Clinical trial NCT04807517: Buspirone Treatment of Anxiety in Williams Syndrome
Official title: Buspirone for the Treatment of Anxiety in Williams Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Williams Syndrome
Anxiety
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2021-03-19
Enrollment: 20
Sex: ALL
Minimum age (years): 5
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to do a preliminary assessment of whether buspirone is effective, safe, and tolerable in the treatment of anxiety in children, adolescents, and adults with Williams syndrome.

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, open-label trial of buspirone. 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.

Eligibility criteria: Inclusion Criteria:

1. Age 5 to 65 years of age.
2. Diagnosis of WS confirmed via genetic testing or a clinical diagnosis made by a clinician with significant experience treating patients with WS.
3. Clinically significant anxiety as evidenced by a Pediatric Anxiety Rating Scale (PARS) score of 10 or greater (5-item scale). The PARS ("The Pediatric Anxiety Rating Scale (PARS): Development and psychometric properties." 2002) was chosen as an inclusion criterion (and outcome measure) since it assesses severity across common anxiety disorders in children including generalized anxiety, social anxiety, separation anxiety, and transition-associated anxiety. In addition, it is an instrument that allows the clinician to incorporate both child and parent report into a final clinician-rated score for each item.
4. A Clinical Global Impression Severity Item score ≥ 4 (moderate) for anxiety symptoms at Screen and Baseline.

Exclusion Criteria:

1. Diagnosis of OCD, posttraumatic stress disorder, major mood disorder, psychotic disorder, or substance use disorder. These disorders are exclusionary since the primary treatment of these disorders may require acute psychosocial treatments or other medications that would confound the assessments.
2. Presence of any past or present conditions that would make treatment with buspirone unsafe. This includes allergy to buspirone, liver or kidney disease, and pregnancy (or being sexually active without using acceptable methods to prevent pregnancy).
3. Use of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), benzodiazepines, antihistamines (as needed use of an antihistamine for the treatment of allergies will be permitted), or antipsychotics. Subjects will need to be off medications from these classes for at least 5 elimination half-lives prior to beginning the trial.
4. Use of other psychotropic medications which are ineffective, poorly tolerated, or sub-optimal in terms of dose. A board-certified child and adolescent psychiatrist will assess any other psychotropic medications being used and determine whether they are effective, tolerated, and optimal in terms of dose. Concurrent use of a psychotropic medication (other than SSRIs, SNRIs, benzodiazepines, antihistamines, or antipsychotics) will be allowed if the dose has been stable for 30 days and if they meet the criteria of effectiveness, tolerability, and dose.
5. Previous adequate trial of buspirone. An adequate trial will be defined as a total daily dose of ≥20 mg for at least 4 weeks. In addition, subjects who developed significant adverse effects during a trial of buspirone at any dose or duration will be excluded.
6. Severe or profound intellectual disability based on clinical assessment and review of standardized assessment of cognitive skills. Subjects will undergo standardized testing and be evaluated by study staff to determine cognitive capabilities. Participants determined to have severe or profound intellectual disability will be excluded.

Primary outcomes:
measure: Mean 16-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported
Secondary outcomes:
measure: Proportion of Participants Who Responded to Treatment at 16 Weeks According to the Improvement Item of the Clinical Global Impression-Scale (Response Defined as CGI-I=1 or CGI-I=2)
timeFrame: 16 weeks
measure: Mean 16-Week Change in Child and Adolescent Symptom Inventory Anxiety-Modified Score
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported
measure: Mean 16-Week Change in Screen for Childhood Anxiety Related Emotional Disorders Total Score
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported
measure: Mean 16-Week Change in Each Subscale of the Aberrant Behavior Checklist
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported
measure: Mean 16-Week Change in Pittsburgh Sleep Quality Index Global Score
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported
Other outcomes:
Locations:
city: Lexington
country: United States
facility: Lurie Center for Autism
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Robyn P Thom, MD
role: PRINCIPAL_INVESTIGATOR
References: