Autism Spectrum Disorders
Conditions
Keywords
autism, pervasive developmental disorders, toddlers, behavioral intervention
Brief summary
The major objective of this research protocol is to directly compare two parent intervention conditions of Early Social Interaction (ESI) for 9 months on developmental trajectories of infants showing early risk for Autism Spectrum Disorder (ASD). Participants will be randomized to receive an information, education and support group (Group) ESI intervention offered weekly, or a parent-implemented intervention (Individual) ESI intervention offered in twice-weekly, in combination with the Group ESI intervention.
Detailed description
Mounting evidence exists of the effectiveness of intensive early intervention for a substantial proportion of children with autism spectrum disorders (ASD). Furthermore, age of entry into intervention may be predictive of outcome. Children with ASD in intensive interventions beginning by 3.5 years of age had significantly better outcomes than those beginning after age 5. These findings support the importance of early identification and intervention for improving outcomes. There is very limited research on children with ASD under 3 years of age primarily because the median age for diagnosis in the US is 5.5 years. With advances in earlier screening and diagnosis, there is a pressing need to develop early intervention programs that are appropriate and effective with very young children with ASD. The Early Social Interaction (ESI) Project is an intervention program developed for toddlers at risk for ASD and their families as a model demonstration project funded by the United States Department of Education. ESI was designed to incorporate the National Research Council (NRC) recommendations within the context of a family-centered, natural-environments approach. The major components of ESI are: 1. routines-based intervention in natural environments 2. individualized curriculum 3. parent-implemented intervention The Emory Autism Center of Excellence (ACE) will recruit parent-infant dyads at 12 months of infant's age from a pool of High-Risk for Developing ASD younger siblings and from a pool of low risk infants being studied at the Emory ACE. Parents are involved in the intervention itself while the study outcome measures are focused on the infants that are receiving the different interventions (demographic and outcome data are not collected on the parents of the infants). Infant participants will be randomized to receive an ESI intervention delivered in a group setting, or an individual ESI intervention combined with the group ESI. The intervention will last 9 months and infants will be followed until they reach 36 months of age.
Interventions
BEHAVIORALGroup-ESI
The Group-ESI intervention consists of weekly small group meetings where families receive information about social communication, emotional regulation, play development, and behavioral challenges in toddler playgroups in a relaxed, supportive, child-friendly setting that provides the opportunity to talk with a professional and meet other parents.
BEHAVIORALIndividual-ESI
The Individual-ESI intervention consists of twice-weekly home-based individualized coaching sessions. Parents learn how to support their child's communication, social, and play skills in everyday routines, activities, and places. Individual-ESI begins with an initial home visit, followed by a month of program planning, 6 months of intervention implementation, and 2 months of generalization. During generalization, the clinician meets with the family in a variety of community settings to teach the parent how to implement strategies in new settings.
Sponsors
National Institute of Mental Health (NIMH)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
9 Months to 24 Months
Healthy volunteers
No
Inclusion criteria
* Participants are recruited from the Emory Autism Center of Excellence Center from a pool of younger siblings who are at high or low risk of developing ASD * For high-risk infants, a positive screen on 2 of 4 screening measures indicating the presence of diagnostic features of ASD by 12 months of age * For low-risk infants will be a positive screen on 3 of 4 screening measures * Families agree to twice monthly play group sessions for 9 months and 2-3 intervention sessions per week for 9 months (usually within work-day hours)
Exclusion criteria
* none
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Communication and Symbolic Behavior Scales (CSBS) Score | Baseline (12 months of age, prior to treatment), 15, 21, and 24 months of age | Social communication skills were measured with the Communication and Symbolic Behavior Scales (CSBS) Behavior Sample. Interactions between the child and caregiver were videotaped and later converted to scores. The standardized total score has a mean of 100 and standard deviation of 15. Scores below 100 indicate below average performance with the social, speech, and symbolic composites. |
| Autism Diagnostic Observation Schedule (ADOS) Score | 15, 24, and 36 months of age | Autism symptoms were measured with the Autism Diagnostic Observation Schedule, Second Edition which is the best gold standard diagnostic measure of ASD. The revised algorithms forming Social-Affect and Restricted Repetitive Behavior ratings of autism symptoms were used. A total of score of 1 to 3 indicates no signs of autism, a score of 4 or 5 suggests that the child may have autism spectrum disorder, while a score of 6 to 10 is indicative of autism. |
| Mullen Scales of Early Learning (MSEL) Score | Baseline (12 months of age, prior to treatment), 24, and 36 months of age | The Mullen Scales of Early Learning (MSEL) measures developmental level with standardized scores in five domains: Visual Reception, Receptive Language, Expressive Language, Fine Motor Skills, and Gross Motor Skills. Domain scores are represented in T-scores, with a mean of 50 and standard deviation of 10. A Verbal Composite score is calculated by averaging T-scores of the domains for Receptive and Expressive Language. A Nonverbal Composite score is calculated by averaging T-scores for Visual Reception and Fine Motor domains. Scores below 50 indicate below average performance. |
| Vineland Adaptive Behavior Scales, Second Edition (Vineland II) Score | Baseline (12 months of age, prior to treatment), 24, and 36 months of age | The Vineland II assesses adaptive behavior by providing a standard score in four domains of Communication, Daily Living Skills, Socialization, and Motor Skills. Domain scores and the Adaptive Behavior Composite score are standardized with a mean of 100 with a standard deviation of 15. Scores less than 100 indicate below average performance. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Expressive Language Phase | Baseline (12 months of age, prior to treatment), 15, 21, 24, and 36 months of age | The child's expressive language phase will be determined at each assessment based on the benchmarks delineated by Tager-Flusberg and colleagues and recommended for evaluating the efficacy and comparing outcomes across NIH-funded intervention studies. Based on multiple sources of information about language benchmarks, the language will be categorized as: Preverbal Communication, First Words, Word Combinations, or Sentences, to provide a clinically meaningful measure of language outcome. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Marcus Autism Center in Atlanta, Georgia, USA. Participant enrollment began in May 2013 and follow-up was completed by November 26, 2019.
Pre-assignment details
Infants were enrolled with a parent as parents were a necessary part of the intervention that the infants received. Parents are not considered to be participants who received a study intervention, thus, only infants are described in the modules for Participant Flow, Baseline Characteristics, Outcome Measures, and Adverse Events.
Participants by arm
| Arm | Count |
|---|---|
| Group-ESI Infants 12 months of age at risk of developing ASD who were randomized to receive the Group-ESI intervention for 9 months | 16 |
| Individual-ESI Plus Group-ESI Infants 12 months of age at risk of developing ASD who were randomized to receive Individual-ESI intervention in addition to the Group-ESI intervention for 9 months. | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Group-ESI | Individual-ESI Plus Group-ESI | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 16 Participants | 17 Participants | 33 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 17 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 11 Participants | 23 Participants |
| Region of Enrollment United States | 16 Participants | 17 Participants | 33 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 11 Participants | 11 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 0 / 16 | 0 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Autism Diagnostic Observation Schedule (ADOS) Score
Autism symptoms were measured with the Autism Diagnostic Observation Schedule, Second Edition which is the best gold standard diagnostic measure of ASD. The revised algorithms forming Social-Affect and Restricted Repetitive Behavior ratings of autism symptoms were used. A total of score of 1 to 3 indicates no signs of autism, a score of 4 or 5 suggests that the child may have autism spectrum disorder, while a score of 6 to 10 is indicative of autism.
Time frame: 15, 24, and 36 months of age
Population: This analysis includes participants remaining in the study at the indicated time point who also completed this assessment. Due to scheduling conflicts with families, not all participants were able to complete every study assessment. If a study visit could not be scheduled within the visit window then that visit was skipped and the next assessment was scheduled.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group-ESI | Autism Diagnostic Observation Schedule (ADOS) Score | 15 Months of Age | 3.88 score on a scale | Standard Deviation 2.03 |
| Group-ESI | Autism Diagnostic Observation Schedule (ADOS) Score | 24 Months of Age | 5.14 score on a scale | Standard Deviation 2.69 |
| Group-ESI | Autism Diagnostic Observation Schedule (ADOS) Score | 36 Months of Age | 3.79 score on a scale | Standard Deviation 2.12 |
| Individual-ESI Plus Group-ESI | Autism Diagnostic Observation Schedule (ADOS) Score | 36 Months of Age | 4.53 score on a scale | Standard Deviation 3.56 |
| Individual-ESI Plus Group-ESI | Autism Diagnostic Observation Schedule (ADOS) Score | 15 Months of Age | 3.75 score on a scale | Standard Deviation 2.24 |
| Individual-ESI Plus Group-ESI | Autism Diagnostic Observation Schedule (ADOS) Score | 24 Months of Age | 5.23 score on a scale | Standard Deviation 3 |
Primary
Communication and Symbolic Behavior Scales (CSBS) Score
Social communication skills were measured with the Communication and Symbolic Behavior Scales (CSBS) Behavior Sample. Interactions between the child and caregiver were videotaped and later converted to scores. The standardized total score has a mean of 100 and standard deviation of 15. Scores below 100 indicate below average performance with the social, speech, and symbolic composites.
Time frame: Baseline (12 months of age, prior to treatment), 15, 21, and 24 months of age
Population: This analysis includes participants remaining in the study at the indicated time point who also completed this assessment. Due to scheduling conflicts with families, not all participants were able to complete every study assessment. If a study visit could not be scheduled within the visit window then that visit was skipped and the next assessment was scheduled.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group-ESI | Communication and Symbolic Behavior Scales (CSBS) Score | Baseline (12 months of age, prior to treatment) | 80.44 score on a scale | Standard Deviation 3.83 |
| Group-ESI | Communication and Symbolic Behavior Scales (CSBS) Score | 21 Months of Age | 85.60 score on a scale | Standard Deviation 12.85 |
| Group-ESI | Communication and Symbolic Behavior Scales (CSBS) Score | 15 Months of Age | 79.20 score on a scale | Standard Deviation 10.88 |
| Group-ESI | Communication and Symbolic Behavior Scales (CSBS) Score | 24 Months of Age | 85.79 score on a scale | Standard Deviation 17.48 |
| Individual-ESI Plus Group-ESI | Communication and Symbolic Behavior Scales (CSBS) Score | 15 Months of Age | 80.36 score on a scale | Standard Deviation 8.64 |
| Individual-ESI Plus Group-ESI | Communication and Symbolic Behavior Scales (CSBS) Score | Baseline (12 months of age, prior to treatment) | 78.71 score on a scale | Standard Deviation 5.97 |
| Individual-ESI Plus Group-ESI | Communication and Symbolic Behavior Scales (CSBS) Score | 24 Months of Age | 89.92 score on a scale | Standard Deviation 15.1 |
| Individual-ESI Plus Group-ESI | Communication and Symbolic Behavior Scales (CSBS) Score | 21 Months of Age | 91.20 score on a scale | Standard Deviation 11.81 |
Primary
Mullen Scales of Early Learning (MSEL) Score
The Mullen Scales of Early Learning (MSEL) measures developmental level with standardized scores in five domains: Visual Reception, Receptive Language, Expressive Language, Fine Motor Skills, and Gross Motor Skills. Domain scores are represented in T-scores, with a mean of 50 and standard deviation of 10. A Verbal Composite score is calculated by averaging T-scores of the domains for Receptive and Expressive Language. A Nonverbal Composite score is calculated by averaging T-scores for Visual Reception and Fine Motor domains. Scores below 50 indicate below average performance.
Time frame: Baseline (12 months of age, prior to treatment), 24, and 36 months of age
Population: This analysis includes participants remaining in the study at the indicated time point who also completed this assessment. Due to scheduling conflicts with families, not all participants were able to complete every study assessment. If a study visit could not be scheduled within the visit window then that visit was skipped and the next assessment was scheduled.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group-ESI | Mullen Scales of Early Learning (MSEL) Score | Baseline (12 months of age, prior to treatment) - Nonverbal Composite Score | 54.13 t-score | Standard Deviation 5.66 |
| Group-ESI | Mullen Scales of Early Learning (MSEL) Score | 24 Months of Age - Verbal Composite Score | 40.86 t-score | Standard Deviation 14.2 |
| Group-ESI | Mullen Scales of Early Learning (MSEL) Score | 24 Months of Age - Nonverbal Composite Score | 52.36 t-score | Standard Deviation 6.34 |
| Group-ESI | Mullen Scales of Early Learning (MSEL) Score | 36 Months of Age - Verbal Composite Score | 44.43 t-score | Standard Deviation 12.94 |
| Group-ESI | Mullen Scales of Early Learning (MSEL) Score | 36 Months of Age - Nonverbal Composite Score | 48.93 t-score | Standard Deviation 13.73 |
| Group-ESI | Mullen Scales of Early Learning (MSEL) Score | Baseline (12 months of age, prior to treatment) - Verbal Composite Score | 37.50 t-score | Standard Deviation 8.43 |
| Individual-ESI Plus Group-ESI | Mullen Scales of Early Learning (MSEL) Score | 36 Months of Age - Nonverbal Composite Score | 47.13 t-score | Standard Deviation 10.17 |
| Individual-ESI Plus Group-ESI | Mullen Scales of Early Learning (MSEL) Score | 24 Months of Age - Verbal Composite Score | 45.19 t-score | Standard Deviation 11.02 |
| Individual-ESI Plus Group-ESI | Mullen Scales of Early Learning (MSEL) Score | 36 Months of Age - Verbal Composite Score | 43.63 t-score | Standard Deviation 11.73 |
| Individual-ESI Plus Group-ESI | Mullen Scales of Early Learning (MSEL) Score | Baseline (12 months of age, prior to treatment) - Nonverbal Composite Score | 52.79 t-score | Standard Deviation 8.78 |
| Individual-ESI Plus Group-ESI | Mullen Scales of Early Learning (MSEL) Score | 24 Months of Age - Nonverbal Composite Score | 47.19 t-score | Standard Deviation 10.7 |
| Individual-ESI Plus Group-ESI | Mullen Scales of Early Learning (MSEL) Score | Baseline (12 months of age, prior to treatment) - Verbal Composite Score | 37.03 t-score | Standard Deviation 6.16 |
Primary
Vineland Adaptive Behavior Scales, Second Edition (Vineland II) Score
The Vineland II assesses adaptive behavior by providing a standard score in four domains of Communication, Daily Living Skills, Socialization, and Motor Skills. Domain scores and the Adaptive Behavior Composite score are standardized with a mean of 100 with a standard deviation of 15. Scores less than 100 indicate below average performance.
Time frame: Baseline (12 months of age, prior to treatment), 24, and 36 months of age
Population: This analysis includes participants remaining in the study at the indicated time point who also completed this assessment. Due to scheduling conflicts with families, not all participants were able to complete every study assessment. If a study visit could not be scheduled within the visit window then that visit was skipped and the next assessment was scheduled.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group-ESI | Vineland Adaptive Behavior Scales, Second Edition (Vineland II) Score | Baseline (12 months of age, prior to treatment) | 87.69 score on a scale | Standard Deviation 8.51 |
| Group-ESI | Vineland Adaptive Behavior Scales, Second Edition (Vineland II) Score | 24 Months of Age | 90.64 score on a scale | Standard Deviation 8.91 |
| Group-ESI | Vineland Adaptive Behavior Scales, Second Edition (Vineland II) Score | 36 Months of Age | 90.13 score on a scale | Standard Deviation 10.75 |
| Individual-ESI Plus Group-ESI | Vineland Adaptive Behavior Scales, Second Edition (Vineland II) Score | Baseline (12 months of age, prior to treatment) | 87.19 score on a scale | Standard Deviation 7.26 |
| Individual-ESI Plus Group-ESI | Vineland Adaptive Behavior Scales, Second Edition (Vineland II) Score | 24 Months of Age | 92.14 score on a scale | Standard Deviation 7.08 |
| Individual-ESI Plus Group-ESI | Vineland Adaptive Behavior Scales, Second Edition (Vineland II) Score | 36 Months of Age | 84.57 score on a scale | Standard Deviation 6.21 |
Other Pre-specified
Expressive Language Phase
The child's expressive language phase will be determined at each assessment based on the benchmarks delineated by Tager-Flusberg and colleagues and recommended for evaluating the efficacy and comparing outcomes across NIH-funded intervention studies. Based on multiple sources of information about language benchmarks, the language will be categorized as: Preverbal Communication, First Words, Word Combinations, or Sentences, to provide a clinically meaningful measure of language outcome.
Time frame: Baseline (12 months of age, prior to treatment), 15, 21, 24, and 36 months of age
Population: Expressive language phase was to be coded based on the CSBS, however, this coding requires extensive time and effort by a trained staff member. As the study terminated early and research priorities shifted with the Coronavirus disease 2019 (COVID-19) pandemic, staffing was no longer available to review the video recordings specifically to code language phase. Data analyses for this study focused on addressing the primary aims of the study and data for this outcome were never created.