Trial Outcomes & Findings for Buspirone Treatment of Anxiety in Williams Syndrome (NCT NCT04807517)

Last Updated: 2024-12-03

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

20 participants

Primary outcome timeframe

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

Results posted on

2024-12-03

Participant Flow

Participants were recruited between May 2021 and March 2023 through the Williams Syndrome Association and the Williams Syndrome Registry, as well as other specialty and primary care clinics. A recruitment letter was also sent to patients diagnosed with Williams Syndrome through the Mass General Brigham Patient Gateway secure online patient portal.

All 20 enrolled participants met inclusion criteria.

Participant milestones

Participant milestones
Measure	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. 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.
Overall Study STARTED	20
Overall Study Started Taking Medication After Baseline	19
Overall Study Remained in Study at Week 12	18
Overall Study Remained in Study at Week 16	18
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Buspirone Treatment of Anxiety in Williams Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Buspirone n=20 Participants 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. 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.
Age, Categorical <=18 years	14 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	17.4 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants

PRIMARY outcome

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

Population: All 20 participants contributed a baseline PARS 5-item total score to the analysis. Due to study discontinuation and a missing assessment, numbers of participants contributing post-baseline scores were 19 at week 4, 18 at week 8, 18 at week 12, and 18 at week 16.

Outcome measures

Outcome measures
Measure	Buspirone n=20 Participants 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. 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.
Mean 16-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score	-7.9 score on a scale Interval -10.0 to -5.9

SECONDARY outcome

Timeframe: 16 weeks

Population: Participants who completed the study

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.

Outcome measures

Outcome measures
Measure	Buspirone n=18 Participants 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. 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.
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)	1.00 Proportion of participants Interval 0.82 to 1.0

SECONDARY outcome

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

Population: All 20 participants contributed a baseline CASI modified score to the analysis . Due to study discontinuation and missing assessments, numbers of participants contributing post-baseline scores were 19 at week 4, 18 at week 8, 17 at week 12, and 18 at week 16.

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.

Outcome measures

Outcome measures
Measure	Buspirone n=20 Participants 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. 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.
Mean 16-Week Change in Child and Adolescent Symptom Inventory Anxiety-Modified Score	-8.9 score on a scale Interval -12.8 to -4.9

SECONDARY outcome

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

Population: All 20 participants contributed a baseline parent-report SCARED total score to the analysis . Due to study discontinuation and missing or incomplete assessments, numbers of participants contributing post-baseline parent-report scores were 19 at week 4, 18 at week 8, 17 at week 12, and 18 at week 16, and numbers contributing child-report scores were 9 at baseline, 8 at week 4, 10 at week 8, 7 at week 12, and 8 at week 16, with 10 contributing a score at either baseline or week 16.

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.

Outcome measures

Outcome measures
Measure	Buspirone n=20 Participants 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. 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.
Mean 16-Week Change in Screen for Childhood Anxiety Related Emotional Disorders Total Score Child/self-report form	-16.0 score on a scale Interval -28.1 to -3.9
Mean 16-Week Change in Screen for Childhood Anxiety Related Emotional Disorders Total Score Parent-report form	-9.3 score on a scale Interval -13.4 to -5.1

SECONDARY outcome

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

Population: All 20 participants contributed baseline ABC subscale scores to the analysis . Due to study discontinuation and missing assessments, numbers of participants contributing post-baseline scores were 19 at week 4, 18 at week 8, 17 at week 12, and 18 at week 16.

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.

Outcome measures

Outcome measures
Measure	Buspirone n=20 Participants 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. 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.
Mean 16-Week Change in Each Subscale of the Aberrant Behavior Checklist Irritability	-6.3 score on a scale Interval -10.3 to -2.4
Mean 16-Week Change in Each Subscale of the Aberrant Behavior Checklist Social withdrawal/lethargy	-3.6 score on a scale Interval -6.1 to -1.0
Mean 16-Week Change in Each Subscale of the Aberrant Behavior Checklist Stereotypy	-1.8 score on a scale Interval -3.0 to -0.6
Mean 16-Week Change in Each Subscale of the Aberrant Behavior Checklist Hyperactivity	-6.2 score on a scale Interval -9.4 to -2.9
Mean 16-Week Change in Each Subscale of the Aberrant Behavior Checklist Inappropriate speech	-0.8 score on a scale Interval -1.7 to 0.1

SECONDARY outcome

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

Population: All 20 participants contributed a baseline PSQI global score to the analysis . Due to study discontinuation and missing assessments, numbers of participants contributing post-baseline scores were 19 at week 4, 18 at week 8, 16 at week 12, and 17 at week 16.

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.

Outcome measures

Outcome measures
Measure	Buspirone n=20 Participants 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. 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.
Mean 16-Week Change in Pittsburgh Sleep Quality Index Global Score	-1.4 score on a scale Interval -2.3 to -0.5

Adverse Events

Buspirone

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Buspirone n=20 participants at risk 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. 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.
Gastrointestinal disorders Diarrhea	40.0% 8/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
General disorders Appetite decrease	35.0% 7/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Gastrointestinal disorders Stomach or abdominal discomfort	35.0% 7/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Infections and infestations Nasal congestion or cold	30.0% 6/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Gastrointestinal disorders Nausea	25.0% 5/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Gastrointestinal disorders Vomiting	25.0% 5/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Psychiatric disorders Sadness	25.0% 5/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Nervous system disorders Headache	20.0% 4/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Infections and infestations Flu or other respiratory problems	20.0% 4/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
General disorders Dry mouth	15.0% 3/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Psychiatric disorders Interrupted sleep/ other sleep problems	15.0% 3/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
General disorders Tiredness/fatigue	15.0% 3/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Gastrointestinal disorders Constipation	10.0% 2/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Psychiatric disorders Irritability	10.0% 2/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
General disorders Sedation/drowsiness	10.0% 2/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
General disorders Weakness	10.0% 2/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Nervous system disorders Dizziness/faintness	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Respiratory, thoracic and mediastinal disorders Asthmatic symptoms	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
General disorders Appetite increase	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Gastrointestinal disorders Indigestion	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Skin and subcutaneous tissue disorders Localized rash	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
General disorders Sweating	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Psychiatric disorders Change in speech	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Nervous system disorders Confusion	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Psychiatric disorders Disinhibition	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Psychiatric disorders Suicidal ideas	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
General disorders Fever	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Gastrointestinal disorders Acid reflux	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Nervous system disorders Ataxia	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Gastrointestinal disorders Belching	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Musculoskeletal and connective tissue disorders Hand pain	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Psychiatric disorders Lip picking	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Nervous system disorders Paresthesia	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Infections and infestations Pneumonia	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Musculoskeletal and connective tissue disorders Shoulder injury	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Psychiatric disorders Social withdrawal	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Nervous system disorders Stuttering	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.
Renal and urinary disorders Urinary tract infection	5.0% 1/20 • The earlier of 16 weeks or study discontinuation Adverse event data were collected via a structured side effect rating scale completed with the participant and their primary caregiver.

Additional Information

Lurie Center Research Manager

Massachusetts General Hospital Lurie Center for Autism

Phone: 781-860-1711

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place