Buspirone Treatment of Anxiety in Williams Syndrome

NCT04807517 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2021P000376
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Williams Syndrome; Anxiety

Outcome Measures

Primary Outcomes (1)

• Mean 16-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score

  The Pediatric Anxiety Rating Scale (PARS) is a clinician-rated instrument that assesses anxiety symptoms that are commonly associated with social anxiety, separation anxiety, and generalized anxiety disorders. Scaled score ranges from 0-25 with higher scores indicating more severe anxiety symptoms. Mean change was estimated using a repeated measures linear regression model with time in categories as the covariate and all non-missing scores for all measurement times as outcomes. A linear contrast estimated mean change between Baseline and Week 16.

  Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported

Secondary Outcomes (5)

• 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)

  16 weeks

• Mean 16-Week Change in Child and Adolescent Symptom Inventory Anxiety-Modified Score

  Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported

• Mean 16-Week Change in Screen for Childhood Anxiety Related Emotional Disorders Total Score

  Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported

• Mean 16-Week Change in Each Subscale of the Aberrant Behavior Checklist

  Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported

• Mean 16-Week Change in Pittsburgh Sleep Quality Index Global Score

  Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported

Study Arms (1)

Buspirone

EXPERIMENTAL

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.

Drug: Buspirone

Interventions

Buspirone 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.

Buspirone

Eligibility Criteria

• Age: 5 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 5 to 65 years of age.
• Diagnosis of WS confirmed via genetic testing or a clinical diagnosis made by a clinician with significant experience treating patients with WS.
• A Clinical Global Impression Severity Item score ≥ 4 (moderate) for anxiety symptoms at Screen and Baseline.

You may not qualify if:

• 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).
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Lurie Center for Autism

Lexington, Massachusetts, 02421, United States

Location

MeSH Terms

Conditions

Williams Syndrome; Anxiety Disorders

Interventions

Buspirone

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Aortic Stenosis, Supravalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Mental Disorders

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds

Results Point of Contact

• Title: Lurie Center Research Manager
• Organization: Massachusetts General Hospital Lurie Center for Autism

luriecenterresearch@mgh.org

781-860-1711

Study Officials

• Robyn P Thom, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Study Record Dates

• First Submitted: March 17, 2021
• First Posted: March 19, 2021
• Study Start: August 1, 2021
• Primary Completion: September 11, 2023
• Study Completion: September 11, 2023
• Last Updated: December 3, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-11

Locations

US (1)