Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05185128 |
| Other study ID # |
5200189 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2022 |
| Est. completion date |
April 2025 |
Study information
| Verified date |
April 2024 |
| Source |
Loma Linda University |
| Contact |
Aarti Nair, PhD |
| Phone |
9095588707 |
| Email |
anair[@]llu.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Difficulties in reciprocal social interaction are hallmark features of several
neuropsychiatric disorders, most notably autism spectrum disorder (ASD) and schizophrenia
spectrum disorder (SSD). While recent studies have demonstrated substantial overlap in
genetic etiology between ASD and SSD, little is known about common versus unique neural
mechanisms that may underlie these downstream social deficits that cross diagnostic
boundaries. Thus, a comprehensive imaging study examining social deficits in youth with ASD
and adolescent- onset SSD at the neurochemical, connectivity, as well as functional
activation level will be crucial in furthering our understanding of these underlying neural
mechanisms. Specifically, the current project aims to examine how targeted social skills
interventions may impact the organization of large-scale functional brain networks implicated
in social cognition in these disorders, leading to improved outcomes. Thirty adolescents with
ASD and 30 adolescents with SSD will undergo the Program for the Education and Enrichment of
Relational Skills (PEERS), which is a 16-week parent-assisted social skills intervention that
aims to improve friendship quality and social skills in teens with social difficulties. All
participants will receive pre- and post-treatment MRI scans including functional MRI and
magnetic resonance spectroscopy to quantify neural changes resulting from the intervention.
All participants will also receive behavioral and social cognition assessments pre- and
post-intervention to quantify real- world gains in social behaviors resulting from the
intervention. Additionally, 30 typically developing adolescents will be recruited to serve as
control participants and undergo two MRI and behavioral assessment sessions 16-weeks apart
with no intervention in between. Specific aims include (1) examining inter-group disruptions
in connectivity patterns, activation levels, and neurometabolite concentrations in key social
brain regions pre-treatment in ASD and SSD groups, (2) examining inter-group changes in
connectivity patterns, activation levels, and neurometabolite concentrations in key social
brain regions in response to treatment in ASD and SSD groups, and, (3) dimensionally
identifying intra-group differences in brain responses and how they relate to real-world
treatment outcomes.
Description:
Difficulties in reciprocal social interaction are hallmark features of several
neuropsychiatric disorders, most notably autism spectrum disorder (ASD) and schizophrenia
spectrum disorder (SSD). Recent behavioral studies of adults with SSD and ASD have
highlighted not only the similarities but also some divergent patterns of social impairments
in the two disorders - with ASD characterized by lower social motivation, poorer social
reciprocity, and undermentalizing, and SSD characterized by greater reciprocity but poor
expressiveness. Given the public health significance of social disability and social
isolation, it is crucial to explore the neurobiological mechanisms underlying these social
skill deficits across both groups, as well as to understand how these relate to real-world
behaviors. Although antipsychotics have been shown to be effective in reducing positive
symptoms in SSD, they are not effective in addressing the devastating social disability
associated with the disorder, which contributes to chronic functional impairment. It is thus
imperative to identify behavioral interventions for children and adolescents that have
already shown promise in other clinical groups such as ASD. By enhancing our understanding of
the neurobiological underpinnings of social impairments in adolescent-onset SSD and how they
compare to those observed in ASD, we will be able to refine treatment targets and better
predict outcomes for each group. To this effect, the proposed study will examine biomarkers
that are likely related to positive outcomes from targeted social skills intervention in
adolescents with SSD and ASD. Building upon an established evidence-based treatment - the
Program for the Education and Enrichment of Relational Skills (PEERS), we will collect
resting state functional imaging (rs-fcMRI), task-paradigm functional BOLD activation (fMRI),
and magnetic resonance spectroscopy (MRS) before and after 30 SSD and 30 ASD adolescents,
12-18 years of age, undergo the 16-week evidence-based PEERS behavioral intervention. These
data will then be compared to a matched sample of 30 typically developing (TD) adolescents
who are not enrolled in the PEERS program but will undergo two MRI scans 16-weeks apart. The
overarching goal of the study will be to create a novel multimodal neuroimaging design to
examine the neural underpinning of social difficulties in SSD and ASD, explore
neuroplasticity in both groups in response to a brief targeted social-skills intervention,
and predict treatment response and its contribution to long-term maintenance of skills after
treatment completion.
The following are the study's specific aims:
Aim 1: Assess treatment related changes in 'social brain' regions following evidence-based
social skills training in ASD and SSD group, compared to neural patterns observed in TD
adolescents.
Hypothesis 1a: rs-fcMRI indices within social brain networks will look more improved (similar
to TD adolescents) post-treatment compared to pre-treatment for the both ASD and SSD groups
(e.g., greater connectivity in social brain networks in ASD group, lower connectivity of
extraneous regions in SSD group).
Hypothesis 1b: fMRI brain activation in social brain regions in response to the social
task-paradigm will look more improved (similar to TD adolescents) post-treatment compared to
pre-treatment for both ASD and SSD group (e.g., greater activation in social brain networks
in ASD group, lower activation of extraneous regions in SSD group). Hypothesis 1c: There will
be significant improvement (similar to TD adolescents) in MRS indices of GABA (inhibitory)
and glutamate (excitatory) neurometabolite concentrations within social brain networks in ASD
and SSD post- treatment compared to pre-treatment (e.g., lower glutamate/higher GABA in
social brain regions in ASD group, higher glutamate/higher GABA in social brain regions in
SSD group).
Aim 2: To test whether pre- and post-treatment neural changes are meaningfully related to
behavioral measures of treatment outcome.
Hypothesis 2: Neural responses post-intervention will correlate with gains in social
motivation and reciprocity behavioral outcomes measures in the ASD group, and gains in social
expressivity outcome measures in the SSD group.
Exploratory Aim 3: Given that both ASD and SSD are characterized as spectrum disorders of
varying severity, heterogeneous etiologies, and comorbidities, we aim to explore how
individual differences in patterns of brain connectivity and activation might predict
treatment response and treatment maintenance dimensionally in addition to the category-based
diagnostic systems proposed above. Given the exploratory nature of the proposed aim, specific
hypotheses are not projected regarding the precise changes in neural activity on an
individual basis. However, accomplishing this goal will us understand underlying neural
mechanisms of treatment-related change across groups, and serve to better target
interventions to address the heterogeneity of social cognition deficits observed in both ASD
and SSD.
