Specifying and Treating Anxiety in Autism Research

NCT ID: NCT03279471

Last Updated: 2023-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-01

Study Completion Date

2023-02-22

Brief Summary

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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

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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.

Conditions

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Autism Spectrum Disorder Anxiety

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

3 Arm trial comparing manualized CBT/social skills training versus sertraline versus pill placebo
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
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

Study Groups

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CBT/BIACA

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.

Group Type EXPERIMENTAL

CBT/BIACA

Intervention Type BEHAVIORAL

Participants receive 16 weeks of BIACA therapy.

Sertraline

These participants will receive sertraline

Group Type ACTIVE_COMPARATOR

Sertraline

Intervention Type 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.

Pill Placebo

These individuals will receive a pill placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Sertraline

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.

Intervention Type DRUG

CBT/BIACA

Participants receive 16 weeks of BIACA therapy.

Intervention Type BEHAVIORAL

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Outpatient boys and girls with ASD between ages 8-14 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 8 on the PARS Severity Scale.
4. Meets criteria for clinically significant anxiety symptoms as defined by qualifying for diagnosis on 1 or more non-phobia items on the ADIS.
5. The child has a Verbal Comprehension IQ greater than 50 as assessed on the Wechsler Abbreviated Scales of Intelligence or other standardized cognitive measure.
6. Anxiety symptoms are considered the primary mental health problem (i.e., most impairing/distressing)
7. Stable medication regimen for 8 weeks prior to screening visit, including alternative medication, nutritionals, or therapeutic diets.
8. Stable non-psychotherapy regimen for 4 weeks prior to screening visits. Non-psychotherapy regimen may include:

1. Academic tutoring
2. Occupational therapy
3. Speech therapy
4. School aides
9. Stable psychosocial treatment regimen for 4 weeks prior to screening visits. Allowed psychosocial treatments may include:

1. School counseling (no more than 60 minutes per week in duration)
2. Psychotherapy
3. Social skills training
4. Applied behavior analysis (ABA) (up to 10 hours per week)

Exclusion Criteria

1. 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.
2. 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.

1. Sertraline - 100mg/daily
2. Citalopram or paroxetine - 30mg/daily
3. Escitalopram - 20mg/daily
4. Fluoxetine - 20mg/daily
5. Fluvoxamine - 100mg/daily
3. 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.
4. 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.
5. 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.).
6. 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.
7. 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).
8. Child pregnancy as indicated by history or positive pregnancy test.
9. Inability to safely swallow study medication after pill swallowing education.
10. Child and parent/caregiver who do not speak English.
Minimum Eligible Age

8 Years

Maximum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of California, Davis

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marjorie Solomon, PH.D.

Role: PRINCIPAL_INVESTIGATOR

UC Davis

Locations

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UC Davis MIND Institute

Sacramento, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 16845581 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18645422 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21735077 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19223098 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25524571 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 11708587 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27349358 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25602249 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24167175 (View on PubMed)

Related Links

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Other Identifiers

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1097281

Identifier Type: -

Identifier Source: org_study_id