Intensive Intervention for Toddlers With Autism (EARLY STEPS)

• ClinicalTrials.gov Identifier: NCT00698997
• Recruitment Status: Completed
• First Posted: June 17, 2008
• Results First Posted: February 17, 2020
• Last Update Posted: February 17, 2020
• Sponsor: University of California, Davis
• Collaborators: University of Washington; University of Michigan; National Institutes of Health (NIH); University of California, Los Angeles; National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): University of California, Davis

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Autism; Autism Spectrum Disorder
• Interventions: Behavioral: Early Start Denver Model; Behavioral: Standard community care
• Enrollment: 118

Participant Flow

Recruitment Details	Children were recruited from pediatricians, developmental disability settings, and university website postings using IRB-approved materials.
Pre-assignment Details

Arm/Group Title	1 Early Start Denver Model	2 Standard Care Available in the Community
Arm/Group Description	Phase 1 of ESDM intervention: 12 weekly, 1 to 1.5 hr. sessions focused on teaching & coaching parents to use the ESDM in all natural caretaking routines & play periods with their child. Parents are taught & coached on 1 aspect of the ESDM each week in the clinic session, & then practice it at home daily in natural family routines & play. Phase 2: each child in the ESDM was assigned to receive 20 hrs. a week of ESDM intervention in their homes, 50 wks. a year, for 2 years by trained interventionists (ITs). Parents delivered ESDM in natural family routines & play activities as they chose. In addition, children received additional public and or private services as their families chose. Both phases followed published treatment manuals and all treatment was supervised by professionals with ESDM certification.	Standard community care: Treatment and interventions, chosen by families, meeting current standards of community intervention for toddlers with autism and ASD
Period Title: Overall Study
Started	55 [1]	63 [1]
Completed	45 [2]	36 [3]
Not Completed	10	27
Reason Not Completed
Lost to Follow-up	3	0
Withdrawal by Subject	7	27
[1] 1 enrollment; [2] 45 - final participant assessment completed; [3] 36 - final assessment completed

Baseline Characteristics

Arm/Group Title		Early Start Denver Model	Standard Care Available in the Community	Total
Arm/Group Description		Phase 1 of ESDM intervention: 12 weekly, 1 to 1.5 hr. sessions focused on teaching & coaching parents to use the ESDM in all natural caretaking routines & play periods with their child. Parents are taught & coached on 1 aspect of the ESDM each week in the clinic session, & then practice it at home daily in natural family routines & play. Phase 2: each child in the ESDM will receive 25 hrs. a week of ESDM intervention in their homes, 50 wks. a year, for 2 years. 20 hrs. weekly will be delivered by trained interventionists (ITs); 5 hrs. weekly will be delivered by parents. (ITs) will provide ten 2 hour teaching episodes involving play activities per week in the home. Parents will continue to deliver the ESDM in natural family routines & play activities. In addition, each child will receive additional services through public services, or other therapies that the parents may choose, for several more hrs. per week.	Standard community care: Treatment and interventions, chosen by families, meeting current standards of community intervention for toddlers with autism and ASD	Total of all reporting groups
Overall Number of Baseline Participants		55	63	118
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	55 participants	63 participants	118 participants
		20.58 (3.37)	20.70 (3.21)	20.64 (3.29)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	55 participants	63 participants	118 participants
	Female	14 25.5%	12 19.0%	26 22.0%
	Male	41 74.5%	51 81.0%	92 78.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	55 participants	63 participants	118 participants
	Hispanic or Latino	6 10.9%	10 15.9%	16 13.6%
	Not Hispanic or Latino	45 81.8%	49 77.8%	94 79.7%
	Unknown or Not Reported	4 7.3%	4 6.3%	8 6.8%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	55 participants	63 participants	118 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	5 9.1%	2 3.2%	7 5.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 3.6%	5 7.9%	7 5.9%
	White	37 67.3%	43 68.3%	80 67.8%
	More than one race	8 14.5%	9 14.3%	17 14.4%
	Unknown or Not Reported	3 5.5%	4 6.3%	7 5.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	55 participants	63 participants	118 participants
		55	63	118

Outcome Measures

1. Primary Outcome

Title	Language Age Equivalent
Description	Composite language measure consisting of an average of the Expressive Language and the Receptive Language age equivalent scores from the Mullen Scales of Early Learning.The Mullen Scales of Early Learning (MSEL) is a developmental test with five subscales: gross motor, visual reception, fine motor, receptive language, and expressive language. The lower the score on this scale, the more immature the ability; the higher the score, the more mature the ability. Measurements were taken at baseline, 6 months, 12 months, and 24 months and a hierarchical longitudinal growth curve approach used to calculate overall rate of growth during the 24 month period.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Early Start Denver Model	Standard Care Available in the Community
Arm/Group Description:	Early Start Denver Model: Phase 1 of ESDM intervention: 12 weekly, 1 to 1.5 hr. sessions focused on teaching & coaching parents to use the ESDM in all natural caretaking routines & play periods with their child. Parents are taught & coached on 1 aspect of the ESDM each week in the clinic session, & then practice it at home daily in natural family routines & play. Phase 2: each child in the ESDM will receive 25 hrs. a week of ESDM intervention in their homes, 50 wks. a year, for 2 years. 20 hrs. weekly will be delivered by trained interventionists (ITs); 5 hrs. weekly will be delivered by parents. (ITs) will provide ten 2 hour teaching episodes involving play activities per week in the home. Parents will continue to deliver the ESDM in natural family routines & play activities. In addition, each child will receive additional services through public services, or other therapies that the parents may choose, for several more hrs. per week.	Standard community care: Treatment and interventions, chosen by families, meeting current standards of community intervention for toddlers with autism and ASD
Overall Number of Participants Analyzed	55	63
Mean (Standard Deviation); Unit of Measure: language age in months
	39.59 (15.31)	36.09 (14.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1 Early Start Denver Model, Standard Care Available in the Community
	Comments	We used a generalized linear mixed model (GLMM). Change-over-Time was modeled as a linear within-subject effect of time across all observed data for each participant. We fit splines to manage the differing lengths of time in parent-training versus direct treatment. In all analyses, site was included as a categorical covariate to account for potential differences. Effect sizes were reported following Cohen's recommendations as f2.
	Type of Statistical Test	Other
	Comments	Non- equivalence.
Statistical Test of Hypothesis	P-Value	.03
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	slope difference
	Estimated Value	1.01
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Developmental Quotient (DQ)
Description	Overall DQ was calculated by averaging the Time 1 (baseline) age equivalence scores of the two language and two nonverbal subtests from the Mullen Scales of Early Learning (MSEL), dividing by child age in months, and multiplying by 100 to create a quotient score, in order to capture the full range of variability of the sample, since many children fell below the basal standard score. The Mullen Scales of Early Learning (MSEL) is a developmental test with five subscales: gross motor, visual reception, fine motor, receptive language, and expressive language. Gross motor score was not used for the calculations. The lower the score on this scale, the more immature the ability; the higher the score, the more mature the ability. Measurements were taken at baseline, 6 months, 12 months, and 24 months and a hierarchical longitudinal growth curve approach used to calculate overall rate of growth during the 24 month period.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Early Start Denver Model	Standard Care Available in the Community
Arm/Group Description:	Early Start Denver Model: Phase 1 of ESDM intervention: 12 weekly, 1 to 1.5 hr. sessions focused on teaching & coaching parents to use the ESDM in all natural caretaking routines & play periods with their child. Parents are taught & coached on 1 aspect of the ESDM each week in the clinic session, & then practice it at home daily in natural family routines & play. Phase 2: each child in the ESDM will receive 25 hrs. a week of ESDM intervention in their homes, 50 wks. a year, for 2 years. 20 hrs. weekly will be delivered by trained interventionists (ITs); 5 hrs. weekly will be delivered by parents. (ITs) will provide ten 2 hour teaching episodes involving play activities per week in the home. Parents will continue to deliver the ESDM in natural family routines & play activities. In addition, each child will receive additional services through public services, or other therapies that the parents may choose, for several more hrs. per week.	Standard community care: Treatment and interventions, chosen by families, meeting current standards of community intervention for toddlers with autism and ASD
Overall Number of Participants Analyzed	55	63
Mean (Standard Error); Unit of Measure: developmental quotient
	83.09 (26.12)	79.14 (25.58)

3. Secondary Outcome

Title	Adaptive Behavior Age Equivalent Scores
Description	Adaptive behavior age equivalent was characterized by averaging the means of the age equivalents in months of the four domain scores from the Vineland Adaptive Behavior Scales - Second edition (VABS) because the manual does not provide developmental ages corresponding to total scores that could be used to construct quotient scores. Data were provided by parents who were not naïve to group assignment. The Vineland Adaptive Behavior Scales 2 provide a standardized measure of adaptive behavior in four domains: motor, language, social, and activities of daily living. Information is gathered from parents via parent questionnaire. The lower the score on each domain score and the overall score, the more immature the ability; the higher the score, the more mature the ability. Measurements were taken at baseline, 6 months, 12 months, and 24 months and a hierarchical longitudinal growth curve approach used to calculate overall rate of growth during the 24 month period.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Early Start Denver Model	Standard Care Available in the Community
Arm/Group Description:	Early Start Denver Model: Phase 1 of ESDM intervention: 12 weekly, 1 to 1.5 hr. sessions focused on teaching & coaching parents to use the ESDM in all natural caretaking routines & play periods with their child. Parents are taught & coached on 1 aspect of the ESDM each week in the clinic session, & then practice it at home daily in natural family routines & play. Phase 2: each child in the ESDM will receive 25 hrs. a week of ESDM intervention in their homes, 50 wks. a year, for 2 years. 20 hrs. weekly will be delivered by trained interventionists (ITs); 5 hrs. weekly will be delivered by parents. (ITs) will provide ten 2 hour teaching episodes involving play activities per week in the home. Parents will continue to deliver the ESDM in natural family routines & play activities. In addition, each child will receive additional services through public services, or other therapies that the parents may choose, for several more hrs. per week.	Standard community care: Treatment and interventions, chosen by families, meeting current standards of community intervention for toddlers with autism and ASD
Overall Number of Participants Analyzed	55	63
Mean (Standard Deviation); Unit of Measure: months
	39.76 (12.07)	36.69 (14.32)

4. Secondary Outcome

Title	Autism Severity
Description	Autism severity was calculated using the Calibrated Severity Scores, derived by using tables in publications by Gotham, Pickles, & Lord( 2012) (Esler, Bal, Guthrie, Weismer, and Lord, 2015). We identified the severity score listed in the CSS table that was associated with a subject's ADOS-2 total score for the ADOS module that was administered to each subject at each of four time points - at entry into the project, and 6 months, 12 months, and 24 months after enrollment. The ADOS Calibrated Severity Score scale range is 1-10, with lower scores representing milder and less numerous symptoms and higher scores representing more severe and more numerous systems. Scores 1-3 represent few to no ASD symptoms, scores of 4-5 represent mild to moderate symptoms and concerns related to ASD, and scores of 6-10 represent moderate to severe symptom severity.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Early Start Denver Model	2Standard Care Available in the Community
Arm/Group Description:	Early Start Denver Model: Phase 1 of ESDM intervention: 12 weekly, 1 to 1.5 hr. sessions focused on teaching & coaching parents to use the ESDM in all natural caretaking routines & play periods with their child. Parents are taught & coached on 1 aspect of the ESDM each week in the clinic session, & then practice it at home daily in natural family routines & play. Phase 2: each child in the ESDM will receive 25 hrs. a week of ESDM intervention in their homes, 50 wks. a year, for 2 years. 20 hrs. weekly will be delivered by trained interventionists (ITs); 5 hrs. weekly will be delivered by parents. (ITs) will provide ten 2 hour teaching episodes involving play activities per week in the home. Parents will continue to deliver the ESDM in natural family routines & play activities. In addition, each child will receive additional services through public services, or other therapies that the parents may choose, for several more hrs. per week.	Standard Care available in the Community Standard community care: Treatment and interventions, chosen by families, meeting current standards of community intervention for toddlers with autism and ASD
Overall Number of Participants Analyzed	55	63
Mean (Standard Deviation); Unit of Measure: units on a scale
	6.69 (1.96)	6.19 (2.52)

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	1 Early Start Denver Model	Standard Care Available in the Community
Arm/Group Description	Early Start Denver Model: Phase 1 of ESDM intervention: 12 weekly, 1 to 1.5 hr. sessions focused on teaching & coaching parents to use the ESDM in all natural caretaking routines & play periods with their child. Parents are taught & coached on 1 aspect of the ESDM each week in the clinic session, & then practice it at home daily in natural family routines & play. Phase 2: each child in the ESDM will receive 25 hrs. a week of ESDM intervention in their homes, 50 wks. a year, for 2 years. 20 hrs. weekly will be delivered by trained interventionists (ITs); 5 hrs. weekly will be delivered by parents. (ITs) will provide ten 2 hour teaching episodes involving play activities per week in the home. Parents will continue to deliver the ESDM in natural family routines & play activities. In addition, each child will receive additional services through public services, or other therapies that the parents may choose, for several more hrs. per week.	Standard community care: Treatment and interventions, chosen by families, meeting current standards of community intervention for toddlers with autism and ASD
All-Cause Mortality
	1 Early Start Denver Model	Standard Care Available in the Community
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/55 (0.00%)	0/63 (0.00%)
Serious Adverse Events
	1 Early Start Denver Model	Standard Care Available in the Community
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/55 (0.00%)	0/63 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	1 Early Start Denver Model	Standard Care Available in the Community
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/55 (0.00%)	0/63 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Sally Rogers
• Organization: University California Davis
• Phone: 916-703-0264
• EMail: sjrogers@ucdavis.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rogers SJ, Estes A, Lord C, Munson J, Rocha M, Winter J, Greenson J, Colombi C, Dawson G, Vismara LA, Sugar CA, Hellemann G, Whelan F, Talbott M. A Multisite Randomized Controlled Two-Phase Trial of the Early Start Denver Model Compared to Treatment as Usual. J Am Acad Child Adolesc Psychiatry. 2019 Sep;58(9):853-865. doi: 10.1016/j.jaac.2019.01.004. Epub 2019 Jan 24.

Zhou V, Munson JA, Greenson J, Hou Y, Rogers S, Estes AM. An exploratory longitudinal study of social and language outcomes in children with autism in bilingual home environments. Autism. 2019 Feb;23(2):394-404. doi: 10.1177/1362361317743251. Epub 2017 Dec 13.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT00698997
• Other Study ID Numbers: 200816233; 1R01MH081757 ( U.S. NIH Grant/Contract )
• First Submitted: June 12, 2008
• First Posted: June 17, 2008
• Results First Submitted: September 18, 2019
• Results First Posted: February 17, 2020
• Last Update Posted: February 17, 2020