Specifying and Treating the Anxiety Phenotype in Autism Spectrum Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Change in Pediatric Anxiety Rating Scale
研究概览
简要总结
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:
- Assessment measures that had been implemented in person, be switched to online or Zoom administration.
- 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.
- We were no longer able to see participants in person so Cognitive Behavior Therapy visits were moved to an online format.
- 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.
- In the Medication Arm, we partnered with Quest Labs to enable participants to receive their safety monitoring blood tests in the community.
- Unfortunately, it became extremely difficult to recruit patients willing to be scanned so we halted the fMRI component of the study.
详细描述
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, 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 conducted a study in children with ASD and clinically significant anxiety ages 8-14 to compare efficacy of these different treatment types.
More specifically, the overall aim of the study was to conduct 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 (intelligence quotient) >50, and clinically significant anxiety as assessed by a PARS score that is greater than or equal to 8. PARS is the primary outcome measures for the trial. Other prespecified measures such as clinician-administered gold standard assays will be used of traditional DSM (Diagnostic and Statistical Manual) [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)] to qualify participants. We also used additional prespecified measures including parent reports of potentially overlapping symptoms that complicate the ASD anxiety phenotype. Although we additionally had wanted to include fMRI to investigate neural predictors of treatment efficacy, markers of treatment induced change, and signatures of anxiety sub-types, these efforts needed to be stopped due to the pandemic.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
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
入排标准
- 年龄范围
- 8 Years 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Social skills training
- •Applied behavior analysis (ABA) (up to 10 hours per week)
排除标准
- •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.
- •Child and parent/caregiver who do not speak English.
研究组 & 干预措施
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.
干预措施: CBT/BIACA (Behavioral)
Pill Placebo
These individuals will receive a pill placebo.
干预措施: Placebo (Drug)
Sertraline
These participants will receive sertraline
干预措施: Sertraline (Drug)
结局指标
主要结局
Change in Pediatric Anxiety Rating Scale
时间窗: Change from baseline to week 17 (treatment completion)
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.
次要结局
未报告次要终点