Summary

for people ages 8-12 (full criteria)
at Sacramento, California
study started
estimated completion
Marjorie Solomon, PH.D.

Description

Summary

Approximately 40%-80% of children and adolescents with autism spectrum disorder (ASD) exhibit clinically significant anxiety symptoms. These symptoms are associated with increased social deficits, depression, irritability, and stereotyped and self-injurious behaviors. Children and adolescents with anxiety also frequently avoid potentially stressful situations, thereby missing opportunities to learn important new skills. However, there is a lack of clarity about how to differentiate ASD and anxiety symptoms. There is also little known about how anxiety manifests in those with ASD and intellectual disability (ID). The goal of this study is to investigate these issues in order to make interventions more precise, more personalized, and more likely to promote positive outcomes While there is no doubt that anxiety is a very serious issue for those with ASD, what to do about this problem is less clear. Multiple small trials have provided promising evidence that selective serotonin reuptake inhibitors (SSRIs) and cognitive behavior therapy (CBT) might reduce anxiety in those with ASD. However, this work is in its early stages. In this study we will conduct a study in children with ASD and clinically significant anxiety ages 8-12 to compare efficacy of these different treatment types.

Official Title

Specifying and Treating the Anxiety Phenotype in Autism Spectrum Disorder

Details

Approximately 40%-80% of children and adolescents with autism spectrum disorder (ASD) exhibit clinically significant anxiety symptoms. These symptoms are associated with increased social deficits, depression, irritability, and stereotyped and self-injurious behaviors. Children and adolescents with anxiety also frequently avoid potentially stressful situations, thereby missing opportunities to learn important new skills. Despite the significant consequences of anxiety symptoms, several critical treatment-relevant issues remain unresolved. First, there is a lack of clarity about how to differentiate ASD and anxiety symptoms. Second, little is known about how anxiety manifests in those with ASD and intellectual disability (ID). Third, the neural substrates of anxiety in ASD are poorly understood. The overarching goal of this project is to investigate these open issues in order to make interventions more precise, more personalized, and more likely to promote positive outcomes -- an objective consistent with the National Institutes of Health (NIH), the Roadmap, Precision Medicine, and Research Domain Criteria Project (RDoC) Initiatives and the Interagency Autism Coordinating Committee (IACC) Strategic Plan, Chapter 4.

While there is no doubt that anxiety is a very serious issue for those with ASD, what to do about this problem is less clear. The search for empirically-validated treatments has begun with multiple small trials providing promising evidence that selective serotonin reuptake inhibitors (SSRIs) and cognitive behavior therapy (CBT) might reduce anxiety in those with ASD. However, this work is in its early stages. There is a great need for large, rigorously designed trials that validate the effectiveness of both medication and CBT, as well as functional neuroimaging studies that identify neural predictors of treatment efficacy and markers of therapy-induced change. Such work holds the potential to help answer the questions posed above and to assist the field in developing more personalized treatments. In Project 1 of the Center for the Development of Phenotype-Based Treatments of Autism Spectrum Disorder, we leverage the large, well-characterized UC Davis MIND Institute Autism Phenome Project (APP) cohort to conduct a comparative efficacy trial in N=132 participants (ages 8-12 years) with ASD and clinically significant anxiety.

Keywords

Autism Spectrum Disorder Anxiety cognitive behavior therapy functional neuroimaging Anxiety Disorders Autistic Disorder Child Development Disorders, Pervasive Sertraline CBT/BIACA

Eligibility

You can join if…

Open to people ages 8-12

  1. Outpatient boys and girls with ASD between ages 8-12 years at consent.
  2. Meets criteria for a diagnosis of ASD.
  3. Meets criteria for clinically significant anxiety symptoms as defined by a minimum score of 14 on the PARS Severity Scale.
  4. The child has a Full Scale and Verbal Comprehension IQ greater than 50 as assessed on the Wechsler Abbreviated Scales of Intelligence.
  5. Subjects with co-morbid depression, tic disorder or disruptive behavior disorders will be acceptable as long as the anxiety symptoms are considered the primary mental health problem (i.e., most impairing/distressing). (a) Eligibility will be guided by the following principle: For subjects presenting with comorbid symptomology, the co-morbid conditions cannot be sufficiently severe to: 1) warrant immediate treatment or require a change in an otherwise stable psychosocial treatment regimen for that disorder, or 2) potentially interfere with the child's ability to comply with the study assessment and treatment batteries. (b) Preliminary determination of acceptable eligibility will be made by the PI with consultation with clinical co-Investigators on the project. (c) Finally, each potential subject will be presented and discussed at weekly team meetings.
  6. The use of stable stimulant or alpha-agonist medications will be allowed if the dose has been consistent for 8 weeks and the family and treating psychiatrist affirm there is no plan to alter the dose or change medication in the foreseeable future.

You CAN'T join if...

  1. Receiving concurrent psychotherapy, social skills training that include homework, or behavioral interventions (e.g., applied behavior analysis). Families will have the option of discontinuing such services to enroll in the study. Other non-medication interventions will be allowed but we will document type and dose. This includes academic tutoring, occupational therapy, speech therapy, school counseling that is no more than 60 minutes per week in duration, school aides, and social skills training groups that do not include homework and are no more than 60 minutes/week in duration. Families of youth with ASD often have a variety of adjunctive services of this nature that they do not want to give up, and given the limited documentation of the efficacy of such interventions for social and emotional outcomes, it is deemed important to permit families to retain them in the service of recruiting a representative sample. If a potential participant is receiving non-allowed psychosocial treatments (psychotherapy, social skills training with homework, ABA) at the time of the phone evaluation and wishes to discontinue these treatments to enter the study, the patient will be asked to discuss this option with their clinician to determine whether termination would be safe and in the child's best interest. In addition, we will obtain the patient's written consent to contact their treating clinician to determine the appropriateness of study participation. We will not influence the decision patients make with their clinician. If non-allowed psychosocial treatments are discontinued, Gate B assessments will not be conducted until 1 month following termination.
  2. Child has failed a previous trial of sertraline judged adequate in dose (100mg/daily) and duration (at least 6 weeks) or child has a history of intolerance to sertraline. Subject has failed two previous SSRI (other than sertraline) trials judged adequate in dose (of 30mg/daily citalopram or paroxetine; 20mg/daily of escitalopram; 20mg/daily fluoxetine, 100mg/daily of fluvoxamine) and duration (6 weeks).
  3. Biological Treatments: Recent treatment with psychotropic medication within 12 weeks of study entry for antidepressants and within 6 weeks for neuroleptics. No new alternative medications, nutritionals or therapeutic diets within 6 weeks of study enrollment.
  4. Established Treatment changes: Any change in medication dosage (e.g., stimulant, alpha agonist) within 8 weeks before study enrollment will result in exclusion from the study. Any medications (e.g., stimulant) that the child is on must remain stable during treatment. If a potential participant is taking non-allowed psychotropic medication (antidepressants, antipsychotics) at the time of the phone evaluation and wishes to discontinue this medication to enter the study, the patient will be asked to discuss this option with their prescribing physician to determine whether medication discontinuation would be safe and in the child's best interest. In addition, we will obtain the patient's written consent to contact their treating clinician to determine the appropriateness of study participation. We will not influence the decision patients make with their prescribing physician. All pharmacotherapy recommendations will be made in consultation with the study physician. As described in Exclusion criterion 3, a specified waiting period would be required before the Gate B assessment should patients choose to discontinue non-allowed medications to enter the study.
  5. Current clinically significant suicidality or (b) individuals who have engaged in suicidal behaviors within 6 months will be excluded and referred for appropriate clinical intervention.
  6. Child has failed an adequate trial of CBT for anxiety within the previous 2 years (at least 10 sessions over a period of less than 1 year conducted by a licensed provider of CBT). This will be determined through records review and speaking with the clinician if appropriate.
  7. Lifetime DSM-5 bipolar disorder, schizophrenia or schizoaffective disorder as assessed by all forms of information (i.e., clinical history, data from the ADIS-IV, etc.).
  8. Child has a major neurological disorder or medical illness that requires a prohibited episodic or chronic systemic medication or that would interfere with study participation (e.g., frequent hospitalizations, frequent school absences).
  9. Child pregnancy as indicated by history or positive pregnancy test.
  10. . Inability to safely swallow study mediation after pill swallowing education.
  11. . Contraindications to MRI (i.e. claustrophobia, extreme sensitivity to noise, metal in the body).
  12. . Excess motion during scanning even after 2-3 training sessions.

Location

  • UC Davis MIND Institute accepting new patients
    Sacramento California 95817 United States

Lead Scientist

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, Davis
Links
Sign up for this study
ID
NCT03279471
Phase
Phase 2
Study Type
Interventional
Last Updated