Buspirone for Early Satiety and Symptoms of Gastroparesis

Study Overview
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Brief Summary
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This study evaluates whether the study medication, buspirone, an antianxiety drug, improves the symptoms of gastroparesis in patients with gastroparesis symptoms and at least moderately severe symptoms of fullness and/or inability to eat a full meal. Half the patients will receive buspirone and half the patients will receive a placebo.

Detailed Description
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This is a multi-center, randomized, double-masked, placebo-controlled, parallel treatment groups phase 2 trial to determine the effect of buspirone, a 5-hydroxytryptamine (5-HT) 1a receptor agonist, on early satiety and postprandial fullness in participants with symptoms of gastroparesis and with at least moderately severe symptoms of early satiety and/or postprandial fullness. After enrollment, participants aged 18-75 years will be treated with buspirone (10 mg three times per day) or a matching placebo for 4 weeks, followed by a 2-week post-treatment washout period. The primary outcome for the study is 4-week change (week 4 minus baseline) in the 4-item postprandial fullness/early satiety subscore (higher scores indicate worse symptoms) from the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) Gastroparesis Cardinal Symptom Index (GCSI). We hypothesize that buspirone treatment will improve symptoms of postprandial fullness/early satiety compared to treatment with placebo, as indicated by a lower (smaller, more negative) 4-week change in the postprandial fullness/early satiety subscore in the buspirone arm compared to the placebo arm; change for a participant will be calculated as subscore at 4-weeks minus subscore at baseline.

Official Title
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Buspirone for Early Satiety and Symptoms of Gastroparesis: A Multicenter, Randomized, Placebo-Controlled, Double-Masked Trial (BESST)

Conditions
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Gastroparesis

Intervention / Treatment
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* Drug: Buspirone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 85 years of age at initial screening interview Symptoms compatible with gastroparesis or other functional gastric disorder for at least 3 months (does not have to be contiguous) prior to initial screening interview Diagnosis of either diabetic or idiopathic gastroparesis Delayed or normal gastric emptying retention on screening 4-hour Gastric Emptying Scintigraphy test Symptoms of gastroparesis measured by the 9-item PAGI-SYM Gastroparesis Cardinal Symptom Index (GCSI) total score > 2.0 at enrollment Symptomatic with postprandial fullness/early satiety severity at enrollment using the PAGI-SYM GCSI post-prandial fullness/early satiety subscore ≥ 3 Upper endoscopy or upper GI series without ulcers or mass lesions in the 2 years prior to enrollment Exclusion Criteria: Post-surgical gastroparesis, including prior pyloromyotomy, pyloric resection, vagotomy, bariatric surgery or post-Nissen fundoplication Another active disorder which could explain symptoms in the opinion of the investigator Concurrent use of opiate narcotic analgesics more than 3 days per week Significant hepatic injury as defined by alanine aminotransferase (ALT) elevation of greater than twice the Upper Limit of Normal (ULN) or a Child-Pugh score of 10 or greater Significant renal impairment as defined by serum creatinine > 3.0 Uncontrolled diabetes defined as HbA1c (%) of 10% or more within 60 days of enrollment Allergy to buspirone Concurrent or prior use (within 30 days) of monoamine oxidase (MAO) inhibitors Concurrent or prior use (within 30 days) of benzodiazepines Concurrent or prior use (within 30 days) of buspirone, warfarin, haloperidol, and drugs to treat seizures (e.g., phenytoin and carbamazepine) Women breast feeding or known to be pregnant Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study Failure to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: BESST is a multi-center, randomized, placebo-controlled, double-masked, parallel treatment groups phase 2 trial with half the participants receiving the study drug, buspirone, and half receiving the placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Buspirone<br>Buspirone HCl 10 mg capsule orally three times daily, 30 minutes before each meal, for 4-weeks | Drug: Buspirone<br>* Buspirone tablet<br>* Other names: Vanspar;|
| Placebo Comparator: Placebo<br>Placebo capsule orally three times daily, 30 minutes before each meal, for 4-weeks; manufactured to look identical to buspirone capsule | Drug: Placebo<br>* Sugar pill manufactured to mimic buspirone 10 mg tablet<br>* Other names: Placebo (for buspirone);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity | The outcome is assessed using the self-reported early satiety/postprandial fullness subscore (ES/PPF), which is computed as the average of 4 scores for 4-items on the Gastroparesis Cardinal Symptom Index (GCSI) survey: stomach fullness, inability to finish a normal-sized meal, feeling excessively full after meals, and loss of appetite. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore. | baseline and 4-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4-Week Change in Stomach Fullness Symptom Severity | The outcome is assessed using self-reported assessment of stomach fullness severity in the prior 2-weeks using the Gastroparesis Cardinal Symptoms Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. | baseline and 4-weeks | 
| 4-Week Change in Excessive Fullness Symptom Severity | The outcome is assessed using self-reported assessment of feeling excessively full after meals severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. | baseline and 4-weeks | 
| 4-Week Change in Inability to Finish a Normal-sized Meal Symptom Severity | The outcome is assessed using self-reported assessment of inability to finish a normal-sized meal severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. | baseline and 4-weeks | 
| 4-Week Change in Loss of Appetite Symptom Severity | The outcome is assessed using self-reported assessment of loss of appetite severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. | baseline and 4-weeks | 
| 4-Week Change in Total Overall GCSI Symptom Severity | The outcome is assessed using the self-reported Gastroparesis Cardinal Symptom Index (GCSI) total score, which is computed as the average of the 3 subscores on the GCSI survey: 3-item early satiety/postprandial fullness subscore, the nausea/vomiting subscore (average of 3-items: nausea, retching, vomiting), and bloating subscore (average of 2-items: bloating, stomach visibly larger). Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the total score ranges from 0 to 5. The change is computed as the total score at 4-weeks minus the baseline total score. A negative change indicates improved symptoms. | baseline and 4-weeks | 
| 4-Week Change in Nausea, Vomiting and Retching Symptoms Severity | The outcome is assessed using the self-reported nausea/vomiting subscore, which is computed as the average of 3 scores for 3-items on the Gastrointestinal Cardinal Symptom Index (GCSI) survey: nausea, retching, vomiting. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks. The change is computed as the subscore at 4-weeks minus the baseline subscore. Negative change indicates improvement in symptoms. | baseline and 4-weeks | 
| 4-Week Change in Nausea Symptom Severity | The outcome is assessed using self-reported assessment of nausea severity item from the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. | baseline and 4-weeks | 
| 4-Week Change in Vomiting Symptom Severity | The outcome is assessed using self-reported assessment of vomiting severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates improvement in vomiting severity. | baseline and 4-weeks | 
| 4-Week Change in Bloating and Stomach Distention Symptoms Severity | The outcome is assessed using the self-reported bloating subscore, which is computed as the average of 2 scores for 2-items on the Gastroparesis Cardinal Symptom Index (GCSI) survey: bloating, stomach visibly larger. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore. A negative value for change indicates improvement in symptoms. | baseline and 4-weeks | 
| 4-Week Change in Bloating Symptom Severity | The outcome is assessed using self-reported assessment of bloating severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. | baseline and 4-weeks | 
| 4-Week Change in Upper Abdominal Pain and Discomfort Symptoms Severity | The outcome is assessed using the self-reported upper abdominal pain subscore, which is computed as the average of 2 scores for 2-items on the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) survey: upper abdominal pain, upper abdominal discomfort. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore. | baseline and 4-weeks | 
| 4-Week Change in Upper Abdominal Pain Symptom Severity | The outcome is assessed using self-reported assessment of upper abdominal pain severity in the prior 2-weeks using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. | baseline and 4-weeks | 
| 4-Week Change in Gastroesophageal (GERD) Symptoms Severity | The outcome is assessed using the self-reported GERD subscore, which is computed as the average of 7 scores for 7-items on the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) survey: heartburn during the day, heartburn when lying down, feeling of discomfort inside chest during the day, feeling of discomfort inside chest during sleep, regurgitation or reflux during the day, regurgitation when lying down, bitter, acid or sour taste in mouth. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore. | baseline and 4-weeks | 
| 4-Week Change in Gastrointestinal Symptoms Rating Scale (GSRS) Global Score | The outcome is assessed using the self-reported GSRS total score which is computed as the mean of the 15 item scores on the Gastrointestinal Symptom Rating Scale (GSRS) survey. Each item is scored from 1 (no discomfort) to 7 (very severe discomfort) of the symptom in the past week. The change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. | baseline and 4-weeks | 
| 4-Week Change in Participant's Rating of Symptom Relief | The outcome is assessed using the participant-rated Clinical Patient Grading Assessment Scale (CPGAS) score which is scored from -3 (very considerably worse) to 3 (completely better) in the past week compared to the way the participant usually feels. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates patient feeling better. | baseline and 4-weeks | 
| 4-Week Change in Severity of Somatic Symptoms | The outcome is assessed using the self-reported Patient Health Questionnaire 15 Somatic Symptom Severity Scale (PHQ-15) total somatization score (ranges from 0 -30, with 30 being most bothered by symptoms in prior 4-weeks), calculated as the sum of 15-items, each scored from 0 (not bothered at all) to 2 (bothered a lot) by somatic symptoms in the prior 4-weeks. The change is computed as the score at 4-weeks minus the baseline score. A negative change indicates being less bothered by the symptoms. | baseline and 4-weeks | 
| 4-Week Change in Depression | The outcome is assessed using the self-reported Hospital Anxiety and Depression Scale (HADS) depression subscore, calculated as the sum of 7 items, each scored from 0 (not at all) to 3 (most of the time). The change is computed as the subscore at 4-weeks minus the baseline subscore. A negative change indicates reduced depression. | baseline and 4-weeks | 
| 4-Week Change in Anxiety | The outcome is assessed using the self-reported Hospital Anxiety and Depression Scale (HADS) anxiety subscore, calculated as the sum of 7-items, each scored from 0 (not at all) to 3 (most of the time). The change is computed as the subscore at 4-weeks minus the baseline subscore. A negative change indicates reduced anxiety at 4-weeks. | baseline and 4-weeks | 
| 4-Week Change Overall Quality of Health Due to Gastroparesis Issues | The outcome is assessed using the self-reported Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) total score which comprises 30 items scored from 0 (none of the time) to 5 (all of the time) the participant's QOL has been affected by their gastrointestinal issues in the prior two weeks. The total score is the mean of the 5 subscale scores and ranges from 0 (lowest QOL) to 5 (highest QOL) in past 2-weeks. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates improved QOL. | baseline and 4-weeks | 
| 4-Week Change in Overall Mental Quality of Life (QOL) | The outcome is assessed using the self-reported 36-item Short Form Health Survey (SF-36v2) mental health QOL component score. The score ranges from 0 (poorest) to 100 (highest) QOL. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates improved mental QOL. | baseline and 4-weeks | 
| 4-Week Change in Overall Physical Quality of Life (QOL) | The outcome is assessed using the self-reported 36-item Short Form Health Survey (SF-36v2) physical health QOL component score. The score ranges from 0 (poorest) to 100 (highest) QOL. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates improved Physical QOL. | baseline and 4-weeks | 
| 4-Week Change in Gastric Retention | The outcome is assessed using the percent of gastric retention at 4-hours from the Gastric Emptying Scintigraphy (GES) test. The change is computed as the percent retention at 4-weeks minus the baseline percent retention. % retention is the amount of food remaining in the stomach at 4-hours of the GES test and ranges from 0% (no food) to 100% (all of the food). | baseline and 4-weeks | 
| Change at 4-weeks in the Intragastric Meal Distribution (IMD) | The Intragastric meal distribution (IMD) is assessed at baseline and 4-weeks during the Gastric Emptying Scintigraphy Test. The ratio of gastric counts of the meal in the proximal stomach to the distal stomach is used to compute the Intragastric meal distribution (IMD) which can be used as an indirect measure of Fundic Accommodation. | baseline and 4-weeks | 
| Change From Baseline at 4-weeks in the Water Load Satiety Test (WLST) | The Water Load Satiety Test (WLST) is the amount of water a patient can consume until full in 5 minutes. The volume of water is recorded. The change is computed as the volume of water ingested at baseline subtracted from the amount of water ingested at 4-weeks. A positive change indicates that the patient can ingest more water at 4-weeks than at baseline. | baseline and 4-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastroparesis, early satiety, stomach, buspirone, 5-HT 1a receptor agonist