact on participation in the study

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)
Baseline assessments will be undertaken prior to randomisation to a treatment condition. Following the baseline assessment, participants’ details will be sent to the randomisation site (Telethon Kids Institute) for assignment to either the Treatment as Usual or Experimental Group by the trial coordinator based on a computer algorithm. Once a group has been allocated to a participant, its corresponding code will be recorded in the participants’ electronic file. The trial coordinator is not involved in testing any participants. These codes will be held in password-protected electronic database on a password protected server at the Telethon Kids Institute.

Research assistants conducting the baseline and treatment endpoint assessments will be kept blind to treatment status and study hypotheses throughout the duration of the trial. The primary outcome measure (AOSI) will be coded via videotape by a researcher blind to case details and treatment status. A random 20% of AOSI assessments will be double-coded by a blinded expert. Bias due to therapist effects will be minimised by checks on therapist fidelity. All treatment sessions are videotaped. 5% of these sessions will be scrutinised by independent clinicians against fidelity criteria in the treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will take place at the participant group level; each participant group will consist of exactly four individuals. When ‘every fourth’ (consecutive) individual has undergone their baseline assessment, thus completing a participant group, the trial coordinator will reveal that participant group’s allocation (either the parent mediated group therapy or treatment as usual) as per the randomisation schedule. The randomisation schedule will be prepared using varying blocks of 4 or 6 groups, to ensure study staff are unable to guess subsequent treatment allocations.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


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
Treatment Blinding: The analysis plan has been written prior to the commencement of data collection. All analyses will be undertaken by a biostatistician blind to the treatment group coding.

Data description: The patterns of availability of baseline and follow-up data will be summarised separately for the two treatment groups for each measure. Descriptive summary statistics of means and standard deviations, means and interquartile ranges, and proportions will be presented as appropriate. No statistical significance tests or confidence intervals will be calculated for the difference between randomised groups on any participant-level baseline variables. The randomisation of participants to intervention groups should have ensured that any imbalance over all measured and unmeasured baseline characteristics is due to chance.

Missing data: The pattern of missing data, and the reasons for it, will be described. Analyses of data involving missing outcome measures will be undertaken wherever possible by full information maximum likelihood (ML). The primary approach to handling missing baseline data will be using multiple imputation (MI), carried out using iterative chained equation approach as implemented in R. Both ML and MI allow for potentially selective attrition. Where – for any analysis – complete data cases falls below 70%, complete-case only analyses will also be reported. Where MI is used, complete case analysis will also be carried out and presented for comparison.

Treatment Compliance: The mean and range of the proportion of intervention sessions attended will be reported. The criterion set for minimum compliance is attendance at and completion of 5 sessions.

Effect Estimators: Analysis of the intervention effect element of the study will initially use an intention to treat (ITT) principle, in which participants will be analysed in the groups to which they were randomised utilising all available follow-up data from all randomised participants. Analysis will compare endpoint group effects using a priori hypotheses related to each measurement domain. Where the treatment compliance does not reach the pre-specified ‘minimum’, the Local Average Treatment Effect (LATE) will also be reported for the primary outcome. The LATE approach continues to exploit the randomized to treatment allocation undertaken, and is also valuable in obtaining estimates of mediation unbiased by residual confounding.

Control Variables: Analyses will control for minimisation stratification variables (where ‘age group’ may be replaced with ‘exact age at testing’), variables for which baseline imbalance is suggested, and baseline levels of variable being analysis (where appropriate, ANCOVA model).

Significance and Precision: The analyses specified will use a 5% significance level with 95% confidence intervals. Given the clear hypotheses that are being examined, one-tailed significance testing will be adopted. To reduce multiple testing, significance tests for measures with multiple sub-scores will use global tests with multiple degrees of freedom.

Model checking: For models assuming continuous responses Q-Q plots of residuals will be examined.

The analyses will focus initially on the primary outcome measure (autism symptoms) through an investigation of AOSI Total Scores at the treatment endpoint assessment. AOSI Total Score (dependent variable) is a continuous variable and will be analysed using regression, with intervention group as the independent variable of interest, and covarying for baseline AOSI Total Score (ANCOVA framework).

Further analyses will focus on the trial’s secondary outcome variables at treatment endpoint.

MACI
The following MACI scores will be investigated: Caregiver sensitive responsiveness, caregiver nondirectiveness, infant attentiveness, and infant positive affect. These will be analysed as a four-outcome regression using an estimating equations approach with unstructured working correlation matrix (equivalent to MANOVA in complete data case) with a 4df significance test reported, again with treatment group as the independent variable, and covarying for baseline measures.

MSEL Receptive Language, Expressive Language, Visual Reception, and Fine Motor subscales
The distribution of the endpoint T-scores on the Receptive Language, Expressive Language, Visual Reception, and Fine Motor subscales will be examined for evidence of floor effects. In their absence, these variables will be analysed as a two-outcome regression using an estimating equations approach with unstructured working correlation matrix (equivalent to MANOVA in complete data case) with a 2df significance test reported, again with treatment group as the independent variable of interest, and covarying for baseline measures. Where floor effects are evident – even for raw scores – separate tobit regressions will be estimated. Analyses may or may not covary for baseline scores.

CSBS
The distribution of the endpoint standard scores on the Social, Speech and Symbolic , subscales will be examined for evidence of floor effects. In their absence, these variables will be analysed as a three-outcome regression using an estimating equations approach with unstructured working correlation matrix (equivalent to MANOVA in complete data case) with a 2df significance test reported, again with treatment group as the independent variable of interest, and covarying for baseline measures. Where floor effects are evident – even for raw scores – separate tobit regressions will be estimated. Analyses may or may not covary for baseline scores.

VABS-2 Communication and Socialization domains
The distribution of the endpoint VABS-2 Communication and Socialization domain Standard Scores will be examined for evidence of floor effects. In their absence, the Standard Scores will be analysed as a two-outcome regression using an estimating equations approach with unstructured working correlation matrix (equivalent to MANOVA in complete data case) with a 2df significance test reported. Where floor effects are evident, separate tobit regressions will be estimated, and analyses will not covary for baseline VABS-2 scores.

MCDI
Receptive Vocabulary Count, Expressive Vocabulary Count, Total Gestures score
For receptive and expressive vocabulary counts, analysis will follow the same pattern as for MSEL. However, there will be no covariation for baseline scores. Total gesture score will be analysed as a continuous variable using ANCOVA, with intervention group as the independent variable, and covarying for baseline total score.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/05/2019
Actual
13/05/2019
Date of last participant enrolment
Anticipated
31/08/2020
Actual
Date of last data collection
Anticipated
30/06/2021
Actual
Sample size
Target
80
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 302285 0
Government body
Name [1] 302285 0
Telethon-Perth Children's Hospital Research Fund
Country [1] 302285 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Telethon Kids Institute
Address
Northern Entrance
Perth Children's Hospital
15 Hospital Ave
Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 302166 0
None
Name [1] 302166 0
Address [1] 302166 0
Country [1] 302166 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302962 0
Child and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [1] 302962 0
Ethics committee country [1] 302962 0
Australia
Date submitted for ethics approval [1] 302962 0
12/02/2019
Approval date [1] 302962 0
11/04/2019
Ethics approval number [1] 302962 0
RGS0000003047

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91990 0
Prof Andrew Whitehouse
Address 91990 0
Northern Entrance
Perth Children's Hospital
15 Hospital Ave
Nedlands
WA 6009
Country 91990 0
Australia
Phone 91990 0
+61 8 6319 1000
Fax 91990 0
Email 91990 0
Andrew.Whitehouse@telethonkids.org.au
Contact person for public queries
Name 91991 0
Alena Clark
Address 91991 0
Northern Entrance
Perth Children's Hospital
15 Hospital Ave
Nedlands
WA 6009
Country 91991 0
Australia
Phone 91991 0
+61 8 6319 1000
Fax 91991 0
Email 91991 0
Alena.Clark@telethonkids.org.au
Contact person for scientific queries
Name 91992 0
Alena Clark
Address 91992 0
Northern Entrance
Perth Children's Hospital
15 Hospital Ave
Nedlands
WA 6009
Country 91992 0
Australia
Phone 91992 0
+61 8 6319 1000
Fax 91992 0
Email 91992 0
Alena.Clark@telethonkids.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and Supplementary Material)
When will data be available (start and end dates)?
Immediately following publication; no end date
Available to whom?
Investigators whose proposed use of the data has been approved by an independent ethical review committee identified for the following purposes:
*Replication studies
*Individual participant data meta-analysis
Available for what types of analyses?
For replication studies and individual participant data meta-analysis
How or where can data be obtained?
Proposals should be directed to the Principal Investigator to gain access (Andrew.Whitehouse@telethonkids.org.au); data requestors will be required to sign a data access agreement.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.