Buspirone Treatment of Anxiety in Williams Syndrome

NCT ID: NCT04807517

Last Updated: 2024-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-01
• Study Completion Date: 2023-09-11

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.

Conditions

Williams Syndrome; Anxiety

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Buspirone

Subjects will receive buspirone 2.5 mg each morning at the start of the trial. The dose will be increased by 2.5 mg per week in two divided doses daily depending on effectiveness and tolerability. The optimal dose will be reached by week 12 of treatment. The minimum starting dose will be 2.5 mg and the maximum total daily dose will be 30 mg. Medication will be dosed twice daily due to the short half-life (2-3 hours) of this medication.

Group Type: EXPERIMENTAL

Buspirone

Intervention Type: DRUG

All participants in the study will receive open-label treatment with orally administered buspirone for the full duration of the 16-week trial. Buspirone has high affinity for serotonin 5-HT1A and 5-HT2 receptors and moderate affinity for dopamine D2 receptors. It is approved for the management of generalized anxiety disorder in adults.

Interventions

Buspirone

All participants in the study will receive open-label treatment with orally administered buspirone for the full duration of the 16-week trial. Buspirone has high affinity for serotonin 5-HT1A and 5-HT2 receptors and moderate affinity for dopamine D2 receptors. It is approved for the management of generalized anxiety disorder in adults.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Robyn P. Thom, M.D.

Assistant Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robyn P Thom, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Lurie Center for Autism

Lexington, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2021P000376

Identifier Type: -

Identifier Source: org_study_id