AchalasiaEarly Phase 1NCT03411252
Mirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study
A Early Phase 1 study testing Mirabegron 50 MG in people with Achalasia, run by Thomas Jefferson University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Achalasia
- What is being tested?
- Mirabegron 50 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2018to 15 Dec 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years old < Age < 75 years old with prior diagnosis of achalasia via manometry and/or radiographically
Who cannot join
- < 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
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
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.
- Conditions
- Achalasia
- Being tested
- Mirabegron 50 MG, Placebo
- Medical subject headings
- Esophageal Achalasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mirabegron 50 MGDrug
Also called Myrbetriq
Myrbetriq (Mirabegron) tablet
PlaceboDrug
Also called Placebo (for Mirabegron)
Sugar pill manufactured to mimic Mirabegron
| Study group | Role | What they receive |
|---|---|---|
| Mirabegron | Experimental | 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. Receives: Drug: Mirabegron 50 MG; Drug: Placebo |
| Placebo | Placebo comparator | Patients will receive placebo by mouth daily for 4 weeks and then switch to oral Mirabegron 50 mg daily for an additional 4 weeks. Receives: Drug: Mirabegron 50 MG; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in lower esophageal sphincter pressures
Evaluation of changes in lower esophageal sphincter pressures using high resolution manometry
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start15 Feb 2018
- Primary completion15 Dec 2019
- Study completion15 Dec 2019
Why it stopped: inability to enroll
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AchalasiaStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc
- Responsible party
- Principal investigator, Jeff GI, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03411252
- Sponsor's protocol ID
- 17P.054
- Status last verified
- Mar 2021
- First submitted
- 11 Dec 2017
- Last updated
- 24 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study
- ClinicalTrials.gov ID
- NCT03411252
- Acronym / sponsor ID
- 17P.054
- Conditions
- Achalasia
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: inability to enroll
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc
- Study start
- 15 Feb 2018 (actual)
- Primary completion
- 15 Dec 2019 (actual)
- Study completion
- 15 Dec 2019 (actual)
- First posted
- 26 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mirabegron | Experimental | Drug: Mirabegron 50 MG, Drug: PlaceboPatients will receive 50 mg of oral Mirabegron daily for 4 weeks and then switch to placebo by mouth daily for an additional 4 weeks. |
| Placebo | Placebo comparator | Drug: Mirabegron 50 MG, Drug: PlaceboPatients will receive placebo by mouth daily for 4 weeks and then switch to oral Mirabegron 50 mg daily for an additional 4 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 18 years old < Age < 75 years old with prior diagnosis of achalasia via manometry and/or radiographically
Key exclusion criteria (15 listed)
- < 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mirabegron 50 MGAlso: MyrbetriqMyrbetriq (Mirabegron) tablet | Drug | Mirabegron, Placebo |
| PlaceboAlso: Placebo (for Mirabegron)Sugar pill manufactured to mimic Mirabegron | Drug | Mirabegron, Placebo |
Primary outcome
Changes in lower esophageal sphincter pressures
Time frame: 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
1 secondary outcome
Eckardt Achalasia Score (EAS)
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.
Results and safety
The study was stopped early (reason given: inability to enroll). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2021.
- Individual participant dataSharing planned: No
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Achalasia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Mirabegron 50 MG in people with Achalasia, run by Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: inability to enroll). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in lower esophageal sphincter pressures (time frame: Change in lower esophageal sphincter pressure from baseline after 4 weeks of placebo or Mirabegron). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2021.