Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Buspirone | Active Comparator |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| buspirone | Drug | Buspirone, an anxiety medication that is FDA approved for generalized anxiety disorder in adults, will be the active comparator for this trial. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean 16-Week Change in Pediatric Anxiety Rating Scale (PARS) 5-Item Total Score | 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. | Baseline, Week 4, Week 8, Week 2, Week 16; Change from Baseline to Week 16 reported |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Irritability Subscale Score | The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Irritability Subscale is derived from 15 items, with a score range from 0-45, where higher scores indicate more severe irritability. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Robyn P. Thom, MD | Contact | 781-860-1711 | luriecenterresearch@mgb.org |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D000067877 | Autism Spectrum Disorder |
| D001321 | Autistic Disorder |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D002065 | Buspirone |
| ID | Term |
|---|---|
| D013141 | Spiro Compounds |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Matching placebo capsules/liquid formulation will be prepared. |
|
| Week 4, Week 8, Week 12, Week 16. Week 16 score reported. |
| Mean 16-Week Change in Clinical Global Impression Severity Subscale (CGI-S) | 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. | Baseline, Week 4, Week 8, Week 12, Week 16. Change from Baseline to Week 16 reported. |
| Mean 16-Week Change in Parent-Rated Anxiety Scale for Autism Spectrum Disorder (PRAS-ASD) Score | 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. | Baseline, Week 8, Week 16. Change from Baseline to Week 16 reported. |
| Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Lethargy/Social Withdrawal Subscale Score | The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Lethargy/Withdrawal Subscale is derived from 16 items, with a score range from 0-48 where higher scores indicate more severe Lethargy/Withdrawal symptoms. | Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Stereotypic Behavior Subscale Score | The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Stereotypic Behavior Subscale is derived from 7 items, with a score range of 0-21 where higher scores indicate more severe stereotypic behaviors. | Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Hyperactivity Subscale Score | The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Hyperactivity Subscale is derived from 16 items with a score range of 0-48, where severe scores indicate more severe hyperactivity symptoms. | Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Inappropriate Speech Subscale Score | The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Inappropriate Speech Subscale is derived from 4 items with a score range of 0-12, where higher scores indicate more severe Inappropriate Speech symptoms. | Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) Score | The ADHD-RS is an 18-question, parent-rated assessment reflecting DSM symptoms of ADHD. The score range is 0-54, with higher scores indicating more severe ADHD symptoms. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Children's Sleep Habits Questionnaire (CSHQ) Total Score | The CSHQ is a 52-question parent survey used to assess sleep difficulties. 33 items are used to generate the total score, which ranges from 33-99, with a cutoff of >41 suggesting clinically significant sleep problems. Higher scores are indicative of more severe sleep problems. | Baseline, Week 16; Change from Baseline to Week 16 is reported |
| Mean 16-Week Change in Heart Rate Variability (HRV) at Rest | The log[root mean square of successive differences (RMSSD)] will be utilized as the primary HRV measure. It will be measured at rest in the laboratory setting pre- and post-treatment. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Heart Rate Variability (HRV) with Startle | The log[root mean square of successive differences (RMSSD)] will be utilized as the primary HRV measure. It will be measured during a startle tone in the laboratory setting pre- and post-treatment. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Heart Rate Variability (HRV) During a Working Memory Task | The log[root mean square of successive differences (RMSSD)] will be utilized as the primary HRV measure. It will be measured during a working memory task in the laboratory setting pre- and post-treatment. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Heart Rate Variability (HRV) During Cold Pressor Task | The log[root mean square of successive differences (RMSSD)] will be utilized as the primary HRV measure. It will be measured during the Cold Pressor Task in the laboratory setting pre- and post-treatment. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Blood Pressure | Blood pressure will be measured at rest in the laboratory setting pre- and post-treatment. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Skin Conductance Level at Rest | Skin conductance level will be measured at rest in the laboratory setting pre- and post-treatment. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Skin Conductance Level with Startle | Skin conductance level will be measured during a startle tone in the laboratory setting pre- and post-treatment. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Skin Conductance Level During Working Memory Task | Skin conductance level will be measured during a working memory task in the laboratory setting pre- and post-treatment. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Skin Conductance Level During Cold Pressor Task | Skin conductance level will be measured during the Cold Pressor Task in the laboratory setting pre- and post-treatment. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Ambulatory Heart Rate Variability | Heart rate variability (HRV) will be assessed remotely throughout the 16-week trial using the Bittium Faros holter monitor. Change in log[root mean square of successive differences (RMSSD)] over the course of the trial will be quantified. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| Mean 16-Week Change in Ambulatory Accelerometry Magnitude | Accelerometry magnitude will be assessed remotely throughout the 16-week trial using the Bittium Faros holter monitor, which records acceleration vector components (x, y, and z). Accelerometry magnitude (m/s^2) will be calculated using the vector sum of the acceleration vector components. Change in accelerometry magnitude over the course of the trial will be quantified. | Baseline, Week 16; Change from Baseline to Week 16 reported |
| D010879 |
| Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D011083 | Polycyclic Compounds |