Specifying and Treating Anxiety in Autism Research
Condition: Autism Spectrum Disorder; Anxiety
MeSH terms: Anxiety Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Interventional
Phase: Phase 2

Summary: 
      The Specifying and Treating the Anxiety Phenotype in Autism Spectrum Disorder (STAAR) study
      aims to better characterize the sub-group of children and preadolescents with ASD that
      exhibit clinically significant anxiety by conducting a 16-week randomized comparative
      treatment trial of the Behavioral Intervention for Anxiety in Children with Autism (BIACA),
      the medication sertraline, and placebo in youth with ASD ages 8-14 years old. The study
      involves 2-3 half day telehealth visits for behavioral and medical assessments, 1-2 lab
      visits for safety testing, and 1-2 optional fMRI visits. The study provides 16-weeks of
      anxiety treatment involving weekly BIACA therapy either in-person or through telehealth, or
      medical check-up visits either at the UC Davis MIND Institute or via telehealth. After study
      completion a 3 month follow up call is conducted and participants in the placebo group are
      given the option to participate in an additional study phase with the study treatment of
      their choice. Study participation can be done remotely through the use of telehealth and
      local labs, visits to the UC Davis MIND Institute are not required for most participants.
    

Detailed description: 
      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 will conduct a study in children with ASD and clinically significant anxiety ages 8-14 to
      compare efficacy of these different treatment types.

      The overall aims of the study are to better characterize the sub-group of children and
      preadolescents with ASD that exhibit clinically significant anxiety and fears through a
      16-week randomized comparative treatment trial of Behavioral Intervention for Anxiety in
      Children with Autism (BIACA), sertraline, and placebo in youth with ASD, IQ>50, and
      clinically significant anxiety as assessed by a PARS score that is greater than or equal to
      8. Clinician-administered gold standard assays will be used of traditional DSM (Pediatric
      Anxiety Rating Scale [PARS] and the Anxiety Disorders Interview Schedule-IV [ADIS-IV]), and
      nontraditional ASD related anxiety symptoms (Autism Spectrum Addendum to the ADIS [ASDD]), as
      well as parent reports of potentially overlapping symptoms that complicate the ASD anxiety
      phenotype. Additionally fMRI will be used to investigate neural predictors of treatment
      efficacy, markers of treatment induced change, and signatures of anxiety sub-types.
    

Intervention name(s): Sertraline; CBT/BIACA; Placebo
Intervention type(s): Drug; Behavioral; Drug
Intervention description(s): Participants start at 12.5 mg and are increased by 12.5/day every two weeks for 14-16 weeks based on their tolerability to the medication. Dosing is capped at 125mg/day.; Participants receive 16 weeks of BIACA therapy.; Participants are given a placebo capsule with an administration schedule matching that of the sertraline subjects.
Intervention MeSH terms: Sertraline
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 3 Arm trial comparing manualized CBT/social skills training versus sertraline versus pill placebo
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: autism spectrum disorder; anxiety; cognitive behavior therapy; functional neuroimaging; STAAR; ASD; MIND Institute; UC Davis; MIND; UCD; autism