Mirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study

Achalasia Clinical Trial

Official title:

Mirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03411252
• Other study ID #: 17P.054
• Status: Terminated
• Phase: Early Phase 1
• Start date: February 15, 2018
• Est. completion date: December 15, 2019

Study information

• Verified date: March 2021
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: December 15, 2019
• Est. primary completion date: December 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18 years old < Age < 75 years old with prior diagnosis of achalasia via manometry and/or radiographically

Exclusion Criteria:

• < 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)

Related Conditions & MeSH terms

• Achalasia
• Esophageal Achalasia

Intervention

Drug:
• Mirabegron 50 MG
Myrbetriq (Mirabegron) tablet
• Placebo
Sugar pill manufactured to mimic Mirabegron

Locations

Country	Name	City	State
United States	Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Thomas Jefferson University	Astellas Pharma Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in lower esophageal sphincter pressures	Evaluation of changes in lower esophageal sphincter pressures using high resolution manometry	Change in lower esophageal sphincter pressure from baseline after 4 weeks of placebo or Mirabegron
Secondary	Eckardt Achalasia Score (EAS)	Patients will complete the Eckardt Achalasia score which is a simple written scale evaluating dysphagia, regurgitation, retrosternal pain and weight loss. Patients report their symptoms from a 0 to 3. Weight loss (0-none, 1: < 5 kg, 2: 5-10 kg, 3: > 10 kg), Dysphagia (0-none, 1-occasional, 2-daily, 3-each meal), Retrosternal pain (0-none, 1-occasional, 2-daily, 3-each meal), Regurgitation (0-none, 1-occasional, 2-daily, 3-each meal). The value for each of the 4 categories is added together to give the EAS. This EAS will be reported for each time point below. A higher score is consistent with worse achalasia and worse outcomes. A lower score is consistent with less severe achalasia and better outcomes. The total range is 0 (no symptoms) to 12 (severe symptoms). There are no subscales.	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.