Buspirone for Early Satiety and Symptoms of Gastroparesis: A Multicenter, Randomized, Placebo-Controlled, Double-Masked Trial (BESST)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 6
- 主要终点
- 4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Buspirone
Buspirone HCl 10 mg capsule orally three times daily, 30 minutes before each meal, for 4-weeks
干预措施: Buspirone (Drug)
Placebo
Placebo capsule orally three times daily, 30 minutes before each meal, for 4-weeks; manufactured to look identical to buspirone capsule
干预措施: Placebo (Drug)
结局指标
主要结局
4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity
时间窗: baseline and 4-weeks
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.
次要结局
- 4-Week Change in Stomach Fullness Symptom Severity(baseline and 4-weeks)
- 4-Week Change Overall Quality of Health Due to Gastroparesis Issues(baseline and 4-weeks)
- 4-Week Change in Excessive Fullness Symptom Severity(baseline and 4-weeks)
- 4-Week Change in Vomiting Symptom Severity(baseline and 4-weeks)
- 4-Week Change in Bloating and Stomach Distention Symptoms Severity(baseline and 4-weeks)
- 4-Week Change in Inability to Finish a Normal-sized Meal Symptom Severity(baseline and 4-weeks)
- 4-Week Change in Loss of Appetite Symptom Severity(baseline and 4-weeks)
- 4-Week Change in Bloating Symptom Severity(baseline and 4-weeks)
- 4-Week Change in Upper Abdominal Pain and Discomfort Symptoms Severity(baseline and 4-weeks)
- 4-Week Change in Total Overall GCSI Symptom Severity(baseline and 4-weeks)
- 4-Week Change in Nausea, Vomiting and Retching Symptoms Severity(baseline and 4-weeks)
- 4-Week Change in Nausea Symptom Severity(baseline and 4-weeks)
- 4-Week Change in Upper Abdominal Pain Symptom Severity(baseline and 4-weeks)
- 4-Week Change in Gastroesophageal (GERD) Symptoms Severity(baseline and 4-weeks)
- 4-Week Change in Gastrointestinal Symptoms Rating Scale (GSRS) Global Score(baseline and 4-weeks)
- 4-Week Change in Participant's Rating of Symptom Relief(baseline and 4-weeks)
- 4-Week Change in Severity of Somatic Symptoms(baseline and 4-weeks)
- 4-Week Change in Depression(baseline and 4-weeks)
- 4-Week Change in Anxiety(baseline and 4-weeks)
- 4-Week Change in Overall Mental Quality of Life (QOL)(baseline and 4-weeks)
- 4-Week Change in Gastric Retention(baseline and 4-weeks)
- Change at 4-weeks in the Intragastric Meal Distribution (IMD)(baseline and 4-weeks)
- 4-Week Change in Overall Physical Quality of Life (QOL)(baseline and 4-weeks)
- Change From Baseline at 4-weeks in the Water Load Satiety Test (WLST)(baseline and 4-weeks)