Autism Spectrum DisorderNCT03199937
Executive Function Intervention for High School Students With ASD
A study testing Flexible Futures in people with Autism Spectrum Disorder, run by Children's National Research Institute at 1 site in United States.
Trial summary
The purpose of this project is to test the effectiveness of a novel school-based intervention targeting executive function skills, including flexibility and planning, in college-track, transition-age youth with ASD. Read more about this study
- Who is it for?
- Ages 14 to 22 years
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- Flexible Futures
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jul 2015to 30 Jun 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- College-track high school students
- Ages 14-22
- Verbal IQ estimate of ≥ 90 on the Wechsler Abbreviated Intelligence Scale-2
- Clinical diagnosis of ASD OR school classification of autism confirmed by clinical impressions and the Social Responsiveness Scale-Revised total score ≥ 65. If the research staff feels that clinical impressions indicate a diagnosis, but parent report is below threshold, the Autism Diagnostic Observation Schedule-2 will be completed.
Who cannot join
- Bipolar disorder, schizophrenia, or major depression that is currently preventing from participation in classroom activities
- MRI exclusion: contraindication (metal implant or medical device) for MRI
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Research Institute
Washington D.C., District of Columbia, 20010
About this study
Official title: Behavioral and Neural Outcomes of a New Executive Function Treatment for Transition-age Youth With ASD
The purpose of this project is to test the effectiveness of a novel school-based intervention targeting executive function skills, including flexibility and planning, in college-track, transition-age youth with ASD. Evaluating treatment change through behavior and brain activity provides important information on how the treatment works and who will best benefit from it.
Read the detailed description
With half of the $3.2 million lifetime per capita cost of autism spectrum disorder (ASD) attributable to care and productivity loss during adult life, the Interagency Autism Coordinating Committee has identified a pressing need to improve adult outcomes. Even in individuals without intellectual disability who make up 2/3 of children with ASD, as few as 9% reach full functional independence as adults. Failure in college is related to weaknesses in executive function (EF), specifically with flexibility and planning. As such, the transition from high school is a period of amplified risk characterized by poor educational and vocational attainment that persists in adulthood. EF problems are pivotal targets for intervention because they are common, linked to independence, and responsive to treatment in younger children. There are three barriers to treatment outcome research in transition-aged youth with ASD: (1) a lack of proven EF treatments for this age, (2) pervasive failure to generalize skills learned in the clinic to real-world settings, and (3) inadequate objective measures of outcome. This proposal tests the effectiveness of Flexible Futures a new phenotype specific, cognitive behavioral EF intervention to increase flexibility and planning skills for college-track high school students with ASD. It is novel and innovative because its use of translational methods comprehensively evaluates treatment change at the behavioral, cognitive, and neural level.
Cognitive flexibility and planning are impaired in ASD, linked to core ASD symptoms, and embedded in anomalies of brain structure and function. Individuals with ASD fail to activate local cortical regions such as dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) on set-shifting (flexibility) tasks and show global abnormalities in the default mode, salience, and attentional networks associated with EF problems in attending to important information and implementing goal-directed behavior. In typical development, greater segregation between and greater connectivity within these networks is associated with better cognitive and behavioral regulation. Dr. Pugliese aims to determine whether treatment change can be objectively measured in the brain using functional MRI (fMRI). This cutting edge methodology is critical to identifying processes of treatment change at the neural level, consistent with the NIMH Research Domain Criteria framework, and may yield findings that impact the large variety of psychiatric and developmental disorders linked to EF deficits. Specifically, this study aligns with NIMH K23 guidance soliciting proposals for the development of pilot studies of novel treatments eliciting mechanisms of change.
AIM 1: Refine the Flexible Futures treatment manual and test acceptability, feasibility, and effectiveness in a school setting.
Dr. Pugliese will refine the Flexible Futures manual based on expert opinion and feedback from our in-clinic pilot via an iterative process and run a school-based trial comparing Flexible Futures to social skills treatment. It is hypothesized that intervention acceptability, feasibility, and fidelity will reach an 80% benchmark (H1.1) and students who receive Flexible Futures will show improved EF flexibility and planning abilities in laboratory, school, and home settings post-treatment and at 5-month follow up compared to students who receive treatment as usual (H1.2).
AIM 2: Identify neural correlates of treatment change using fMRI.
Task-evoked and resting-state activation of prefrontal cortex networks will be assessed pre-/post-intervention. It is hypothesized that post-treatment, students receiving Flexible Futures will display increased (normalized) DLPFC and ACC activation during a well-established set-shifting task compared to those receiving social skills training (H2.1), and that activation will be positively correlated with behavioral/cognitive measures of EF (H2.2). It is also hypothesized that post-treatment, students receiving Flexible Futures will display increased connectivity within, and decreased connectivity across default mode, salience, and attentional networks compared to the control group (H2.3).
AIM 3: Identify biomarkers of later EF outcomes at the behavioral, cognitive, and neural level.
Baseline data will be combined across participants to provide a comprehensive EF profile in transition-age youth and identify predictors of later EF and global outcomes. It is hypothesized that baseline measures of EF (behavioral/ cognitive); DLPFC/ACC activation; and greater connectivity within and greater segregation between salience, attentional and default mode networks (neural) will all predict EF outcome and adaptive function. (H3.1).
Significance: Establishing the first effective school-based EF treatment for high-schoolers will provide critical and generalizable transition-related support, and a model for treatment in other prevalent disorders with known EF deficits (e.g. ADHD, anxiety). This training award will launch me toward Dr. Pugliese's ultimate career goals of 1) developing and implementing innovative interventions personalized for specific cognitive profiles, 2) developing school-based treatments to overcome disparities in access to healthcare; and 3) utilizing treatment studies as vehicles to identify biomarkers and provide insight into neural correlates of treatment change.
- Conditions
- Autism Spectrum Disorder
- Being tested
- Flexible Futures, Current standard of care
- Keywords
- Autism Spectrum Disorder, Executive Functioning, Intervention, Flexible, Unstuck, Transition, Behavior, High school, Problem Solving, Self-Control, Coping
- Medical subject headings
- Autism Spectrum Disorder, Behavior, Self-Control
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flexible FuturesBehavioural
Flexible Futures is a novel and innovative cognitive-behavioral treatment that directly addresses executive function and self-regulation deficits in ASD. Flexible futures targets flexibility and planning through self-regulatory scripts that are consistently modeled and reinforced. Scripts compensate for the inner speech and organization/integration deficits in ASD, and are practiced repeatedly to achieve automaticity. Content focuses on key functions needed for college success, such as: intrinsic motivation, how to implement skills socially, self-advocacy skills application of flexibility and organization scripts and strategies in the service of a long-term goal, and management of time and priorities.
Current standard of careOther
Flexible Futures will be compared to a social skills treatment as usual that capitalizes on current standard of care provided by local school districts.
| Study group | Role | What they receive |
|---|---|---|
| Flexible Futures | Experimental | Flexible Futures uses cognitive behavioral therapy (CBT) techniques to target flexibility and planning by teaching core skills through personal goals chosen by students during treatment. Flexible Futures focuses on key functions needed for college success, such as: intrinsic motivation, how to implement skills socially, how thoughts and feelings affect planning and flexibility, self-advocacy skills necessary to promote independence, application of flexibility and organization scripts and strategies in the service of a long-term goal, and management of time and priorities. Guided practice begins with concrete interventionist support, and moves to interventionist cueing, self-cueing, and finally automatic use of the skills without support. Generalization is maximized with school staff as interventionists, parent training, home and classroom extension activities, and role-playing use of strategies in novel situations. Motivation is developed using student choice and natural motivators. Receives: Behavioral: Flexible Futures |
| Waitlist control group | Active comparator | Current standard of care Receives: Other: Current standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Behavior Rating Inventory of Executive Function (BRIEF)- Self-Report Form (Gioia, Isquith, Guy & Kenworthy, 2000).
This self-report measure has 55 items with seven clinical scales and three validity scales. It is normed for adolescents between 11 and 18 years of age. Items were developed to capture everyday behaviors associated with EF and tap seven domains: Inhibit, Self-Monitor, shift, Emotional Control, Task Completion, Working Memory, and Plan/Organize. The BRIEF is standardized with normative data expressed as T scores (mean=50; SD=10). Internal consistency is high, with index coefficients in the mid .90s to high .90s, while test-retest stability coefficients for the clinical scales ranged from .67-.79 within the standardization subsample. The individual scales and summary indexes were correlated in various clinical samples with other measures of attentional and behavioral functioning (Behavior Assessment Scales for Children, Child Behavior Checklist, ADHD-RS-IV, Conners 3), providing evidence of convergent and divergent validity.
Safety Issue: No
Measured: On average, 8 and 13 months
Change in Challenge Task (CT) scores
The Challenge Task is an unpublished, un-normed measure designed by the study staff to measure flexibility and planning in a social context with standardized tasks (Anthony \& Kenworthy, 2012). It is a 20-minute play interview that challenges children to be flexible and planful in the context of three activities with an examiner. Specific challenges are posed, and the child's flexibility and planning are scored on a 3-point scale for each task. The scale has task-specific behavioral markers to guide. The CT yields average Flexibility and Planning scores (higher scores indicate greater impairment). Reliability observations will be completed with a second coder for 25% of the videotapes. Examiners in a previous trial achieved interrater agreement >90%, and we will maintain that same standard for the current project.
Safety Issue: No
Measured: On average, 8 and 13 months
Change in Wechsler Abbreviated Scale of Intelligence- Second Edition (WASI-II, Wechsler, 2011), block design subtest
The WASI-II is an estimate of intelligence, comprised of four subtests, which takes 30-45 minutes to administer. It is a well-standardized task with normative data for ages 6-90. Subtests include the Block Design subtest, the Similarities subtest, the Matrix Reasoning subtest, and the Vocabulary subtest. Performance on each subtest is represented as a T score (mean=50; SD=10), with higher scores indicating better performance. Overall IQ is calculated from a composite of all four subtests and is represented as a standard score (mean=100; SD=15). The entire WASI-2 will be completed at the Baseline Evaluation to identify full-scale IQ and verbal age (based on the vocabulary subtest). Subsequently, the Block Design subtest only will be completed at the Post-Treatment and Long-term Follow-up Evaluations.
Safety Issue: No
Measured: On average, 8 and 13 months
Change in Delis-Kaplan Executive Functioning System (DKEFS; Delis, Kaplan, and Kramer, 2001), Sorting subtest
The DKEFS is a standardized measure of executive functioning skills and in normed for ages eight through adulthood. The Sorting Subtest particularly measures flexibility. The DKEFS will be completed both at the Baseline and, the Post-Intervention Evaluation as measure of outcome. It takes approximately 10 minutes to administer, and although specific data were not available, the measure has been well documented across several neuropsychological studies to have evidence of reliability and validity.
Safety Issue: No
Measured: On average, 8 and 13 months
Change in Tower of London-Drexel (TOL-DX; Culbertson & Zillmer, 2000) scores
TOL-DX measures multiple EFs such as planning, inhibition, and working memory. It requires the subject to work step-by-step to copy a pattern of beads on pegs using the least number of moves possible. The total-moves score will be measured as an omnibus measure of EF. Results are reported as standard scores (M = 100; SD = 15).
Safety Issue: No
Measured: On average, 8 and 13 months
Change in Adaptive Behavior Assessment System-Second Edition (ABAS-2)
(ABAS-II; Harrison and Oakland 2003) is a measure of adaptive behavior with national standardization samples representative of the English speaking US population. The informant report adult form of the ABAS-2(Harrison and Oakland 2003) used in the present study was standardized on an age stratified sample and provided information in the areas of Conceptual (including Communication, Functional Academics, Self-Direction), Social (including not only Social but also Leisure), and Practical (including Community Use, Home Living, Health and Safety, Self-Care) Skills, all of which are presented as norm-referenced standard scores (M = 100; SD = 15) and were used as correlates of interest in the present study.
Safety Issue: No
Measured: On average, 8 and 13 months
Social Responsiveness Scale-Second Edition (SRS-2; Constantino and Gruber 2012)
The SRS-2 is a 65-item informant report of autistic traits rated on a 4-point Likert Scale (0-3 points). Higher scores indicate more autistic traits; T-scores ≥ 65 (i.e., 1.5 SDs ≥ the population mean of 50) suggest clinically significant autistic traits. The SRS-2 scoring is aligned with DSM-5 criteria for diagnosis of an ASD. The update includes the creation of two higher order indices that correspond to the two symptom domains of ASD: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB). Informants provided a single SRS-2 rating for each child in this study. The SRS-2 will be completed at Baseline and Post-Intervention testing.
Safety Issue: No
Measured: On average, 8 and 13 months
Change in Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2)- Parent Form (Gioia, Isquith, Guy & Kenworthy, 2015).
This parent-report measure contains 63 items with nine clinical scales and three validity scales. It is normed for children ages 5-18. Items were developed to capture everyday behaviors associated with EF and tap nine domains including: Inhibit, Self-Monitor, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, Task-Monitor, and Organization of Materials. It is a standardized questionnaire with normative data and standardized scores expressed as T scores (mean=50; SD=10). Internal consistency is high, with index coefficients above .90, while test-retest stability coefficients for the clinical scales ranged from .67-.92 within the parent standardization subsample. The individual scales and summary indexes of the BRIEF-2 were correlated in various clinical samples with other measures of attentional and behavioral functioning (BASC, CBCL, ADHD-RS-IV, Conners 3), which collectively provided evidence of convergent and divergent validity. Safety Issue: No
Measured: On average, 8 and 13 months
Flexibility and Planning Interference Scale
To meet the needs of the current study by addressing the issue of flexibility more specifically, we will modify the BRIEF to include 14 additional unpublished, unnormed "Flexibility" and "Interference" items. These items will assess how much flexibility impacts the child's and family's life. The items will use a 0-3 scale (0-No Interference, 1-Mildly interfering , 2-Moderately Interfering, 3- Severely Interfering) and will ask about behavior observed during the past two weeks (example: "How much do difficulties with flexibility interfere with or disrupt everyday activities (self-care, school, etc.?)") Safety Issue: No
Measured: On average, 8 and 13 months
The Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP, Swanson, 1992)
The SKAMP is a teacher rating scale that takes 5 minutes to complete and assesses impairment from classroom behaviors associated with executive function in adolescents. Although our study uses a modified form of the SKAMP for which reliability and validity data are unavailable, previous community-based trials of the SKAMP showed evidence of high internal consistency, with reliabilities of .98 for overall SKAMP scores, .96 for Deportment (Behavior), and .95 for Attention. The SKAMP was found to be strongly correlated to both parent and teacher versions of the Swanson, Nolan, and Pelham-IV (SNAP-IV; r = .93 and .79 for Inattention and Hyperactivity/Impulsivity). Teachers rate the severity of 10 common behaviors on a 4-point scale, including 6 items related to attention and 4 items related to problematic behavior.
Safety Issue: No
Measured: On average, 8 and 13 months
Classroom Observations
To further assess functional improvement, at least two 15-minute classroom observations will be conducted by an intervention-blind research assistant (who has achieved reliability on coding criteria) for every study participant. They will occur randomly during the academic school day, but not during Flexible Futures small group sessions or Social Skills training. The following behaviors will be coded for children in this study: Reciprocity, Following Rules, Transitions, Gets Stuck, Negativity/Overwhelm, and Classroom Participation. During the classroom observations, the following behaviors will be coded for the teacher's behavior: Flexibility, Planning/Organizing, Provides Clear Instructions/ Expectations, Actively Uses Visual Support, References Classroom Rules, Maintains Positive Praise: Command/Correction ratio and Uses Reward System.
Safety Issue: No
Measured: On average, 8 and 13 months
Cognitive Flexibility Task
A task-based fMRI procedure will be used to detect pre-to-post treatment change. Participants will classify pairs of stimuli (objects and pictures) on the basis of how well they "go together" and respond with an appropriate button press. The specific task may change based on pilot results but will be similar to what is proposed.
Safety Issue: No
Measured: On average, 8 and 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2017
- Study start11 Jul 2015
- Primary completion23 Apr 2019
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (71)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's National Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Georgetown University
- Responsible party
- Principal investigator, Cara Pugliese, Children's National Research Institute
- Investigators
- Cara E Pugliese, Ph.D., Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03199937
- Sponsor's protocol ID
- 1K23MH110612-01
- Other IDs
- OAR Innovative Research Award
- Status last verified
- Apr 2020
- First submitted
- 21 Jun 2017
- Last updated
- 10 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pugliese CE, White SW. Brief report: problem solving therapy in college students with autism spectrum disorders: feasibility and preliminary efficacy. J Autism Dev Disord. 2014 Mar;44(3):719-29. doi: 10.1007/s10803-013-1914-8.
PubMed 23963592Pennington BF, Ozonoff S. Executive functions and developmental psychopathology. J Child Psychol Psychiatry. 1996 Jan;37(1):51-87. doi: 10.1111/j.1469-7610.1996.tb01380.x.
PubMed 8655658Frith U. Why we need cognitive explanations of autism. Q J Exp Psychol (Hove). 2012;65(11):2073-92. doi: 10.1080/17470218.2012.697178. Epub 2012 Aug 21.
PubMed 22906000Ganz ML. The lifetime distribution of the incremental societal costs of autism. Arch Pediatr Adolesc Med. 2007 Apr;161(4):343-9. doi: 10.1001/archpedi.161.4.343.
PubMed 17404130Interagency Autism Coordinating Committee. The 2011 Interagency Autism Coordinating Committee Strategic Plan for Autism Spectrum Disorder Research.; 2011.
Farley MA, McMahon WM, Fombonne E, Jenson WR, Miller J, Gardner M, Block H, Pingree CB, Ritvo ER, Ritvo RA, Coon H. Twenty-year outcome for individuals with autism and average or near-average cognitive abilities. Autism Res. 2009 Apr;2(2):109-18. doi: 10.1002/aur.69.
PubMed 19455645Gobbo K, Shmulsky S. Faculty Experience With College Students With Autism Spectrum Disorders: A Qualitative Study of Challenges and Solutions. Focus Autism Other Dev Disabl. 2013;29(1):13-22. doi:10.1177/1088357613504989.
Taylor JL, Mailick MR. A longitudinal examination of 10-year change in vocational and educational activities for adults with autism spectrum disorders. Dev Psychol. 2014 Mar;50(3):699-708. doi: 10.1037/a0034297. Epub 2013 Sep 2.
PubMed 24001150Hume K, Loftin R, Lantz J. Increasing independence in autism spectrum disorders: a review of three focused interventions. J Autism Dev Disord. 2009 Sep;39(9):1329-38. doi: 10.1007/s10803-009-0751-2. Epub 2009 May 9.
PubMed 19430897Hill EL. Executive dysfunction in autism. Trends Cogn Sci. 2004 Jan;8(1):26-32. doi: 10.1016/j.tics.2003.11.003.
PubMed 14697400Pugliese CE, Anthony L, Strang JF, Dudley K, Wallace GL, Kenworthy L. Increasing adaptive behavior skill deficits from childhood to adolescence in autism spectrum disorder: role of executive function. J Autism Dev Disord. 2015 Jun;45(6):1579-87. doi: 10.1007/s10803-014-2309-1.
PubMed 25398602Kenworthy L, Anthony LG, Naiman DQ, Cannon L, Wills MC, Luong-Tran C, Werner MA, Alexander KC, Strang J, Bal E, Sokoloff JL, Wallace GL. Randomized controlled effectiveness trial of executive function intervention for children on the autism spectrum. J Child Psychol Psychiatry. 2014 Apr;55(4):374-83. doi: 10.1111/jcpp.12161. Epub 2013 Nov 21.
PubMed 24256459Taylor JL, Dove D, Veenstra-VanderWeele J, et al. Comparative Effictiveness Review: Interventions for Adolescents and Young Adults With Autism. 2012;(65).
Dingfelder HE, Mandell DS. Bridging the research-to-practice gap in autism intervention: an application of diffusion of innovation theory. J Autism Dev Disord. 2011 May;41(5):597-609. doi: 10.1007/s10803-010-1081-0.
PubMed 20717714Kenworthy L, Black DO, Harrison B, della Rosa A, Wallace GL. Are executive control functions related to autism symptoms in high-functioning children? Child Neuropsychol. 2009 Sep;15(5):425-40. doi: 10.1080/09297040802646983.
PubMed 19173090
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Behavioral and Neural Outcomes of a New Executive Function Treatment for Transition-age Youth With ASD
- ClinicalTrials.gov ID
- NCT03199937
- Acronym / sponsor ID
- 1K23MH110612-01
- Conditions
- Autism Spectrum Disorder
- Keywords
- Autism Spectrum Disorder, Executive Functioning, Intervention, Flexible, Unstuck, Transition, Behavior, High school
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Children's National Research InstituteUniversity, hospital or other
- Collaborators
- Georgetown University
- Study start
- 11 Jul 2015 (actual)
- Primary completion
- 23 Apr 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 27 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this project is to test the effectiveness of a novel school-based intervention targeting executive function skills, including flexibility and planning, in college-track, transition-age youth with ASD. Evaluating treatment change through behavior and brain activity provides important information on how the treatment works and who will best benefit from it.
Detailed description
With half of the $3.2 million lifetime per capita cost of autism spectrum disorder (ASD) attributable to care and productivity loss during adult life, the Interagency Autism Coordinating Committee has identified a pressing need to improve adult outcomes. Even in individuals without intellectual disability who make up 2/3 of children with ASD, as few as 9% reach full functional independence as adults. Failure in college is related to weaknesses in executive function (EF), specifically with flexibility and planning. As such, the transition from high school is a period of amplified risk characterized by poor educational and vocational attainment that persists in adulthood. EF problems are pivotal targets for intervention because they are common, linked to independence, and responsive to treatment in younger children. There are three barriers to treatment outcome research in transition-aged youth with ASD: (1) a lack of proven EF treatments for this age, (2) pervasive failure to generalize skills learned in the clinic to real-world settings, and (3) inadequate objective measures of outcome. This proposal tests the effectiveness of Flexible Futures a new phenotype specific, cognitive behavioral EF intervention to increase flexibility and planning skills for college-track high school students with ASD. It is novel and innovative because its use of translational methods comprehensively evaluates treatment change at the behavioral, cognitive, and neural level.
Cognitive flexibility and planning are impaired in ASD, linked to core ASD symptoms, and embedded in anomalies of brain structure and function. Individuals with ASD fail to activate local cortical regions such as dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) on set-shifting (flexibility) tasks and show global abnormalities in the default mode, salience, and attentional networks associated with EF problems in attending to important information and implementing goal-directed behavior. In typical development, greater segregation between and greater connectivity within these networks is associated with better cognitive and behavioral regulation. Dr. Pugliese aims to determine whether treatment change can be objectively measured in the brain using functional MRI (fMRI). This cutting edge methodology is critical to identifying processes of treatment change at the neural level, consistent with the NIMH Research Domain Criteria framework, and may yield findings that impact the large variety of psychiatric and developmental disorders linked to EF deficits. Specifically, this study aligns with NIMH K23 guidance soliciting proposals for the development of pilot studies of novel treatments eliciting mechanisms of change.
AIM 1: Refine the Flexible Futures treatment manual and test acceptability, feasibility, and effectiveness in a school setting.
Dr. Pugliese will refine the Flexible Futures manual based on expert opinion and feedback from our in-clinic pilot via an iterative process and run a school-based trial comparing Flexible Futures to social skills treatment. It is hypothesized that intervention acceptability, feasibility, and fidelity will reach an 80% benchmark (H1.1) and students who receive Flexible Futures will show improved EF flexibility and planning abilities in laboratory, school, and home settings post-treatment and at 5-month follow up compared to students who receive treatment as usual (H1.2).
AIM 2: Identify neural correlates of treatment change using fMRI.
Task-evoked and resting-state activation of prefrontal cortex networks will be assessed pre-/post-intervention. It is hypothesized that post-treatment, students receiving Flexible Futures will display increased (normalized) DLPFC and ACC activation during a well-established set-shifting task compared to those receiving social skills training (H2.1), and that activation will be positively correlated with behavioral/cognitive measures of EF (H2.2). It is also hypothesized that post-treatment, students receiving Flexible Futures will display increased connectivity within, and decreased connectivity across default mode, salience, and attentional networks compared to the control group (H2.3).
AIM 3: Identify biomarkers of later EF outcomes at the behavioral, cognitive, and neural level.
Baseline data will be combined across participants to provide a comprehensive EF profile in transition-age youth and identify predictors of later EF and global outcomes. It is hypothesized that baseline measures of EF (behavioral/ cognitive); DLPFC/ACC activation; and greater connectivity within and greater segregation between salience, attentional and default mode networks (neural) will all predict EF outcome and adaptive function. (H3.1).
Significance: Establishing the first effective school-based EF treatment for high-schoolers will provide critical and generalizable transition-related support, and a model for treatment in other prevalent disorders with known EF deficits (e.g. ADHD, anxiety). This training award will launch me toward Dr. Pugliese's ultimate career goals of 1) developing and implementing innovative interventions personalized for specific cognitive profiles, 2) developing school-based treatments to overcome disparities in access to healthcare; and 3) utilizing treatment studies as vehicles to identify biomarkers and provide insight into neural correlates of treatment change.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Flexible Futures | Experimental | Behavioral: Flexible FuturesFlexible Futures uses cognitive behavioral therapy (CBT) techniques to target flexibility and planning by teaching core skills through personal goals chosen by students during treatment. Flexible Futures focuses on key functions needed for college success, such as: intrinsic motivation, how to implement skills socially, how thoughts and feelings affect planning and flexibility, self-advocacy skills necessary to promote independence, application of flexibility and organization scripts and strategies in the service of a long-term goal, and management of time and priorities. Guided practice begins with concrete interventionist support, and moves to interventionist cueing, self-cueing, and finally automatic use of the skills without support. Generalization is maximized with school staff as interventionists, parent training, home and classroom extension activities, and role-playing use of strategies in novel situations. Motivation is developed using student choice and natural motivators. |
| Waitlist control group | Active comparator | Other: Current standard of careCurrent standard of care |
Who may qualify
- Ages
- 14 to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- College-track high school students
- Ages 14-22
- Verbal IQ estimate of ≥ 90 on the Wechsler Abbreviated Intelligence Scale-2
- Clinical diagnosis of ASD OR school classification of autism confirmed by clinical impressions and the Social Responsiveness Scale-Revised total score ≥ 65. If the research staff feels that clinical impressions indicate a diagnosis, but parent report is below threshold, the Autism Diagnostic Observation Schedule-2 will be completed.
Key exclusion criteria (2 listed)
- Bipolar disorder, schizophrenia, or major depression that is currently preventing from participation in classroom activities
- MRI exclusion: contraindication (metal implant or medical device) for MRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Flexible FuturesFlexible Futures is a novel and innovative cognitive-behavioral treatment that directly addresses executive function and self-regulation deficits in ASD. Flexible futures targets flexibility and planning through self-regulatory scripts that are consistently modeled and reinforced. Scripts compensate for the inner speech and organization/integration deficits in ASD, and are practiced repeatedly to achieve automaticity. Content focuses on key functions needed for college success, such as: intrinsic motivation, how to implement skills socially, self-advocacy skills application of flexibility and organization scripts and strategies in the service of a long-term goal, and management of time and priorities. | Behavioural | Flexible Futures |
| Current standard of careFlexible Futures will be compared to a social skills treatment as usual that capitalizes on current standard of care provided by local school districts. | Other | Waitlist control group |
Primary outcome
Change in Behavior Rating Inventory of Executive Function (BRIEF)- Self-Report Form (Gioia, Isquith, Guy & Kenworthy, 2000).
Time frame: On average, 8 and 13 months
This self-report measure has 55 items with seven clinical scales and three validity scales. It is normed for adolescents between 11 and 18 years of age. Items were developed to capture everyday behaviors associated with EF and tap seven domains: Inhibit, Self-Monitor, shift, Emotional Control, Task Completion, Working Memory, and Plan/Organize. The BRIEF is standardized with normative data expressed as T scores (mean=50; SD=10). Internal consistency is high, with index coefficients in the mid .90s to high .90s, while test-retest stability coefficients for the clinical scales ranged from .67-.79 within the standardization subsample. The individual scales and summary indexes were correlated in various clinical samples with other measures of attentional and behavioral functioning (Behavior Assessment Scales for Children, Child Behavior Checklist, ADHD-RS-IV, Conners 3), providing evidence of convergent and divergent validity. Safety Issue: No
Change in Challenge Task (CT) scores
Time frame: On average, 8 and 13 months
The Challenge Task is an unpublished, un-normed measure designed by the study staff to measure flexibility and planning in a social context with standardized tasks (Anthony \& Kenworthy, 2012). It is a 20-minute play interview that challenges children to be flexible and planful in the context of three activities with an examiner. Specific challenges are posed, and the child's flexibility and planning are scored on a 3-point scale for each task. The scale has task-specific behavioral markers to guide. The CT yields average Flexibility and Planning scores (higher scores indicate greater impairment). Reliability observations will be completed with a second coder for 25% of the videotapes. Examiners in a previous trial achieved interrater agreement >90%, and we will maintain that same standard for the current project. Safety Issue: No
Change in Wechsler Abbreviated Scale of Intelligence- Second Edition (WASI-II, Wechsler, 2011), block design subtest
Time frame: On average, 8 and 13 months
The WASI-II is an estimate of intelligence, comprised of four subtests, which takes 30-45 minutes to administer. It is a well-standardized task with normative data for ages 6-90. Subtests include the Block Design subtest, the Similarities subtest, the Matrix Reasoning subtest, and the Vocabulary subtest. Performance on each subtest is represented as a T score (mean=50; SD=10), with higher scores indicating better performance. Overall IQ is calculated from a composite of all four subtests and is represented as a standard score (mean=100; SD=15). The entire WASI-2 will be completed at the Baseline Evaluation to identify full-scale IQ and verbal age (based on the vocabulary subtest). Subsequently, the Block Design subtest only will be completed at the Post-Treatment and Long-term Follow-up Evaluations. Safety Issue: No
Change in Delis-Kaplan Executive Functioning System (DKEFS; Delis, Kaplan, and Kramer, 2001), Sorting subtest
Time frame: On average, 8 and 13 months
The DKEFS is a standardized measure of executive functioning skills and in normed for ages eight through adulthood. The Sorting Subtest particularly measures flexibility. The DKEFS will be completed both at the Baseline and, the Post-Intervention Evaluation as measure of outcome. It takes approximately 10 minutes to administer, and although specific data were not available, the measure has been well documented across several neuropsychological studies to have evidence of reliability and validity. Safety Issue: No
Change in Tower of London-Drexel (TOL-DX; Culbertson & Zillmer, 2000) scores
Time frame: On average, 8 and 13 months
TOL-DX measures multiple EFs such as planning, inhibition, and working memory. It requires the subject to work step-by-step to copy a pattern of beads on pegs using the least number of moves possible. The total-moves score will be measured as an omnibus measure of EF. Results are reported as standard scores (M = 100; SD = 15). Safety Issue: No
Change in Adaptive Behavior Assessment System-Second Edition (ABAS-2)
Time frame: On average, 8 and 13 months
(ABAS-II; Harrison and Oakland 2003) is a measure of adaptive behavior with national standardization samples representative of the English speaking US population. The informant report adult form of the ABAS-2(Harrison and Oakland 2003) used in the present study was standardized on an age stratified sample and provided information in the areas of Conceptual (including Communication, Functional Academics, Self-Direction), Social (including not only Social but also Leisure), and Practical (including Community Use, Home Living, Health and Safety, Self-Care) Skills, all of which are presented as norm-referenced standard scores (M = 100; SD = 15) and were used as correlates of interest in the present study. Safety Issue: No
Social Responsiveness Scale-Second Edition (SRS-2; Constantino and Gruber 2012)
Time frame: On average, 8 and 13 months
The SRS-2 is a 65-item informant report of autistic traits rated on a 4-point Likert Scale (0-3 points). Higher scores indicate more autistic traits; T-scores ≥ 65 (i.e., 1.5 SDs ≥ the population mean of 50) suggest clinically significant autistic traits. The SRS-2 scoring is aligned with DSM-5 criteria for diagnosis of an ASD. The update includes the creation of two higher order indices that correspond to the two symptom domains of ASD: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB). Informants provided a single SRS-2 rating for each child in this study. The SRS-2 will be completed at Baseline and Post-Intervention testing. Safety Issue: No
Change in Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2)- Parent Form (Gioia, Isquith, Guy & Kenworthy, 2015).
Time frame: On average, 8 and 13 months
This parent-report measure contains 63 items with nine clinical scales and three validity scales. It is normed for children ages 5-18. Items were developed to capture everyday behaviors associated with EF and tap nine domains including: Inhibit, Self-Monitor, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, Task-Monitor, and Organization of Materials. It is a standardized questionnaire with normative data and standardized scores expressed as T scores (mean=50; SD=10). Internal consistency is high, with index coefficients above .90, while test-retest stability coefficients for the clinical scales ranged from .67-.92 within the parent standardization subsample. The individual scales and summary indexes of the BRIEF-2 were correlated in various clinical samples with other measures of attentional and behavioral functioning (BASC, CBCL, ADHD-RS-IV, Conners 3), which collectively provided evidence of convergent and divergent validity. Safety Issue: No
Flexibility and Planning Interference Scale
Time frame: On average, 8 and 13 months
To meet the needs of the current study by addressing the issue of flexibility more specifically, we will modify the BRIEF to include 14 additional unpublished, unnormed "Flexibility" and "Interference" items. These items will assess how much flexibility impacts the child's and family's life. The items will use a 0-3 scale (0-No Interference, 1-Mildly interfering , 2-Moderately Interfering, 3- Severely Interfering) and will ask about behavior observed during the past two weeks (example: "How much do difficulties with flexibility interfere with or disrupt everyday activities (self-care, school, etc.?)") Safety Issue: No
The Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP, Swanson, 1992)
Time frame: On average, 8 and 13 months
The SKAMP is a teacher rating scale that takes 5 minutes to complete and assesses impairment from classroom behaviors associated with executive function in adolescents. Although our study uses a modified form of the SKAMP for which reliability and validity data are unavailable, previous community-based trials of the SKAMP showed evidence of high internal consistency, with reliabilities of .98 for overall SKAMP scores, .96 for Deportment (Behavior), and .95 for Attention. The SKAMP was found to be strongly correlated to both parent and teacher versions of the Swanson, Nolan, and Pelham-IV (SNAP-IV; r = .93 and .79 for Inattention and Hyperactivity/Impulsivity). Teachers rate the severity of 10 common behaviors on a 4-point scale, including 6 items related to attention and 4 items related to problematic behavior. Safety Issue: No
Classroom Observations
Time frame: On average, 8 and 13 months
To further assess functional improvement, at least two 15-minute classroom observations will be conducted by an intervention-blind research assistant (who has achieved reliability on coding criteria) for every study participant. They will occur randomly during the academic school day, but not during Flexible Futures small group sessions or Social Skills training. The following behaviors will be coded for children in this study: Reciprocity, Following Rules, Transitions, Gets Stuck, Negativity/Overwhelm, and Classroom Participation. During the classroom observations, the following behaviors will be coded for the teacher's behavior: Flexibility, Planning/Organizing, Provides Clear Instructions/ Expectations, Actively Uses Visual Support, References Classroom Rules, Maintains Positive Praise: Command/Correction ratio and Uses Reward System. Safety Issue: No
Cognitive Flexibility Task
Time frame: On average, 8 and 13 months
A task-based fMRI procedure will be used to detect pre-to-post treatment change. Participants will classify pairs of stimuli (objects and pictures) on the basis of how well they "go together" and respond with an appropriate button press. The specific task may change based on pilot results but will be similar to what is proposed. Safety Issue: No
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2020.
- Background: PubMed 23963592Pugliese CE, White SW. Brief report: problem solving therapy in college students with autism spectrum disorders: feasibility and preliminary efficacy. J Autism Dev Disord. 2014 Mar;44(3):719-29. doi: 10.1007/s10803-013-1914-8.
- Background: PubMed 8655658Pennington BF, Ozonoff S. Executive functions and developmental psychopathology. J Child Psychol Psychiatry. 1996 Jan;37(1):51-87. doi: 10.1111/j.1469-7610.1996.tb01380.x.
- Background: PubMed 22906000Frith U. Why we need cognitive explanations of autism. Q J Exp Psychol (Hove). 2012;65(11):2073-92. doi: 10.1080/17470218.2012.697178. Epub 2012 Aug 21.
- Background: PubMed 17404130Ganz ML. The lifetime distribution of the incremental societal costs of autism. Arch Pediatr Adolesc Med. 2007 Apr;161(4):343-9. doi: 10.1001/archpedi.161.4.343.
- BackgroundInteragency Autism Coordinating Committee. The 2011 Interagency Autism Coordinating Committee Strategic Plan for Autism Spectrum Disorder Research.; 2011.
- Background: PubMed 19455645Farley MA, McMahon WM, Fombonne E, Jenson WR, Miller J, Gardner M, Block H, Pingree CB, Ritvo ER, Ritvo RA, Coon H. Twenty-year outcome for individuals with autism and average or near-average cognitive abilities. Autism Res. 2009 Apr;2(2):109-18. doi: 10.1002/aur.69.
- BackgroundGobbo K, Shmulsky S. Faculty Experience With College Students With Autism Spectrum Disorders: A Qualitative Study of Challenges and Solutions. Focus Autism Other Dev Disabl. 2013;29(1):13-22. doi:10.1177/1088357613504989.
- Background: PubMed 24001150Taylor JL, Mailick MR. A longitudinal examination of 10-year change in vocational and educational activities for adults with autism spectrum disorders. Dev Psychol. 2014 Mar;50(3):699-708. doi: 10.1037/a0034297. Epub 2013 Sep 2.
- Background: PubMed 19430897Hume K, Loftin R, Lantz J. Increasing independence in autism spectrum disorders: a review of three focused interventions. J Autism Dev Disord. 2009 Sep;39(9):1329-38. doi: 10.1007/s10803-009-0751-2. Epub 2009 May 9.
- Background: PubMed 14697400Hill EL. Executive dysfunction in autism. Trends Cogn Sci. 2004 Jan;8(1):26-32. doi: 10.1016/j.tics.2003.11.003.
- Background: PubMed 25398602Pugliese CE, Anthony L, Strang JF, Dudley K, Wallace GL, Kenworthy L. Increasing adaptive behavior skill deficits from childhood to adolescence in autism spectrum disorder: role of executive function. J Autism Dev Disord. 2015 Jun;45(6):1579-87. doi: 10.1007/s10803-014-2309-1.
- Background: PubMed 24256459Kenworthy L, Anthony LG, Naiman DQ, Cannon L, Wills MC, Luong-Tran C, Werner MA, Alexander KC, Strang J, Bal E, Sokoloff JL, Wallace GL. Randomized controlled effectiveness trial of executive function intervention for children on the autism spectrum. J Child Psychol Psychiatry. 2014 Apr;55(4):374-83. doi: 10.1111/jcpp.12161. Epub 2013 Nov 21.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cara E Pugliese, Ph.D. principal investigator
Children's National Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Flexible Futures in people with Autism Spectrum Disorder, run by Children's National Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Behavior Rating Inventory of Executive Function (BRIEF)- Self-Report Form (Gioia, Isquith, Guy & Kenworthy, 2000). (time frame: On average, 8 and 13 months). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03199937, which also lists 71 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2020.