Buspirone for Early Satiety and Symptoms of Gastroparesis (BESST)

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

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.

Study Overview

• Status: Completed
• Conditions: Gastroparesis
• Intervention / Treatment: Drug: Buspirone; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
  • Texas
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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 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 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 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
4-Week Change in Weight	This safety outcome is computed by subtracting the weight (kg) at baseline from the weight (kg) at 4-weeks	baseline and 4-weeks
4-Week Change in Creatinine	This safety outcome is computed by subtracting the baseline level of creatinine (mg/dL) from the 4-week level.	baseline and 4-weeks
4-Week Change in Fasting Glucose	This safety outcome is computed by subtracting the baseline level of glucose (mg/dL) from the 4-week level.	baseline and 4-weeks
4-Week Cardiac Rhythm	This safety outcome is computed from the results of an electrocardiogram (ECG) QTc interval at 4-weeks measured in milliseconds (msec).	baseline and 4-weeks
4-Week Change in Aspartate Aminotransferase (ALT)	This safety outcome is computed by subtracting the baseline level of Alanine Aminotransferase (ALT) (U/L) from the 4-week level.	baseline and 4-weeks
Assessment of Adverse Events Over 4-Weeks	This safety outcome is the frequency over the 4-weeks of the study of all reported adverse events using the v5.0 CTCAE classification system.	over 4-weeks
Assessment of the Severity of Adverse Events Over 4-Weeks	This safety outcome is the frequency over the 4-weeks of the study of all reported adverse events' severity grade as classified by the NCI's Common Terminology Criteria for Adverse Events (CTCAE v5.0). For the patient with 2 AE's, the AE with the maximum severity is reported.	over 4-weeks
Serious Adverse Events	Serious Adverse Event (SAE) defined by the FDA as an event meeting one or more of the following criteria; inpatient hospitalization or prolonged existing hospitalization; persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; jeopardized patient and required medical or surgical intervention to prevent a serious event; or congenital anomaly or birth defect.	over 4 weeks of treatment
Total Number of Hospitalizations Over 4-weeks of Treatment	Hospitalization events by treatment arm were reported on the Adverse Event Case-Report form at each visit and also at time of occurrence and tabulated at end of treatment visit for comparison between placebo and buspirone arms.	over the 4-weeks of the trial
Adverse Events by Body Classification System by Treatment Group During the Trial	Adverse events were reported on the Adverse Event Report form by the principal investigator at each clinic site using the CTCAE v5 classification system.	over 4-weeks of treatment

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: Johns Hopkins University; Massachusetts General Hospital; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Temple University; University of Louisville; Texas Tech University Health Sciences Center, El Paso; Wake Forest University
• Investigators: Principal Investigator: Henry P Parkman, MD, Temple University Hospital, Philadelphia, PA; Study Chair: Pankaj J Pasricha, MD, Johns Hopkins Hospital, Baltimore, MD

Publications and helpful links

Helpful Links

• Link to the Gastroparesis Clinical Research Consortium (GpCRC) web site Home page. There are some open-links for patients, such as Information for Patients.

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2019
• Primary Completion (Actual): April 15, 2022
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (Actual): July 16, 2018

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: stomach; gastroparesis; early satiety; buspirone; 5-HT 1a receptor agonist
• Additional Relevant MeSH Terms: Digestive System Diseases; Neurologic Manifestations; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Gastroparesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Anti-Anxiety Agents; Buspirone
• Other Study ID Numbers: 10- GpCRC3-BESST; U24DK074008 (U.S. NIH Grant/Contract); U01DK073983 (U.S. NIH Grant/Contract); U01DK112193 (U.S. NIH Grant/Contract); U01DK073975 (U.S. NIH Grant/Contract); U01DK074035 (U.S. NIH Grant/Contract); U01DK074007 (U.S. NIH Grant/Contract); U01DK073974 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study will comply with the NIH Data Sharing Policy. The data will be first de-identified so that no individual participant identifiers will be included in the dataset (no names, addresses, dates, comments, etc). If a characteristic is an extreme value for this population, then those values will be categorized into one frequency group. If a CSR has multiple versions, then all data will be recoded into the format of the most current form version. A random unique identification number will be substituted for the unique BESST identification number. If a clinical item was obtained from surveys with restrictions due to licensing, then that data will be excluded. The data will be shared in 2 stages: the first will be the analytic datasets to produce the primary outcome paper. For this dataset, the documentation will include analytic code. The full dataset by CSR will be provided in the second stage.
• IPD Sharing Time Frame: The analytic datasets to produce the primary result manuscript will be submitted within one year of publication of the primary result manuscript. The full clinical dataset for all Clinical Study Reports (CSRs) without proprietary restrictions will be submitted within 2 years of the primary result manuscript publication. This data will be available publicly indefinitely.
• IPD Sharing Access Criteria: An investigator interested in acquiring BESST study data should contact the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository at https://www.niddkrepository.org/search/study/ and apply to obtain the data required for their study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes