Clinical trial NCT03587142: Buspirone for Early Satiety and Symptoms of Gastroparesis
Official title: Buspirone for Early Satiety and Symptoms of Gastroparesis: A Multicenter, Randomized, Placebo-Controlled, Double-Masked Trial (BESST)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroparesis
Keywords: gastroparesis
early satiety
stomach
buspirone
5-HT 1a receptor agonist
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Texas Tech University Health Sciences Center, El Paso
name: Johns Hopkins University
name: Temple University
name: University of Louisville
name: Wake Forest University
name: Massachusetts General Hospital
First posted: 2018-07-16
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity
timeFrame: baseline and 4-weeks
Secondary outcomes:
measure: 4-Week Change in Stomach Fullness Symptom Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Excessive Fullness Symptom Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Inability to Finish a Normal-sized Meal Symptom Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Loss of Appetite Symptom Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Total Overall GCSI Symptom Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Nausea, Vomiting and Retching Symptoms Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Nausea Symptom Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Vomiting Symptom Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Bloating and Stomach Distention Symptoms Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Bloating Symptom Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Upper Abdominal Pain and Discomfort Symptoms Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Upper Abdominal Pain Symptom Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Gastroesophageal (GERD) Symptoms Severity
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Gastrointestinal Symptoms Rating Scale (GSRS) Global Score
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Participant's Rating of Symptom Relief
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Severity of Somatic Symptoms
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Depression
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Anxiety
timeFrame: baseline and 4-weeks
measure: 4-Week Change Overall Quality of Health Due to Gastroparesis Issues
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Overall Mental Quality of Life (QOL)
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Overall Physical Quality of Life (QOL)
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Gastric Retention
timeFrame: baseline and 4-weeks
measure: Change at 4-weeks in the Intragastric Meal Distribution (IMD)
timeFrame: baseline and 4-weeks
measure: Change From Baseline at 4-weeks in the Water Load Satiety Test (WLST)
timeFrame: baseline and 4-weeks
Other outcomes:
measure: 4-Week Change in Weight
timeFrame: baseline and 4-weeks
measure: 4-Week Cardiac Rhythm
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Aspartate Aminotransferase (ALT)
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Creatinine
timeFrame: baseline and 4-weeks
measure: 4-Week Change in Fasting Glucose
timeFrame: baseline and 4-weeks
measure: Assessment of Adverse Events Over 4-Weeks
timeFrame: over 4-weeks
measure: Assessment of the Severity of Adverse Events Over 4-Weeks
timeFrame: over 4-weeks
measure: Serious Adverse Events
timeFrame: over 4 weeks of treatment
measure: Total Number of Hospitalizations Over 4-weeks of Treatment
timeFrame: over the 4-weeks of the trial
measure: Adverse Events by Body Classification System by Treatment Group During the Trial
timeFrame: over 4-weeks of treatment
Locations:
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: El Paso
country: United States
facility: Texas Tech University Health Science Center
state: Texas
Study officials:
affiliation: Temple University Hospital, Philadelphia, PA
name: Henry P Parkman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Hospital, Baltimore, MD
name: Pankaj J Pasricha, MD
role: STUDY_CHAIR
References: