Anxiety, Autism Spectrum Disorder
Conditions
Keywords
buspirone, anxiety, autism, autism spectrum disorder, randomized controlled trial
Brief summary
The purpose of the study is to do a preliminary trial to determine if buspirone is effective, safe, and tolerable in autistic youth with anxiety.
Detailed description
After being informed about the study and potential risks, all patients or their legal guardians giving written informed consent will be screened for study eligibility. Patients who meet the eligibility requirements will participate in a 16-week, flexibly-dosed, randomized controlled trial of buspirone versus placebo. The dose of buspirone will be adjusted over the first 12 weeks of the study and a stable dose will be maintained for the final four weeks of the trial. Adverse effects will be reviewed at each visit and standardized measures of anxiety will be conducted at weeks 4, 8, 12, and 16.
Interventions
DRUGbuspirone
Buspirone, an anxiety medication that is FDA approved for generalized anxiety disorder in adults, will be the active comparator for this trial.
DRUGPlacebo
Matching placebo capsules/liquid formulation will be prepared.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Age 7-17 years 2. Diagnosis of Autism Spectrum Disorder (ASD) confirmed by the study clinician using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and Social Communication Questionnaire (SCQ) 3. Diagnosis of social phobia, separation anxiety disorder, or generalized anxiety disorder of at least moderate severity based on the Anxiety and Related Disorders Interview Schedule (ADIS), 5-item Pediatric Anxiety Rating Scale (PARS) score ≥10, and Clinical Global Impression Severity subscale (CGI-S) ≥4 4. IQ ≥50 based on Stanford Binet, 5th Edition Abbreviated IQ test or the Kaufman Brief Intelligence Test, 2nd Edition (KBIT-2) 5. Stable medications for ≥30 days 6. English speaking 7. Ability to swallow buspirone capsules or liquid suspension
Exclusion criteria
1. Known diagnosis of a genetic syndrome associated with ASD (e.g. Fragile X syndrome, Angelman syndrome) based on parent report 2. Known cardiac arrythmia based on parent report 3. Current primary diagnosis of bipolar disorder, psychosis, substance use disorder, posttraumatic stress disorder, eating disorder, or major depressive disorder in the opinion of the PI 4. Any past or present conditions that would make treatment with buspirone unsafe 5. Current use of any of the following psychotropic medications: SSRIs, SNRIs, mirtazapine, benzodiazepines, tricyclic antidepressants, monoamine oxidase inhibitors, mood stabilizers, or antipsychotics 6. Previous adequate trial of buspirone (≥20 mg/day for at least 4 weeks) or significant adverse effects 7. Aberrant Behavior Checklist Irritability subscale score (ABC-I) ≥18 8. Pregnancy or sexual activity without the use of an acceptable form of birth control in females of childbearing age 9. Acutely unstable medical/psychiatric condition (e.g. self-injury, suicidality) that would preclude study participation in the opinion of the PI 10. Inability to tolerate Bittium Faros device in the opinion of the parent or a known allergy to adhesives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean 16-Week Change in Pediatric Anxiety Rating Scale (PARS) 5-Item Total Score | Baseline, Week 4, Week 8, Week 2, Week 16; Change from Baseline to Week 16 reported | The PARS, a clinician-administered measure of child anxiety symptom severity based on both patient and parent-report will be the primary outcome measure. It has demonstrated inter-rater and test-retest reliability, and has previously been used by our group as the primary outcome measure in a RCT of mirtazapine for anxiety in youth with ASD, demonstrating sensitivity to change. The 5-item PARS score will be the primary outcome measure for this trial. Scaled score ranges from 0-25 with higher scores indicating more severe anxiety symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants who Responded to Treatment at 16 Weeks According to the Improvement Item of the Clinical Global Impression-Improvement (CGI-I) (Response Defined as CGI-I = 1 or 2) | Week 4, Week 8, Week 12, Week 16. Week 16 score reported. | The Clinical Global Impressions Global Improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7 (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse), with lower scales indicating improvement (1=very much improved; 2=much improved). In this study, the CGI-I will be focused on the target symptom of anxiety. Participants with a CGI-I score of 1 or 2 will be classified as responders. |
| Mean 16-Week Change in Clinical Global Impression Severity Subscale (CGI-S) | Baseline, Week 4, Week 8, Week 12, Week 16. Change from Baseline to Week 16 reported. | The CGI-S is rated on a scale from 1 to 7, where 1 = normal, not at all ill; 3 = mildly ill; 5 = markedly ill; 7 = among the most extremely ill patients. The CGI-S will be rated based on the severity of anxiety symptoms. |
| Mean 16-Week Change in Parent-Rated Anxiety Scale for Autism Spectrum Disorder (PRAS-ASD) Score | Baseline, Week 8, Week 16. Change from Baseline to Week 16 reported. | The PRAS-ASD is a novel parent-rated 25-item scale with demonstrated reliability and validity. Scores range from 0-75, with higher scores indicating more severe parent-rated anxiety. |
Countries
United States
Contacts
CONTACTRobyn P. Thom, MD
Outcome results
None listed