Buspirone for Early Satiety and Symptoms of Gastroparesis

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: June 30, 2021

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.

Interventions

  • Drug: Buspirone
    • Buspirone tablet
  • Drug: Placebo
    • “Sugar” pill manufactured to mimic buspirone 10 mg tablet

Arms, Groups and Cohorts

  • Active Comparator: Buspirone
    • Buspirone HCl 10 mg capsule orally three times daily, 30 minutes before each meal, for 4-weeks
  • Placebo Comparator: Placebo
    • Placebo capsule orally three times daily, 30 minutes before each meal, for 4-weeks; manufactured to look identical to buspirone capsule

Clinical Trial Outcome Measures

Primary Measures

  • 4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity
    • Time Frame: 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 Measures

  • 4-Week Change in Total Overall GCSI Symptom Severity
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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)
    • Time Frame: 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)
    • Time Frame: 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
    • Time Frame: 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.

Participating in This Clinical Trial

Inclusion Criteria

  • Age 18 to 75 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Henry P Parkman, MD, Principal Investigator, Temple University Hospital, Philadelphia, PA
    • Pankaj J Pasricha, MD, Study Chair, Johns Hopkins Hospital, Baltimore, MD
  • Overall Contact(s)
    • SDRC Principal Investigator James /Tonascia, PhD, 410-955-3704, jtonasc1@jhu.edu

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