Specifying and Treating Anxiety in Autism Research

NCT03279471 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1097281
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

In the Specifying and Treating the Anxiety Phenotype in Autism Spectrum Disorder (STAAR) study, we conducted a16-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 involved 2-3 half day telehealth visits for behavioral and medical assessments, 1-2 lab visits for safety testing, and 1-2 optional fMRI (functional magnetic resonance imaging) visits for participants before the pandemic made this impossible. The study provided 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 was conducted and participants in the placebo group were given the option to participate in an additional study phase with the study treatment of their choice. Study participation could be done remotely through the use of telehealth and local labs, meaning that visits to the University of California (UC) Davis MIND Institute were not required for most participants. Several changes were made to the original protocol after the initiation of the COVID-19 Pandemic in mid-March of 2020. While the IRB of UCDMC deemed our study to be essential and permitted us to continue both psychosocial CBT therapy and medication administration, they required that:

1. 1.Assessment measures that had been implemented in person, be switched to online or Zoom administration.
2. 2.It also became impossible to administer the Autism Diagnostic Observation Scale (ADOS) in a valid manner. We then used the Childhood Autism Rating Scale (CARS-2) as the basis for qualification for the study.
3. 3.We were no longer able to see participants in person so Cognitive Behavior Therapy visits were moved to an online format.
4. 4.Similarly, medication visits were conducted over Zoom unless it was necessary to have the participant come into our clinic such as in the initial assessment or for safety concerns.
5. 5.In the Medication Arm, we partnered with Quest Labs to enable participants to receive their safety monitoring blood tests in the community.
6. 6.Unfortunately, it became extremely difficult to recruit patients willing to be scanned so we halted the fMRI component of the study.

Conditions

Autism Spectrum Disorder; Anxiety

Keywords

autism spectrum disorder; anxiety; cognitive behavior therapy; functional neuroimaging; STAAR; ASD; MIND Institute; UC Davis; MIND; University of California, Davis; autism

Outcome Measures

Primary Outcomes (1)

• Change in Pediatric Anxiety Rating Scale

  The Pediatric Anxiety Rating Scale (PARS) is a clinician-rated scale assessing anxiety symptoms and the associated severity and impairment in children over the past week in 6 to 17 year olds. PARS is the one primary outcome measure used in this study. It is administered by a trained clinician who queries the participant's parent about anxiety symptoms experienced by the child and their associated severity and impairment over the past week. The first section is a Symptom Checklist with 50 items assessing 7 categories of anxiety symptoms on a 5-point scale. Given that some of these categories (number of symptoms and physical symptoms) don't directly bear on severity and/or may capture medication effects, they are not included in the final 5 Severity Score domains used in the overall calculation. Thus, scores on the PARS Severity Scale range from 0 to 25, with scores \>14 consistent with clinically significant levels of anxiety in youth with ASD.

  Change from baseline to week 17 (treatment completion)

Study Arms (3)

CBT/BIACA

EXPERIMENTAL

These participants will receive CBT treatment using Behavioral Interventions for Anxiety in Children with Autism (BIACA). BIACA is an anxiety treatment package designed for children with ASD that includes elements of CBT and social skills training.

Behavioral: CBT/BIACA

Sertraline

ACTIVE COMPARATOR

These participants will receive sertraline

Drug: Sertraline

Pill Placebo

PLACEBO COMPARATOR

These individuals will receive a pill placebo.

Drug: Placebo

Interventions

Sertraline DRUG

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.

Sertraline

CBT/BIACA BEHAVIORAL

Participants receive 16 weeks of BIACA therapy.

CBT/BIACA

Placebo DRUG

Participants are given a placebo capsule with an administration schedule matching that of the sertraline subjects.

Pill Placebo

Eligibility Criteria

• Age: 8 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Outpatient boys and girls with ASD between ages 8-14 years at consent.
• Meets criteria for a diagnosis of ASD.
• Meets criteria for clinically significant anxiety symptoms as defined by a minimum score of 8 on the PARS Severity Scale.
• Meets criteria for clinically significant anxiety symptoms as defined by qualifying for diagnosis on 1 or more non-phobia items on the ADIS.
• The child has a Verbal Comprehension IQ greater than 50 as assessed on the Wechsler Abbreviated Scales of Intelligence or other standardized cognitive measure.
• Anxiety symptoms are considered the primary mental health problem (i.e., most impairing/distressing)
• Stable medication regimen for 8 weeks prior to screening visit, including alternative medication, nutritionals, or therapeutic diets.
• Stable non-psychotherapy regimen for 4 weeks prior to screening visits. Non-psychotherapy regimen may include:
• Academic tutoring
• Occupational therapy
• Speech therapy
• School aides
• Stable psychosocial treatment regimen for 4 weeks prior to screening visits. Allowed psychosocial treatments may include:
• School counseling (no more than 60 minutes per week in duration)
• Psychotherapy

You may not qualify if:

• Subject is receiving significant concurrent psychosocial treatment with the primary aim to treat the child's anxiety.
• a. Families will have the option of discontinuing such services to enroll in the study. If a potential participant is receiving non-allowed treatments 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. We will not influence the decision patients make with their clinician.
• History of intolerance to sertraline OR previous unsuccessful treatment with sertraline or other SSRIs judged adequate in dose (per list below) and taken for at least 6 weeks, within the past 12 months.
• Sertraline - 100mg/daily
• Citalopram or paroxetine - 30mg/daily
• Escitalopram - 20mg/daily
• Fluoxetine - 20mg/daily
• Fluvoxamine - 100mg/daily
• Current clinically significant suicidal behaviors with intent or plan or individuals who have engaged in suicidal behaviors within 6 months. Study physicians will direct patient to appropriate clinical care if these behaviors are seen.
• Child has unsuccessful treatment for anxiety using a manualized CBT program 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 parent report, records review and speaking with the clinician if appropriate.
• 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.).
• Abnormal laboratory or electrocardiogram results at screening that are in the opinion of the investigator clinically significant and may jeopardize the safety of the study subject.
• Child has a major neurological disorder or medical illness that requires a prohibited episodic or chronic systemic medication that might interfere with the absorption, distribution, metabolism, or excretion of the study medication places the subject at increased risk, or that would interfere with study participation (e.g., frequent hospitalizations, frequent school absences).
• Child pregnancy as indicated by history or positive pregnancy test.
• Inability to safely swallow study medication after pill swallowing education.

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

UC Davis MIND Institute

Sacramento, California, 95817, United States

Location

Related Publications (9)

• Leyfer OT, Folstein SE, Bacalman S, Davis NO, Dinh E, Morgan J, Tager-Flusberg H, Lainhart JE. Comorbid psychiatric disorders in children with autism: interview development and rates of disorders. J Autism Dev Disord. 2006 Oct;36(7):849-61. doi: 10.1007/s10803-006-0123-0.

  PMID: 16845581 BACKGROUND

• Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry. 2008 Aug;47(8):921-9. doi: 10.1097/CHI.0b013e318179964f.

  PMID: 18645422 BACKGROUND

• van Steensel FJ, Bogels SM, Perrin S. Anxiety disorders in children and adolescents with autistic spectrum disorders: a meta-analysis. Clin Child Fam Psychol Rev. 2011 Sep;14(3):302-17. doi: 10.1007/s10567-011-0097-0.

  PMID: 21735077 BACKGROUND

• White SW, Oswald D, Ollendick T, Scahill L. Anxiety in children and adolescents with autism spectrum disorders. Clin Psychol Rev. 2009 Apr;29(3):216-29. doi: 10.1016/j.cpr.2009.01.003. Epub 2009 Jan 25.

  PMID: 19223098 BACKGROUND

• Bishop-Fitzpatrick L, Mazefsky CA, Minshew NJ, Eack SM. The relationship between stress and social functioning in adults with autism spectrum disorder and without intellectual disability. Autism Res. 2015 Apr;8(2):164-73. doi: 10.1002/aur.1433. Epub 2014 Dec 19.

  PMID: 25524571 BACKGROUND

• Gillott A, Furniss F, Walter A. Anxiety in high-functioning children with autism. Autism. 2001 Sep;5(3):277-86. doi: 10.1177/1362361301005003005.

  PMID: 11708587 BACKGROUND

• Craske MG, Stein MB. Anxiety. Lancet. 2016 Dec 17;388(10063):3048-3059. doi: 10.1016/S0140-6736(16)30381-6. Epub 2016 Jun 24.

  PMID: 27349358 BACKGROUND

• Vasa RA, Mazurek MO. An update on anxiety in youth with autism spectrum disorders. Curr Opin Psychiatry. 2015 Mar;28(2):83-90. doi: 10.1097/YCO.0000000000000133.

  PMID: 25602249 BACKGROUND

• Sukhodolsky DG, Bloch MH, Panza KE, Reichow B. Cognitive-behavioral therapy for anxiety in children with high-functioning autism: a meta-analysis. Pediatrics. 2013 Nov;132(5):e1341-50. doi: 10.1542/peds.2013-1193. Epub 2013 Oct 28.

  PMID: 24167175 BACKGROUND

Related Links

• Learn more or sign up for the study here!

MeSH Terms

Conditions

Autism Spectrum Disorder; Anxiety Disorders; Autistic Disorder

Interventions

Sertraline

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Marjorie Solomon
• Organization: University of California, Davis

marsolomon@ucdavis.edu

916-703-0270

Study Officials

• Marjorie Solomon, PH.D.

  UC Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: participants do not know what interventions others receive; med arm care providers don't know what interventions their patients receive; assessors don't know what treatments the participants they asses receive
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3 Arm trial comparing manualized CBT/social skills training versus sertraline versus pill placebo

Study Record Dates

• First Submitted: August 28, 2017
• First Posted: September 12, 2017
• Study Start: October 1, 2017
• Primary Completion: February 22, 2023
• Study Completion: February 22, 2023
• Last Updated: September 23, 2026
• Results First Posted: September 23, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)