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TerminatedNCT03411252Updated Mar 24, 2021

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

An Early Phase 1 interventional study of Mirabegron 50 MG and Placebo in Achalasia, sponsored by Thomas Jefferson University. Terminated at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-03-24.

Sponsored by Thomas Jefferson University · Early Phase 1, Interventional, and Treatment

Why this study was terminated
inability to enroll
Phase
Early Phase 1
Study type
Interventional
Enrollment
5
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Achalasia

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03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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

Exclusion criteria

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)
04

Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
5 participants (actual)

Study arms

  • Experimental
    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.

    Drug: Mirabegron 50 MG · Drug: Placebo

  • Placebo comparator
    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.

    Drug: Mirabegron 50 MG · Drug: Placebo

Interventions

  • DrugMirabegron 50 MG

    Myrbetriq (Mirabegron) tablet

    Also known as: Myrbetriq

  • DrugPlacebo

    Sugar pill manufactured to mimic Mirabegron

    Also known as: Placebo (for Mirabegron)

05

What researchers measure

Primary outcomes

  1. Changes in lower esophageal sphincter pressures

    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 outcomes

  1. 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.

    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.

06

Study locations

1 site
  • Thomas Jefferson University
    Philadelphia, Pennsylvania 19107, United States
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03411252
Lead sponsor
Thomas Jefferson University
Collaborators
Astellas Pharma Inc
Responsible party
Jeff GI (Dr Anthony J DiMarino, Chair, Division of Gastroenterology, Thomas Jefferson University) — Principal investigator
First posted
Jan 26, 2018
Start date
Feb 15, 2018
Primary completion
Dec 15, 2019
Completion
Dec 15, 2019
Last update
Mar 24, 2021

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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