Mirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Changes in lower esophageal sphincter pressures
研究概览
简要总结
This study evaluates whether a medication called mirabegron is better than placebo (sugar pill) in helping patients with achalasia swallow better. Each patient will receive either mirabegron or the placebo for 4 weeks followed by the opposite medication. Each patient will complete several surveys and undergo several tests to determine if the mirabegron is helping reduce the pressures in the esophagus (swallowing tube).
详细描述
Achalasia is characterized by incomplete or absent relaxation of the lower esophageal sphincter (LES) and loss of esophageal peristalsis which leads to dysphagia. Standard of care for achalasia includes endoscopic management (dilation and injection of injection of botulinum toxin) and surgery, however both of these options carry procedural risks, may lose efficacy over time and many patients are not appropriate candidates for these treatment options. Unfortunately, there are limited oral medications for patients with achalasia. Mirabegron is an oral beta-3 agonist currently FDA approved for overactive bladder that works by relaxing the bladder muscles. Beta-3 receptors have also been identified in the LES with stimulation leading to LES relaxation in preclinical studies. Through a proof of concept pilot study, the investigators aim to evaluate the effect of mirabegron in patients with achalasia via high resolution manometry and a validated dysphagia scale.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years old < Age < 75 years old with prior diagnosis of achalasia via manometry and/or radiographically
排除标准
- •< 18 years old or > 75 years old
- •History of hypertension not controlled on oral medications (blood pressure > 160/100 mm Hg)
- •No prior history of hypertension with a blood pressure > 160/100 mm Hg
- •History of bladder outlet obstruction
- •History of angioedema
- •Pregnant or breast-feeding women: Women between 18 and 40 years old who are enrolled in the study will be required to use a form of birth control during the study
- •Patients currently receiving certain medications (digoxin, warfarin, any overactive bladder medications, thioridazine, flecainide, propafenone, phosphodiesterase inhibitors)
- •Patients with prolonged QTc interval or risk factors to develop it:
- •Baseline QTc on EKG of > 450 milliseconds
- •History of additional risk factors for Torsades de Pointes (heart failure, family history of long QT syndrome)
- •Concomitant medications that prolong the QTc interval: ranolazine, sotalol, dofetilide, procainamide, disopyramide, propafenone, azole antifungals, fluoroquinolones, macrolide antibiotics, HIV antiretrovirals, chemotherapy, beta-2 agonists, tricyclic antidepressants, selective serotonin reuptake inhibitors
- •Prior surgeries for achalasia
- •< 2 months since last endoscopic botulinum toxin injection into LES or endoscopic dilation
- •Stage 4 Chronic kidney disease (severe renal impairment with GFR 15-29 ml/min), Stage 5 Chronic Kidney disease (GFR < 15 ml/min or on dialysis)
- •Childs Pugh B (moderate) or C (severe) Cirrhotic (hepatic impairment)
研究组 & 干预措施
Mirabegron
Patients will receive 50 mg of oral Mirabegron daily for 4 weeks and then switch to placebo by mouth daily for an additional 4 weeks.
干预措施: Mirabegron 50 MG (Drug)
Mirabegron
Patients will receive 50 mg of oral Mirabegron daily for 4 weeks and then switch to placebo by mouth daily for an additional 4 weeks.
干预措施: Placebo (Drug)
Placebo
Patients will receive placebo by mouth daily for 4 weeks and then switch to oral Mirabegron 50 mg daily for an additional 4 weeks.
干预措施: Mirabegron 50 MG (Drug)
Placebo
Patients will receive placebo by mouth daily for 4 weeks and then switch to oral Mirabegron 50 mg daily for an additional 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Changes in lower esophageal sphincter pressures
时间窗: Change in lower esophageal sphincter pressure from baseline after 4 weeks of placebo or Mirabegron
Evaluation of changes in lower esophageal sphincter pressures using high resolution manometry
次要结局
- Eckardt Achalasia Score (EAS)(Patients will complete the EAS on study day -14, 0, 7, 28, 42, 49, 70, 84. We will evaluate changes in patient's EAS between day 0 and all of these time points.)
研究者
Jeff GI
Dr Anthony J DiMarino, Chair, Division of Gastroenterology
Thomas Jefferson University