Williams SyndromePhase 4NCT04807517
Buspirone Treatment of Anxiety in Williams Syndrome
A Phase 4 study testing Buspirone in people with Williams Syndrome and Anxiety, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 65 years
- Conditions the study is for
- Williams Syndrome, Anxiety
- What is being tested?
- Buspirone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2021to 11 Sep 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- 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.
- A Clinical Global Impression Severity Item score ≥ 4 (moderate) for anxiety symptoms at Screen and Baseline.
Who cannot join
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lurie Center for Autism
Lexington, Massachusetts, 02421
About this study
Official title: Buspirone for the Treatment of Anxiety in Williams Syndrome
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.
Read the 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
- Being tested
- Buspirone
- Medical subject headings
- Williams Syndrome, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuspironeDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Buspirone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: 16 weeks
Mean 16-Week Change in Child and Adolescent Symptom Inventory Anxiety-Modified Score
The Child and Adolescent Symptom Inventory (CASI) is a caregiver completed questionnaire with items that map directly onto Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria for anxiety disorders in children and adolescents. The CASI-Modified which includes 20 specific items that have been used to assess anxiety in subjects with developmental disabilities will be administered. Total score ranges from 0-20 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.
Measured: 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
The Screen for Childhood Anxiety Related Emotional Disorders (SCARED) includes both a child/self-report and parent-report form, each containing 41-items. It is used to screen for symptoms of panic disorder, separation anxiety disorder, social phobia, generalized anxiety disorder, and school phobia. Total score ranges from 0-82 and a total score of 25 or greater may indicate the presence of an anxiety disorder. 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.
Measured: 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
The Aberrant Behavior Checklist (ABC-2) is a caregiver rated instrument that measures psychiatric symptoms and behavioral disturbance in subjects with developmental disability with 5 subscales. Each of its 58 items is scored on a 4-point scale (0=never a problem to 3=severe problem). The 5 subscales and their range of scores are: Irritability 0-45, with higher scores indicating more severe irritability; Social Withdrawal/Lethargy 0-48, with higher scores indicating more severe social withdrawal; Stereotypy 0-21, with higher scores indicating more severe stereotypy; Hyperactivity 0-48, with higher scores indicating more severe hyperactivity; Inappropriate Speech 0-12, with high scores indicating more severe inappropriate speech. 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.
Measured: 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
The Pittsburgh Sleep Quality Index (PSQI) questionnaire that will be completed by the subject's caregiver to assess sleep quality. The global score ranges from 0-21, where a higher score indicates greater sleep difficulty. 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.
Measured: Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start1 Aug 2021
- Primary completion11 Sep 2023
- Study completion11 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Williams SyndromeStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robyn P. Thom, M.D., Massachusetts General Hospital
- Investigators
- Robyn P Thom, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04807517
- Sponsor's protocol ID
- 2021P000376
- Status last verified
- Nov 2024
- First submitted
- 17 Mar 2021
- Last updated
- 3 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Buspirone for the Treatment of Anxiety in Williams Syndrome
- ClinicalTrials.gov ID
- NCT04807517
- Acronym / sponsor ID
- 2021P000376
- Conditions
- Williams Syndrome, Anxiety
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Aug 2021 (actual)
- Primary completion
- 11 Sep 2023 (actual)
- Study completion
- 11 Sep 2023 (actual)
- First posted
- 19 Mar 2021 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Buspirone | Experimental | Drug: BuspironeSubjects 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. |
Who may qualify
- Ages
- 5 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
- 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.
- A Clinical Global Impression Severity Item score ≥ 4 (moderate) for anxiety symptoms at Screen and Baseline.
Key exclusion criteria (6 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BuspironeAll 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. | Drug | Buspirone |
Primary outcome
Mean 16-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported
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.
5 secondary outcomes
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)
Time frame: 16 weeks
Mean 16-Week Change in Child and Adolescent Symptom Inventory Anxiety-Modified Score
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robyn P Thom, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Buspirone in people with Williams Syndrome and Anxiety, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean 16-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score (time frame: Baseline, Week 4, Week 8, Week 12, Week 16; Change from Baseline to Week 16 reported). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2024.