Heterogeneity in ASD: Biological Mechanisms, Trajectories, and Treatment Response
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | Any |
| Updated: | 10/12/2018 |
| Start Date: | June 15, 2018 |
| End Date: | June 30, 2022 |
| Contact: | Amanda C Gulsrud, PhD |
| Email: | AGulsrud@mednet.ucla.edu |
| Phone: | 3108250575 |
Parent-mediated interventions often target social communication in young children with ASD,
although to date studies yield inconsistent effects. One reason for the limited evidence may
be the considerable heterogeneity in both parent and child characteristics that affect the
fit of intervention to family and ultimately influence treatment outcome. For parents, these
factors might include stress associated with the uncertainty of their child's diagnosis,
caregiver expectations for the intervention itself, and a parent's own style of interaction
that may be influenced by milder but qualitatively similar ASD characteristics, known as the
broad autism phenotype (BAP). For children, these factors might include nonverbal DQ,
language, or sensory impairment. The fit between type of intervention and optimal outcome for
parent and child is an understudied, yet essential component of early intervention that may
be susceptible to the influence of heterogeneity in the parent and child. One approach to
addressing this variability is to implement an adaptive intervention approach that seeks to
capitalize on heterogeneity among children and parents. Utilizing an adaptive treatment
design, the current study tests the optimal sequence of intervention delivery and specific
parent and child characteristics that may moderate treatment success in three 10-week stages
of intervention. The first phase will randomize parents and children to a parent education
condition, consisting of a parent support and education group focused on social communication
development, or to a parent mediated and therapist delivered condition involving coaching of
the parent with their child in social communication strategies. Phase 2 involves
re-randomizing parents and children to maintain the same treatment arm, or change to the
opposite arm to test the optimal sequence of intervention delivery and specific parent and
child characteristics that may moderate treatment success. In the final phase, dyads are
randomized to different maintenance arms, each comprised of 5 sessions with one involving
skype and text contact, the other in -home visits, to explore how best to maintain treatment
gains once the active intervention phase is complete. This study has the potential to
dramatically improve child social communication outcomes by individualizing and personalizing
parent intervention approaches with very young children, a high priority need of the
Interagency Autism Coordinating Council and NIH.
although to date studies yield inconsistent effects. One reason for the limited evidence may
be the considerable heterogeneity in both parent and child characteristics that affect the
fit of intervention to family and ultimately influence treatment outcome. For parents, these
factors might include stress associated with the uncertainty of their child's diagnosis,
caregiver expectations for the intervention itself, and a parent's own style of interaction
that may be influenced by milder but qualitatively similar ASD characteristics, known as the
broad autism phenotype (BAP). For children, these factors might include nonverbal DQ,
language, or sensory impairment. The fit between type of intervention and optimal outcome for
parent and child is an understudied, yet essential component of early intervention that may
be susceptible to the influence of heterogeneity in the parent and child. One approach to
addressing this variability is to implement an adaptive intervention approach that seeks to
capitalize on heterogeneity among children and parents. Utilizing an adaptive treatment
design, the current study tests the optimal sequence of intervention delivery and specific
parent and child characteristics that may moderate treatment success in three 10-week stages
of intervention. The first phase will randomize parents and children to a parent education
condition, consisting of a parent support and education group focused on social communication
development, or to a parent mediated and therapist delivered condition involving coaching of
the parent with their child in social communication strategies. Phase 2 involves
re-randomizing parents and children to maintain the same treatment arm, or change to the
opposite arm to test the optimal sequence of intervention delivery and specific parent and
child characteristics that may moderate treatment success. In the final phase, dyads are
randomized to different maintenance arms, each comprised of 5 sessions with one involving
skype and text contact, the other in -home visits, to explore how best to maintain treatment
gains once the active intervention phase is complete. This study has the potential to
dramatically improve child social communication outcomes by individualizing and personalizing
parent intervention approaches with very young children, a high priority need of the
Interagency Autism Coordinating Council and NIH.
While social communication is a core developmental deficit that characterizes children with
ASD, there is great heterogeneity in both presentation and gains with treatment. Long term
outcomes of children with ASD vary with nearly 40% remaining minimally verbal by school age.
Beginning early and providing high doses of intervention appears critical to child outcomes,
and one cost-effective, efficient way to accomplish these goals is to involve parents.
Particularly, for very young children (under the age of 3 years) who may not have a confirmed
ASD diagnosis, parent mediated interventions have several advantages. One is that there is
potential for earlier access to evidence based interventions. Parents can intervene with
their child immediately without waiting for access through a lengthy diagnostic process or
for therapist -delivered interventions that can have long wait times. Another is that parents
can increase the dose of an intervention since they are with their child for many more hours
than non-family members.
Despite the increasing numbers of parent mediated interventions, inconsistent results are
noted. A few studies have found significant differences in both child and parent outcomes but
others find limited to no effects on parent and/or child. This heterogeneity in outcomes is
often attributed to child characteristics or to the intervention itself. However, the fit
between type of intervention—focused on the parent—(education about social communication in
their child, or stress reduction interventions), or focused on the child—(parent coached to
work directly with their child)—has rarely been examined in parents engaged in these
interventions. Fit may be influenced by parent characteristics that can affect their ability
to implement the interventions.
These include stress associated with the uncertainty of their child's diagnosis, caregiver
expectations for the intervention itself, and parent's own style of interaction that may be
influenced by milder but qualitatively similar ASD characteristics, known as the broad autism
phenotype.
It is widely recognized that a single intervention is not effective for all parents and
children. One approach to addressing this variability is to implement an adaptive
intervention approach that seeks to capitalize on heterogeneity and evolving status among
children and parents. An adaptive intervention is a replicable, sequence of treatment
decision rules designed to help guide clinicians concerning whether, how or when—and based on
which measures—to provide certain intervention components. This type of intervention design
provides information on the most effective intervention for children and parents who need it
(leading to individualized and personalized sequences of treatment). Using a novel
experimental design, the proposed study will develop a more effective adaptive intervention
by addressing the following specific aims:
Primary Aim (Best Initial Strategy): To determine the effect of PARENT focused intervention
vs CHILD focused intervention on change in child initiated joint engagement (primary
outcome), play, and joint attention (secondary outcomes) from baseline to end of phase 1.
Hypothesis: Children will improve more, on average, when offered CHILD focused intervention.
Secondary Aim 1 (Best Sequence): To compare and contrast the four pre-specified adaptive
interventions from baseline to end of phase 2 on primary and secondary outcomes. Hypothesis:
The sequential intervention beginning with CHILD focused interventions followed by PARENT
education sessions will lead to the most improved outcomes.
Secondary Aim 2 (Toward More Personalized Intervention Sequences): To develop a more
individually- tailored adaptive intervention by examining whether parental factors including
BAP, parental stress, or parent's expectancies for the intervention, and child factors
including non-verbal DQ, language or sensory impairment at baseline moderates the effect of
Phase 1 interventions from baseline to end of Phase 1 on primary and secondary outcomes.
Hypotheses: (i) Children with parents who report greater BAP and parenting stress will
benefit more from PARENT focused intervention and children with parents who report greater
expectancy will benefit more from CHILD focused intervention. (ii) Children with low
non-verbal DQ and high levels of sensory impairment at baseline will benefit more from the
CHILD focused intervention from baseline to end of phase 1. Secondary Aim 3 (Maintenance
Protocol): To determine the maintenance effect of in person home visits versus technology
supported maintenance protocol on change in primary and secondary outcomes from (i) baseline
to end of phase 3 and (ii) from end of phase 2 to end of phase 3. Hypothesis: Children in the
home visit maintenance protocol will have more improved outcomes from baseline to end of
phase 3 compared to the children in the technology supported maintenance protocol.
Secondary Aim 4 (Exploratory: Biomarkers and Genetics): To characterize children at risk of
ASD in terms of electrophysiological biomarkers (neural synchrony measured by EEG power, peak
alpha frequency and coherence) and genetic risk (as measured by the presence of CNVs and
polygenetic risk score) and to explore each's role as a biological moderator of treatment
effects.
ASD, there is great heterogeneity in both presentation and gains with treatment. Long term
outcomes of children with ASD vary with nearly 40% remaining minimally verbal by school age.
Beginning early and providing high doses of intervention appears critical to child outcomes,
and one cost-effective, efficient way to accomplish these goals is to involve parents.
Particularly, for very young children (under the age of 3 years) who may not have a confirmed
ASD diagnosis, parent mediated interventions have several advantages. One is that there is
potential for earlier access to evidence based interventions. Parents can intervene with
their child immediately without waiting for access through a lengthy diagnostic process or
for therapist -delivered interventions that can have long wait times. Another is that parents
can increase the dose of an intervention since they are with their child for many more hours
than non-family members.
Despite the increasing numbers of parent mediated interventions, inconsistent results are
noted. A few studies have found significant differences in both child and parent outcomes but
others find limited to no effects on parent and/or child. This heterogeneity in outcomes is
often attributed to child characteristics or to the intervention itself. However, the fit
between type of intervention—focused on the parent—(education about social communication in
their child, or stress reduction interventions), or focused on the child—(parent coached to
work directly with their child)—has rarely been examined in parents engaged in these
interventions. Fit may be influenced by parent characteristics that can affect their ability
to implement the interventions.
These include stress associated with the uncertainty of their child's diagnosis, caregiver
expectations for the intervention itself, and parent's own style of interaction that may be
influenced by milder but qualitatively similar ASD characteristics, known as the broad autism
phenotype.
It is widely recognized that a single intervention is not effective for all parents and
children. One approach to addressing this variability is to implement an adaptive
intervention approach that seeks to capitalize on heterogeneity and evolving status among
children and parents. An adaptive intervention is a replicable, sequence of treatment
decision rules designed to help guide clinicians concerning whether, how or when—and based on
which measures—to provide certain intervention components. This type of intervention design
provides information on the most effective intervention for children and parents who need it
(leading to individualized and personalized sequences of treatment). Using a novel
experimental design, the proposed study will develop a more effective adaptive intervention
by addressing the following specific aims:
Primary Aim (Best Initial Strategy): To determine the effect of PARENT focused intervention
vs CHILD focused intervention on change in child initiated joint engagement (primary
outcome), play, and joint attention (secondary outcomes) from baseline to end of phase 1.
Hypothesis: Children will improve more, on average, when offered CHILD focused intervention.
Secondary Aim 1 (Best Sequence): To compare and contrast the four pre-specified adaptive
interventions from baseline to end of phase 2 on primary and secondary outcomes. Hypothesis:
The sequential intervention beginning with CHILD focused interventions followed by PARENT
education sessions will lead to the most improved outcomes.
Secondary Aim 2 (Toward More Personalized Intervention Sequences): To develop a more
individually- tailored adaptive intervention by examining whether parental factors including
BAP, parental stress, or parent's expectancies for the intervention, and child factors
including non-verbal DQ, language or sensory impairment at baseline moderates the effect of
Phase 1 interventions from baseline to end of Phase 1 on primary and secondary outcomes.
Hypotheses: (i) Children with parents who report greater BAP and parenting stress will
benefit more from PARENT focused intervention and children with parents who report greater
expectancy will benefit more from CHILD focused intervention. (ii) Children with low
non-verbal DQ and high levels of sensory impairment at baseline will benefit more from the
CHILD focused intervention from baseline to end of phase 1. Secondary Aim 3 (Maintenance
Protocol): To determine the maintenance effect of in person home visits versus technology
supported maintenance protocol on change in primary and secondary outcomes from (i) baseline
to end of phase 3 and (ii) from end of phase 2 to end of phase 3. Hypothesis: Children in the
home visit maintenance protocol will have more improved outcomes from baseline to end of
phase 3 compared to the children in the technology supported maintenance protocol.
Secondary Aim 4 (Exploratory: Biomarkers and Genetics): To characterize children at risk of
ASD in terms of electrophysiological biomarkers (neural synchrony measured by EEG power, peak
alpha frequency and coherence) and genetic risk (as measured by the presence of CNVs and
polygenetic risk score) and to explore each's role as a biological moderator of treatment
effects.
Inclusion Criteria:
- Have elevated scores on the ADOS-2 and clinical concern from a professional
(Pediatrician, Psychologist, etc.). For children under the age of 30 months, some of
whom may not have a diagnosis of ASD, they must show elevated risk in the
mild-to-moderate or moderate-to-severe risk categories on the ADOS-T. For children
over the age of 30 months, they must meet clinical cutoff on the ADOS-2, Module 1 or
2.
- Are between 12 months and 36 months
- Have a parent available for parent-mediated sessions 2 times per week in the
classroom
Exclusion Criteria:
- Do not have seizures or are stable on anti-seizure medication
- Do not have associated physical disorders
- Are not co-morbid with other syndromes or diseases unless they come from Project
I in our center— 22q11 deletion or TSC children at 12 months with concern for ASD
on the ADOS-T.
We found this trial at
1
site
Los Angeles, California 90095
Principal Investigator: Connie Kasari, PhD
Phone: 310-825-4775
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