Clinical trial NCT03388294: Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
Official title: Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autism Spectrum Disorder
Neurodevelopmental Disorders
Keywords: communication
sensory
early intervention
parent coaching
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: University of Southern California
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2018-01-02
Enrollment: 72
Sex: ALL
Minimum age (years): 11
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intervention phases of the study will use a randomized comparative trial design, with two phases. For Study Phase 1, dyads will participate in pretesting; then families will be randomized, stratifying by child age, to one of two treatment arms. Arm 1 families will participate in initial coaching on the PIE sensory reactivity (SR) domain, and Arm 2 families will participate in initial coaching on the PIE prelinguistic communication (PC) domain. Families will participate in 6 weekly coaching sessions in their respective treatment arms, and return for Posttest-1. For Study Phase 2, dyads in Arm 1 will receive 6 weekly coaching sessions on the PC domain, and dyads in Arm 2 will receive 6 weekly coaching sessions on the SR domain. Then families will return for Posttest-2.
Primary purpose: TREATMENT

Brief summary: This study entails a "proof of concept" evaluation of a novel intervention, Parents and Infants Engaged (PIE), for prodromal infants at-risk for neurodevelopmental disorders (NDs). The objectives of the current study are to examine whether the PIE intervention (a) transforms parent-infant transactions over time as intended, thereby facilitating increases in the time infants spend in joint engagement with their parents, and (b) is associated with improved social-communication functioning and positive changes in indices of autonomic self-regulation in infants at-risk for NDs.

Detailed description: Rationale:

Providing intervention during infancy, before the full emergence of the symptoms that would lead to a diagnosis of ND based on a behavioral phenotype (e.g., autism spectrum disorder (ASD), language disorder, or attention-deficit/hyperactivity disorder) is supported by 4 premises: (1) The first two years of life are an especially active period of neural development. Due to rapid synaptic proliferation and experientially-influenced shaping of functional connectivity, interventions initiated in infancy may be powerful in promoting more typical neural connectivity (2) Biologically-based differences in infants at-risk for NDs lead to observable differences in sensory reactivity and communication behaviors in most infants by 9-15 months, prior to the full emergence of diagnostic symptoms. (3) Differences in infant behaviors influence the quantity and quality of parent responses. (4) Parent-child transactional processes begin early in infancy and impact long-term child outcomes. Based on these premises, the investigators propose a "proof of concept" evaluation of a novel intervention, Parents and Infants Engaged (PIE), for prodromal infants at-risk for NDs. PIE is designed to directly impact parent responses to behaviors commonly observed in infants at-risk for NDs. Without intervention, these behaviors may fail to elicit parent responses that efficiently scaffold child communication development. Extensive research shows positive associations between caregiver responsiveness and child communication outcomes. Responsiveness is defined by multiple dimensions (i.e., sensitivity, contingency, encouragement, matching interests/activity level, physical affection, quality of language input \[e.g., verbal scaffolding\], reciprocity, and shared control), which vary within and across caregivers. Children play an active role in eliciting responses from caregivers, emphasizing the co-regulatory or transactional nature of these interactions. This includes biobehavioral co-regulation of arousal levels. Whereas much research comes from studies of typical development, similar transactions occur with young children with NDs. Parent responses vary depending on the preceding behaviors of the child. For example, parents are more likely to respond, and to give a verbal response, to their one-year-olds' gestures than nongestural communicative bids (vocalizations, gaze, actions); also, adults are more likely to respond to infants' speech-like than nonspeech-like vocalizations. Parent responsiveness, in turn, predicts communication outcomes of children with varied NDs.

Aims:

Specific Aim 1: Evaluate the differential changes in attuned parent responsiveness following coaching on two PIE domains - responses to variable infant (a) sensory reactivity (SR) or (b) prelinguistic communication (PC) - as well as cumulative changes in attuned parent responses following coaching on both PIE domains.

Specific Aim 2: Estimate the separate and combined effects of PIE intervention domains on parent-infant engagement and infant-initiated communication with parents.

Specific Aim 3: Determine the extent to which autonomic indices of infant self-regulation change over the course of the PIE intervention.

Recruitment:

To identify infants at-risk for neurodevelopmental disorders, the investigators will use a population-screening method based on birth records in North Carolina, supplemented with distribution of postcards/flyers through physician's offices and public health clinics and email and listserv announcements. Completed First Year Inventories (FYIs) will be scored and screened for risk status. Infants who score at-risk will be flagged, and those families will receive a phone call informing them of the results of the screening (by a qualified/trained project coordinator), and they will be invited for a more comprehensive developmental assessment.

Summary of Measures to be Completed at Each Assessment Time point:

Baseline/Pretest

* Full Mullen Scales of Early Learning (MSEL)
* Sensory Processing Assessment (SPA)
* Brief Observation of Social Communication Change (BOSCC)
* (Respiratory Sinus Arrhythmia (RSA)/ Skin Conductance Level (SCL) Protocol
* Parent-Child Interaction
* Attention Following Protocol
* Sensory Experiences Questionnaire (SEQ)
* MacArthur Bates Communication Development Inventory (MB-CDI)
* Parent Stress Scale

Posttest 1 (6-8 weeks after pretest):

* Parent- Child Interaction
* SEQ

Posttest 2 (13-16 weeks after pretest):

* MSEL Receptive and Expressive Language
* SPA
* BOSCC
* RSA/SCL Protocol
* Parent-Child Interaction
* Attention Following Protocol
* SEQ
* Intervention Rating Profile (intervention group only)

The intervention phases of the study will use a randomized comparative trial design, with two phases. For Intervention Study Phase 1, dyads will participate in the Pretest assessment battery; then the project methodologist will randomize families of eligible infants, stratifying randomization by age (\<13 months, 30 days or ≥ 14 months). Families will be randomized to one of two treatment arms: Arm 1 families will participate in initial coaching on the SR domain of PIE, and Arm 2 families will participate in initial coaching on the PC domain of PIE. Families will participate in 6 coaching sessions in their respective treatment arms, and then return for Posttest-1 (to test the separate impacts of the PIE content domains on parent responses and infant outcomes). For Intervention Study Phase 2, dyads in Arm 1, will receive 6 coaching sessions on the PC domain, and dyads in Arm 2 will receive 6 coaching sessions on the SR domain; coaching for each group will also review their respective content domain coached in Intervention Study Phase 1. Then families will return for Posttest-2 (to evaluate the effects of the full PIE intervention).

Due to COVID-19 restrictions, intervention may be carried out via video-conference platform for no more than one session. Parent-report questionnaires only will be collected in lieu of in-person assessments for Posttest-2 for participants unable to attend in-person.

Data Analyses:

All data will be cleaned and inspected for outliers, missing data and distributional irregularities. Where error distributions potentially deviate from normality, or heteroscedasticity is suspected, the tests of the contrasts will be conducted using exact (resampling-based) nonparametric methods. Proportional outcomes will be arc sin transformed before entering them into the models. For the frequency count outcome, if counts are not sufficiently large (e.g., ≥ 8) that a normal approximation to a Poisson error distribution is appropriate, Poisson or negative binomial regression methods or nonparametric approaches may be employed.

All primary analyses will be conducted to explore a priori contrasts of interest within a repeated measures framework. Of primary interest will be the contrast of Pretest to Posttest-1 scores and the contrast of Pretest to Posttest-2 scores (time effect). In addition, the models will include terms for treatment arm effects and treatment arm-by-time interactions.

At Posttest-1, the investigators anticipate statistically significant time, treatment arm, and arm-by-time interactions, with parents showing differentially greater attuned responses to infant SR or PC, consistent with their respective treatment arm. By Posttest-2, however, the investigators predict group equivalence in responsiveness, with no differential time effects. A follow-up test of the contrast between Posttest-1 and Posttest-2 will verify that parents in Arm 1 maintained their attuned SR responsiveness gains, while parents in Arm 2 "caught up" on attuned SR responsiveness, and vice versa for PC attunement. For H2a, the investigators expect increases in joint engagement from Pretest to Posttest-1, with additional increases at Posttest-2 (time effects), and no differential treatment arm effects or interactions at either Posttest. For H2b, the investigators anticipate minimal increases in infant intentional communication at Posttest-1 in either treatment arm, with comparable improvements (time effects) in each group at Posttest-2. Similarly, on the physiological measures addressing H3a (measured only at Pretest and Posttest-2) the investigators anticipate comparable improvements in RSA and SCL (time effect) in both arms.

Although the investigators are performing multiple statistical tests across outcomes and hypotheses in addressing the specific aims, in this project it is more important to avoid overlooking statistical signals of effectiveness of the innovative PIE intervention approach (Type II errors), than avoiding false assertions of effectiveness (Type I errors). The investigators believe it is premature, therefore, to employ conservative adjustments to the Type I error rates in statistical tests, which would compromise the power of statistical tests to detect such signals. Assuming recruitment of 44 infant-parent dyads and allowing for a 9% (n=4) dropout rate, which is consistent with high retention rates (\> 95%) in our prior intervention studies, 40 dyads (20 per treatment arm) will have complete data for analyses. Assuming a conventional Type I error rate of .05, and intercorrelations among the repeated measures from .3 to .7, the magnitude of treatment group effects detectable with a .80 statistical power will range from f=.37 to .42, respectively, which are large standardized effects. The magnitude of time effects and time-by-treatment arm interaction effects detectable with a .80 power will range from .27 to .18, also respectively, which are medium-sized standardized effects. Thus, the study is underpowered to detect any but large differences between the treatment arms and medium-sized or larger effects on time and time-by treatment arm interactions. More importantly than the statistical comparisons, though, the analyses will yield key descriptive characterizations of the treatment-arm effects at the two posttest points (i.e.,means, medians, proportions, and variances) on key outcomes, as well as effect size estimates that can be used in planning a larger scaled efficacy trial of the PIE intervention.

Eligibility criteria: Inclusion Criteria:

* For the intervention trial: infant must meet risk criteria on the First Years Inventory (Calculated based on data collected in another study where risk status on the FYI was confirmed with follow up at 3 years. We empirically determined combinations of the two FYI domain scores that would sort respondents into "at-risk" and "not-at-risk." The resulting cut-points enabled us to sort children such that we capture about 1/3 of those who would go on to be confirmed as having a autism spectrum diagnosis while misclassifying less than 5% of the typically developing (TD) sample as at-risk). Infants also must score at least one s.d. below the mean on either the Receptive or Expressive subscale t scores AND meet the following SPA inclusion criteria on hyporeactivity (HYPO) or hyperreactivity (HYPER):

  * "HYPO": Cut-point (equal or greater than) of 1.69 for Mean of the raw orienting score across 7 items, each with the range of 1 to 4 possible points)
  * "HYPER": Cut-point (equal or greater than) of .333 for Mean of the raw approach/avoid novel toys score across 9 items, each with the range of 0 to 2 possible points) OR Any clear "defensive" response on orienting items or "Yes" to covering ears to sound (in stereotypies checklist)

Exclusion Criteria:

* families who speak English \< 50% of the time at home
* infants with previously identified genetic disorders (e.g., Down syndrome)
* infants with identified vision/hearing/physical impairments.

Primary outcomes:
measure: Change in Mean Percent of Parent Child Dyadic Engagement Over Time From Baseline to Posttest 1
timeFrame: Baseline, Posttest 1 (6-8 weeks after baseline)
measure: Change in Mean Percent of Parent Child Dyadic Engagement Over Time From Baseline to Posttest 2
timeFrame: Baseline, Posttest 2 (13-16 weeks after baseline)
Secondary outcomes:
measure: Change in Rating of Parent Responsiveness to Child Sensory Reactivity Cues From Baseline to Posttest 1
timeFrame: Baseline, Posttest 1 (6-8 weeks after baseline)
measure: Change in Rating of Parent Responsiveness to Child Sensory Reactivity Cues From Baseline to Posttest 2
timeFrame: Baseline, posttest 2 (13-16 weeks after baseline)
measure: Change in Rating of Parent Responsiveness to Child Prelinguistic Communication Cues From Baseline to Posttest 1
timeFrame: Baseline, Posttest 1 (6-8 weeks after pretest)
measure: Change in Rating of Parent Responsiveness to Child Prelinguistic Communication Cues From Baseline to Posttest 2
timeFrame: Baseline, Posttest 2 (13-16 weeks after baseline)
measure: Change in Rate of Infant Intentional Communication Over Time, Baseline to Posttest 1
timeFrame: Baseline, Posttest 1 (6-8 weeks after pretest)
measure: Change in Rate of Infant Intentional Communication Over Time, Baseline to Posttest 2
timeFrame: Baseline, Posttest 2 (13-16 weeks after pretest)
measure: Change in Respiratory Sinus Arrhythmia From Baseline to Posttest 2 During Social Stimuli
timeFrame: Baseline, Posttest 2 (13-16 weeks after baseline)
measure: Change in Respiratory Sinus Arrhythmia From Baseline to Posttest 2 During Non-Social Stimuli
timeFrame: Baseline, Posttest 2 (13-16 weeks after baseline)
measure: Change in Skin Conductance Levels From Baseline to Posttest 2
timeFrame: Baseline, Posttest 2 (13-16 weeks after baseline)
measure: Change in The Behavioral Observation of Social Communication Change (BOSCC) From Baseline to Posttest 2
timeFrame: Baseline, Posttest 2 (13-16 weeks after baseline)
measure: Change in The Attention Following Protocol (AF Protocol) From Baseline to Posttest 2
timeFrame: Baseline, Posttest 2 (13-16 weeks after baseline)
measure: Change in Mullen Scales of Early Learning Receptive Language T-Scores From Baseline to Posttest 2
timeFrame: Baseline, Posttest 2 (13-16 weeks after baseline)
measure: Change in Mullen Scales of Early Learning Expressive Language T-scores From Baseline to Posttest 2
timeFrame: Baseline, posttest 2 (13-16 weeks after baseline)
measure: Change in Sensory Processing Assessment for Young Children From Baseline to Posttest 2 in Hypo-Reactivity
timeFrame: Baseline, posttest 2 (13-16 weeks after baseline)
measure: Change in Sensory Processing Assessment for Young Children From Baseline to Posttest 2 in Hyper-Reactivity
timeFrame: Baseline, posttest 2 (13-16 weeks after baseline)
measure: Change in The Sensory Experiences Questionnaire Version 2.1 From Baseline to Posttest 1 in Hypo-reactivity
timeFrame: Baseline, posttest 1 (6-8 weeks after baseline)
measure: Change in The Sensory Experiences Questionnaire Version 2.1 From Baseline to Posttest 1 in Hyper-reactivity
timeFrame: Baseline, posttest 1 (6-8 weeks after baseline)
measure: Change in The Sensory Experiences Questionnaire Version 2.1 From Baseline to Posttest 2 in Hypo-reactivity
timeFrame: Baseline, posttest 2 (13-16 weeks after baseline)
measure: Change in The Sensory Experiences Questionnaire Version 2.1 From Baseline to Posttest 2 in Hyper-reactivity
timeFrame: Baseline, Posttest 2 (13-16 weeks after baseline)
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of Southern California
name: Grace T Baranek, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Linda R Watson, EdD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tamis-LeMonda CS, Kuchirko Y, Song L. Why is infant language learning facilitated by parental responsiveness? Current Directions in Psychological Science. 2014;23(2):121-126.
citation: Baranek GT, Watson LR, Turner-Brown L, Field SH, Crais ER, Wakeford L, Little LM, Reznick JS. Preliminary efficacy of adapted responsive teaching for infants at risk of autism spectrum disorder in a community sample. Autism Res Treat. 2015;2015:386951. doi: 10.1155/2015/386951. Epub 2015 Jan 11.
citation: Watson LR, Baranek GT, Roberts JE, David FJ, Perryman TY. Behavioral and physiological responses to child-directed speech as predictors of communication outcomes in children with autism spectrum disorders. J Speech Lang Hear Res. 2010 Aug;53(4):1052-64. doi: 10.1044/1092-4388(2009/09-0096). Epub 2010 Jul 14.
citation: Turner-Brown LM, Baranek GT, Reznick JS, Watson LR, Crais ER. The First Year Inventory: a longitudinal follow-up of 12-month-old to 3-year-old children. Autism. 2013 Sep;17(5):527-40. doi: 10.1177/1362361312439633. Epub 2012 Jul 10.
citation: Guthrie W, Swineford LB, Nottke C, Wetherby AM. Early diagnosis of autism spectrum disorder: stability and change in clinical diagnosis and symptom presentation. J Child Psychol Psychiatry. 2013 May;54(5):582-90. doi: 10.1111/jcpp.12008.
citation: Barnett MA, Gustafsson H, Deng M, Mills-Koonce WR, Cox M. Bidirectional Associations Among Sensitive Parenting, Language Development, and Social Competence. Infant Child Dev. 2012 Jul;21(4):374-393. doi: 10.1002/icd.1750.
citation: Mahoney G, Perales F. Relationship-focused early intervention with children with pervasive developmental disorders and other disabilities: a comparative study. J Dev Behav Pediatr. 2005 Apr;26(2):77-85. doi: 10.1097/00004703-200504000-00002.
citation: Kochanska G, Forman DR, Aksan N, Dunbar SB. Pathways to conscience: early mother-child mutually responsive orientation and children's moral emotion, conduct, and cognition. J Child Psychol Psychiatry. 2005 Jan;46(1):19-34. doi: 10.1111/j.1469-7610.2004.00348.x.
citation: Sameroff AJ, Mackenzie MJ. Research strategies for capturing transactional models of development: the limits of the possible. Dev Psychopathol. 2003 Summer;15(3):613-40. doi: 10.1017/s0954579403000312.
citation: Baker JK, Fenning RM, Howland MA, Baucom BR, Moffitt J, Erath SA. Brief Report: A Pilot Study of Parent-Child Biobehavioral Synchrony in Autism Spectrum Disorder. J Autism Dev Disord. 2015 Dec;45(12):4140-6. doi: 10.1007/s10803-015-2528-0.
citation: Feldman R. Mutual influences between child emotion regulation and parent-child reciprocity support development across the first 10 years of life: Implications for developmental psychopathology. Dev Psychopathol. 2015 Nov;27(4 Pt 1):1007-23. doi: 10.1017/S0954579415000656.
citation: Hill-Soderlund AL, Mills-Koonce WR, Propper C, Calkins SD, Granger DA, Moore GA, Gariepy JL, Cox MJ. Parasympathetic and sympathetic responses to the strange situation in infants and mothers from avoidant and securely attached dyads. Dev Psychobiol. 2008 May;50(4):361-76. doi: 10.1002/dev.20302.
citation: Baranek GT. Autism during infancy: a retrospective video analysis of sensory-motor and social behaviors at 9-12 months of age. J Autism Dev Disord. 1999 Jun;29(3):213-24. doi: 10.1023/a:1023080005650.
citation: Ben-Sasson A, Carter AS. The contribution of sensory-regulatory markers to the accuracy of ASD screening at 12 months. Research in Autism Spectrum Disorders. 2013;7(7):879-888.
citation: Watson LR, Crais ER, Baranek GT, Dykstra JR, Wilson KP. Communicative gesture use in infants with and without autism: a retrospective home video study. Am J Speech Lang Pathol. 2013 Feb;22(1):25-39. doi: 10.1044/1058-0360(2012/11-0145). Epub 2012 Jul 30.
citation: Beauchaine TP, Gatzke-Kopp L, Neuhaus E, Chipman J, Reid MJ, Webster-Stratton C. Sympathetic- and parasympathetic-linked cardiac function and prediction of externalizing behavior, emotion regulation, and prosocial behavior among preschoolers treated for ADHD. J Consult Clin Psychol. 2013 Jun;81(3):481-493. doi: 10.1037/a0032302. Epub 2013 Apr 1.
citation: Lam-Cassettari C, Wadnerkar-Kamble MB, James DM. Enhancing Parent-Child Communication and Parental Self-Esteem With a Video-Feedback Intervention: Outcomes With Prelingual Deaf and Hard-of-Hearing Children. J Deaf Stud Deaf Educ. 2015 Jul;20(3):266-74. doi: 10.1093/deafed/env008. Epub 2015 Mar 28.
citation: Hoivik MS, Lydersen S, Drugli MB, Onsoien R, Hansen MB, Nielsen TS. Video feedback compared to treatment as usual in families with parent-child interactions problems: a randomized controlled trial. Child Adolesc Psychiatry Ment Health. 2015 Feb 12;9:3. doi: 10.1186/s13034-015-0036-9. eCollection 2015.
citation: Beauchaine TP, Neuhaus E, Gatzke-Kopp LM, Reid MJ, Chipman J, Brekke A, Olliges A, Shoemaker S, Webster-Stratton C. Electrodermal responding predicts responses to, and may be altered by, preschool intervention for ADHD. J Consult Clin Psychol. 2015 Apr;83(2):293-303. doi: 10.1037/a0038405. Epub 2014 Dec 8.
citation: Baranek GT, Watson LR, Crais E, Reznick S. First-year inventory (FYI) 2.0. University of North Carolina at Chapel Hill; 2003.
citation: Watson LR, Patten E, Baranek GT, Poe M, Boyd BA, Freuler A, Lorenzi J. Differential associations between sensory response patterns and language, social, and communication measures in children with autism or other developmental disabilities. J Speech Lang Hear Res. 2011 Dec;54(6):1562-76. doi: 10.1044/1092-4388(2011/10-0029). Epub 2011 Aug 23.
citation: Watson LR, Roberts JE, Baranek GT, Yoder P. Respiratory sinus arrhythmia as a predictor of language outcomes in children with autism. International Journal of Psychophysiology. 2012;85(3):348. Accessed 9/28/2015 2:41:37 PM.
citation: Grzadzinski R, Carr T, Colombi C, McGuire K, Dufek S, Pickles A, Lord C. Measuring Changes in Social Communication Behaviors: Preliminary Development of the Brief Observation of Social Communication Change (BOSCC). J Autism Dev Disord. 2016 Jul;46(7):2464-79. doi: 10.1007/s10803-016-2782-9.