BESST: Buspirone for Early Satiety and Symptoms of Gastroparesis

Sponsor

Johns Hopkins Bloomberg School of Public Health (Other)

Overall Status

Completed

CT.gov ID

NCT03587142

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Texas Tech University Health Sciences Center, El Paso (Other), Johns Hopkins University (Other), Temple University (Other), University of Louisville (Other), Wake Forest University (Other), Massachusetts General Hospital (Other)

Enrollment

Locations

Arms

32.1

Actual Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gastroparesis	Drug: Buspirone Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

96 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant, Care Provider, Investigator)

Masking Description:

Participants, all clinic staff and the investigators will be masked as to whether the participant is receiving buspirone or the placebo. The study drug will be over encapsulated in a size 0 gelatin capsule with partial filler to be identical to the placebo capsule, which contains only filler. The random treatment assignment will consist of a numbered study drug bottle; each bottle number will be unique and each participant will be assigned a specific bottle number, which is labelled: "Buspirone or placebo 10 mg." with directions. The randomization scheme will assign participants in randomly permuted blocks of assignments stratified by clinical center. The randomization plan will be prepared and administered centrally via a secure web application by the Scientific Data Research Center.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 27, 2019

Actual Primary Completion Date :

Apr 15, 2022

Actual Study Completion Date :

Apr 30, 2022

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity [baseline and 4-weeks]
The outcome is assessed using the self-reported postprandial fullness/early satiety subscore, 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.

Secondary Outcome Measures

4-Week Change in Total Overall GCSI Symptom Severity [baseline and 4-weeks]
The outcome is assessed using the self-reported total GCSI score, which is computed as the average of the 3 subscores on the GCSI survey: 3-item postprandial fullness/early satiety 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.
4-Week Change in Nausea, Vomiting and Retching Symptoms Severity [baseline and 4-weeks]
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 GCSI survey: nausea, retching, vomiting. 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.
4-Week Change in Bloating and Stomach Distention Symptoms Severity [baseline and 4-weeks]
The outcome is assessed using the self-reported bloating subscore, which is computed as the average of 2 scores for 2-items on the 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.
4-Week Change in Upper Abdominal Pain and Discomfort Symptoms Severity [baseline and 4-weeks]
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 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.
4-Week Change in Gastroesophageal (GERD) Symptoms Severity [baseline and 4-weeks]
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.
4-Week Change in Nausea Symptom Severity [baseline and 4-weeks]
The outcome is assessed using self-reported assessment of nausea severity in the prior 2-weeks using the 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.
4-Week Change in Vomiting Symptom Severity [baseline and 4-weeks]
The outcome is assessed using self-reported assessment of vomiting severity in the prior 2-weeks using the 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.
4-Week Change in Stomach Fullness Symptom Severity [baseline and 4-weeks]
The outcome is assessed using self-reported assessment of stomach fullness severity in the prior 2-weeks using the 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.
4-Week Change in Inability to Finish a Normal-sized Meal Symptom Severity [baseline and 4-weeks]
The outcome is assessed using self-reported assessment of inability to finish a normal-sized meal severity in the prior 2-weeks using the 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.
4-Week Change in Excessive Fullness Symptom Severity [baseline and 4-weeks]
The outcome is assessed using self-reported assessment of feeling excessively full after meals severity in the prior 2-weeks using the 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.
4-Week Change in Loss of Appetite Symptom Severity [baseline and 4-weeks]
The outcome is assessed using self-reported assessment of loss of appetite severity in the prior 2-weeks using the 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.
4-Week Change in Bloating Symptom Severity [baseline and 4-weeks]
The outcome is assessed using self-reported assessment of bloating severity in the prior 2-weeks using the 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.
4-Week Change in Upper Abdominal Pain Symptom Severity [baseline and 4-weeks]
The outcome is assessed using self-reported assessment of upper abdominal pain severity in the prior 2-weeks using the 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.
4-Week Change in Gastrointestinal Symptoms Rating Scale (GSRS) Global Score [baseline and 4-weeks]
The outcome is assessed using the self-reported GSRS total score which is computed as the mean of the 15 item scores on the 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.
4-Week Change in Participant's Rating of Symptom Relief [baseline and 4-weeks]
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.
4-Week Change Overall Quality of Health due to Gastroparesis Issues [baseline and 4-weeks]
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.
4-Week Change in Depression [baseline and 4-weeks]
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.
4-Week Change in Anxiety [baseline and 4-weeks]
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.
4-Week Change in Severity of Somatic Symptoms [baseline and 4-weeks]
The outcome is assessed using the self-reported Patient Health Questionnaire 15 Somatic Symptom Severity Scale (PHQ-15) total somatization score, calculated as the sum of 15-items, each scored from 0 (not bothered at all) to 3 (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.
4-Week Change in Overall Mental Quality of Life (QOL) [baseline and 4-weeks]
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.
4-Week Change in Overall Physical Quality of Life (QOL) [baseline and 4-weeks]
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.
4-Week Change in Gastric Retention [baseline and 4-weeks]
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.

Other Outcome Measures

4-Week Change in Weight [baseline and 4-weeks]
This safety outcome is computed by subtracting the weight (kg) at baseline from the weight (kg) at 4-weeks
4-Week Cardiac Rhythm [4-weeks]
This safety outcome is computed from the results of an electrocardiogram (ECG) at 4-weeks.
4-Week Change in aspartate aminotransferase (ALT) [baseline and 4-weeks]
This safety outcome is computed by subtracting the baseline level of ALT (U/L) from the 4-week level.
4-Week Change in Creatinine [baseline and 4-weeks]
This safety outcome is computed by subtracting the baseline level of creatinine (mg/dL) from the 4-week level.
4-Week Change in Fasting Glucose [baseline and 4-weeks]
This safety outcome is computed by subtracting the baseline level of glucose (mg/dL) from the 4-week level.
Assessment of Symptom Side Effects over 4-Weeks [over 4-weeks]
This safety outcome is the frequency over the 4-weeks of the study of symptom side effects as reported on the 9 questions of the Symptom Side Effects survey.
Assessment of Adverse Events over 4-Weeks [over 4-weeks]
This safety outcome is the frequency over the 4-weeks of the study of all reported adverse events.
Assessment of the Severity of Adverse Events over 4-Weeks [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Louisville	Louisville	Kentucky	United States	40202
2	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
3	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
4	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
5	Temple University	Philadelphia	Pennsylvania	United States	19140
6	Texas Tech University Health Science Center	El Paso	Texas	United States	79905

Sponsors and Collaborators

Johns Hopkins Bloomberg School of Public Health
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Texas Tech University Health Sciences Center, El Paso
Johns Hopkins University
Temple University
University of Louisville
Wake Forest University
Massachusetts General Hospital

Investigators

Principal Investigator: Henry P Parkman, MD, Temple University Hospital, Philadelphia, PA
Study Chair: Pankaj J Pasricha, MD, Johns Hopkins Hospital, Baltimore, MD