Back to resultsMirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study
Primary Purpose
Achalasia
Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Mirabegron 50 MG
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Achalasia
Eligibility Criteria
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)
Sites / Locations
- Thomas Jefferson University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Mirabegron
Placebo
Arm Description
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.
Patients will receive placebo by mouth daily for 4 weeks and then switch to oral Mirabegron 50 mg daily for an additional 4 weeks.
Outcomes
Primary Outcome Measures
Changes in lower esophageal sphincter pressures
Evaluation of changes in lower esophageal sphincter pressures using high resolution manometry
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT03411252
First Posted
December 11, 2017
Last Updated
March 22, 2021
Sponsor
Thomas Jefferson University
Collaborators
Astellas Pharma Inc
1. Study Identification
Unique Protocol Identification Number
NCT03411252
Brief Title
Mirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study
Official Title
Mirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
inability to enroll
Study Start Date
February 15, 2018 (Actual)
Primary Completion Date
December 15, 2019 (Actual)
Study Completion Date
December 15, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Thomas Jefferson University
Collaborators
Astellas Pharma Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Achalasia
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mirabegron
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive placebo by mouth daily for 4 weeks and then switch to oral Mirabegron 50 mg daily for an additional 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Mirabegron 50 MG
Other Intervention Name(s)
Myrbetriq
Intervention Description
Myrbetriq (Mirabegron) tablet
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo (for Mirabegron)
Intervention Description
Sugar pill manufactured to mimic Mirabegron
Primary Outcome Measure Information:
Title
Changes in lower esophageal sphincter pressures
Description
Evaluation of changes in lower esophageal sphincter pressures using high resolution manometry
Time Frame
Change in lower esophageal sphincter pressure from baseline after 4 weeks of placebo or Mirabegron
Secondary Outcome Measure Information:
Title
Eckardt Achalasia Score (EAS)
Description
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.
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Facility Information:
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Mirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study
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