Esophageal AchalasiaNCT02663206
Peroral Endoscopic Myotomy Versus Botulinum Toxin Injection in Spastic Esophageal Disorders
A study testing peroral endoscopic myotomy and Botulinum toxin injection in people with Esophageal Achalasia and Esophageal Spasm, Diffuse, run by Johns Hopkins University at 1 site in United States.
Trial summary
To compare the efficacy of peroral endoscopic myotomy and Botulinum toxin injection in spastic esophageal disorders. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Esophageal Achalasia, Esophageal Spasm, Diffuse, Esophageal Motility Disorders
- What is being tested?
- peroral endoscopic myotomy and Botulinum toxin injection
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to Jul 2020
- Phase
- Interventional
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients age 18 - 80 years old.
- Spastic disorders of the esophagus include spastic (type III) achalasia, distal esophageal spasm (DES), and hypercontractile (jackhammer) esophagus via high resolution esophageal manometry (HRM) 2.
- DES is characterized by normal esophagogastric junction relaxation (integrated relaxation pressure [IRP] <15 mm Hg) and ≥ 20% premature contractions.
- Spastic achalasia is defined as impaired EGJ relaxation (IRP ≥15 mm Hg) associated with ≥ 20% premature contractions.
- The diagnosis of jackhammer esophagus is defined as at least 1 swallow with a distal contractile integral (DCI) greater than 8000 mm Hg- s- cm.
- At least 6 months of symptoms (chest pain, dysphagia, regurgitation and/or weight loss) with no adequate response or intolerance to medical therapy including nitrates and/or calcium channel blockers.
- Overall symptoms score (Eckardt score) > 3
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Diagnosis of spastic esophageal disorder was not confirmed by HRM testing.
- Previous surgery of the esophagus or stomach
- Previous BTX injection at the esophagogastric junction (EGJ) or LES.
- Active severe esophagitis
- Large lower esophageal diverticula
- Large > 3cm hiatal hernia
Show all 13Show fewer
- Megaesophagus (> 6 cm)
- Sigmoid esophagus
- Known gastroesophageal malignancy
- Inability to tolerate sedated upper endoscopy due to cardiopulmonary instability, severe pulmonary disease or other contraindication to endoscopy
- Cirrhosis with portal hypertension, varices, and/or ascites
- Uncorrectable coagulopathy defined by prothrombin time < 50% of control; partial thromboplastin time (PTT) > 50 sec, or international normalized ratio (INR) > 1.5), on chronic anticoagulation, or platelet count <75,000.
- Pregnant or breastfeeding women (all women of child-bearing age will undergo urine pregnancy testing)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Peroral Endoscopic Myotomy Versus Botulinum Toxin Injection in the Treatment of Medical Refractory Spastic Esophageal Disorders
To compare the efficacy of peroral endoscopic myotomy and Botulinum toxin injection in spastic esophageal disorders.
Read the detailed description
Spastic disorders of the esophagus encompass hyperactive conditions of the esophagus due to either abnormal premature contractions or extreme vigor. In the current iteration of the Chicago classification, spastic esophageal disorders include spastic (type III) achalasia, diffuse esophageal spasm (DES), and hypercontractile (jackhammer) esophagus. Management of these spastic esophageal disorders is challenging and not clearly defined. Several medical therapies have been suggested and include acid suppression, nitrates, muscle relaxants, and visceral analgesics. For those who fail to response to medical therapy, the treatment options are limited.
Botulinum toxin (BTX) injection is an effective therapeutic option for spastic esophageal disorders, however many patients experience symptoms relapse with this treatment requiring repeated injections.
Heller myotomy is a surgical option for patients with esophageal spastic disorders. As compared to other types of achalasia, the response rate to surgical myotomy was lower in patient with spastic achalasia. The theoretical reason for this is that the disease involves not only the lower esophageal sphincter (LES) but also the esophageal body. Given data to suggest that surgical myotomy may be effective in treating patients with spastic esophageal disorders, peroral endoscopic myotomy (POEM), which is a less invasive treatment modality, has recently been studied for these difficult-to-treat patients. An initial study reported high success rate of POEM for severe spastic esophageal disorders. The response rate as defined by Eckardt score to ≤ 3 was 96% in spastic achalasia, 100% in DES and 70% in those with Jackhammer esophagus after a median follow-up of 234 days in a largest case series of medically refractory spastic esophageal disorders.
To date, the optimal treatment for patients with severe symptomatic esophageal spastic disorders who fail medical therapy is unclear. Here, investigators aim to compare POEM and BTX injection in a randomized design.
To compare the efficacy of peroral endoscopic myotomy and Botulinum toxin injection in spastic esophageal disorders.
- Being tested
- peroral endoscopic myotomy, Botulinum toxin injection
- Keywords
- spastic esophageal disorders, achalasia, diffuse esophageal spasm, hypercontractile (jackhammer) esophagus, Botulinum toxin injection, peroral endoscopic myotomy
- Medical subject headings
- Esophageal Achalasia, Esophageal Spasm, Diffuse, Esophageal Motility Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
peroral endoscopic myotomyProcedure or surgery
peroral endoscopic myotomy
Botulinum toxin injectionProcedure or surgery
endoscopic Botulinum toxin (BTX) injection at lower esophagus
| Study group | Role | What they receive |
|---|---|---|
| Botulinum toxin injection | Other | Drug/Device: Botulinum toxin injection; Endoscopic Botulinum toxin (BTX) injection at lower esophagus; Upper endoscopy with Botulinum toxin injection.
The procedure will be performed as an outpatient basis by an endoscopist. Sedation can be in form of conscious sedation, monitored anesthesia care or general anesthesia. An upper endoscope will be inserted into the patient's mouth and advanced into lower esophagus. Botulinum toxin (Botox@) 100 units 8-10 (25 units/mL) will be injected in 1-ml portion in each of four quadrants about 1 cm above the Z-line (the LES region).
* At 1 month follow-up, patients who do not response to the first botox injection (Eckardt score > 3) will receive the second botox injection.
* At 3-month follow-up, POEM will be offered as a rescue therapy to both non-responders (Eckardt score > 3 at 3-month follow-up after the procedure) and relapsers (Eckardt score ≤ 3 at 3-month follow-up but becomes > 3 during the follow-up) Receives: Procedure: Botulinum toxin injection |
| peroral endoscopic myotomy | Other | Procedure/Surgery: peroral endoscopic myotomy.
The procedure will be performed by an endoscopist (gastroenterologist or surgeon). General anesthesia will be started and upper endoscope will be inserted into the patient's mouth and advanced into the stomach. Endoscopic myotomy will be performed. Mucosal entry will then be closed using endoscopic clips or endoscopic suturing.
All patients will recover from their procedures according to standard practice. They will remain nothing per oral (NPO) the night after the procedure and started on intravenous proton pump inhibitors. A gastrografin esophagram will be obtained the next day and if no evidence of leak, the diet will be advanced to a soft diet for two weeks. The patients will be evaluated by study coordinator/PI on a daily basis during their hospitalization. Receives: Procedure: peroral endoscopic myotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Eckardt score
symptoms scores
Measured: 3-month
Secondary outcomes (5)
Eckardt score
Measured: 1-year
changes in individual symptom scores
Each symptoms scores that are used to calculated Eckardt score
Measured: 3 months and 12 months
changes in esophageal manometry
Measured: 3 months
rate of complications
Measured: 3 months and 12 months
quality of life scores
Measured: 3 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2016 (estimated)
- Study startSep 2016
- Primary completionJul 2020 (estimated)
- Study completionJul 2020 (estimated)
Why it stopped: Eligible candidate for recruitment was not found
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal AchalasiaStudies of the same condition, open and under way.
- More trials run by Johns Hopkins 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mouen A Khashab, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02663206
- Sponsor's protocol ID
- IRB00049663
- Status last verified
- Jan 2018
- First submitted
- 5 Jan 2016
- Last updated
- 12 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peroral Endoscopic Myotomy Versus Botulinum Toxin Injection in the Treatment of Medical Refractory Spastic Esophageal Disorders
- ClinicalTrials.gov ID
- NCT02663206
- Acronym / sponsor ID
- IRB00049663
- Keywords
- spastic esophageal disorders, achalasia, diffuse esophageal spasm, hypercontractile (jackhammer) esophagus, Botulinum toxin injection, peroral endoscopic myotomy
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Eligible candidate for recruitment was not found
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2020 (estimated)
- First posted
- 26 Jan 2016 (estimated)
- 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.
To compare the efficacy of peroral endoscopic myotomy and Botulinum toxin injection in spastic esophageal disorders.
Detailed description
Spastic disorders of the esophagus encompass hyperactive conditions of the esophagus due to either abnormal premature contractions or extreme vigor. In the current iteration of the Chicago classification, spastic esophageal disorders include spastic (type III) achalasia, diffuse esophageal spasm (DES), and hypercontractile (jackhammer) esophagus. Management of these spastic esophageal disorders is challenging and not clearly defined. Several medical therapies have been suggested and include acid suppression, nitrates, muscle relaxants, and visceral analgesics. For those who fail to response to medical therapy, the treatment options are limited.
Botulinum toxin (BTX) injection is an effective therapeutic option for spastic esophageal disorders, however many patients experience symptoms relapse with this treatment requiring repeated injections.
Heller myotomy is a surgical option for patients with esophageal spastic disorders. As compared to other types of achalasia, the response rate to surgical myotomy was lower in patient with spastic achalasia. The theoretical reason for this is that the disease involves not only the lower esophageal sphincter (LES) but also the esophageal body. Given data to suggest that surgical myotomy may be effective in treating patients with spastic esophageal disorders, peroral endoscopic myotomy (POEM), which is a less invasive treatment modality, has recently been studied for these difficult-to-treat patients. An initial study reported high success rate of POEM for severe spastic esophageal disorders. The response rate as defined by Eckardt score to ≤ 3 was 96% in spastic achalasia, 100% in DES and 70% in those with Jackhammer esophagus after a median follow-up of 234 days in a largest case series of medically refractory spastic esophageal disorders.
To date, the optimal treatment for patients with severe symptomatic esophageal spastic disorders who fail medical therapy is unclear. Here, investigators aim to compare POEM and BTX injection in a randomized design.
To compare the efficacy of peroral endoscopic myotomy and Botulinum toxin injection in spastic esophageal disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Botulinum toxin injection | Other | Procedure: Botulinum toxin injectionDrug/Device: Botulinum toxin injection; Endoscopic Botulinum toxin (BTX) injection at lower esophagus; Upper endoscopy with Botulinum toxin injection. The procedure will be performed as an outpatient basis by an endoscopist. Sedation can be in form of conscious sedation, monitored anesthesia care or general anesthesia. An upper endoscope will be inserted into the patient's mouth and advanced into lower esophagus. Botulinum toxin (Botox@) 100 units 8-10 (25 units/mL) will be injected in 1-ml portion in each of four quadrants about 1 cm above the Z-line (the LES region). * At 1 month follow-up, patients who do not response to the first botox injection (Eckardt score > 3) will receive the second botox injection. * At 3-month follow-up, POEM will be offered as a rescue therapy to both non-responders (Eckardt score > 3 at 3-month follow-up after the procedure) and relapsers (Eckardt score ≤ 3 at 3-month follow-up but becomes > 3 during the follow-up) |
| peroral endoscopic myotomy | Other | Procedure: peroral endoscopic myotomyProcedure/Surgery: peroral endoscopic myotomy. The procedure will be performed by an endoscopist (gastroenterologist or surgeon). General anesthesia will be started and upper endoscope will be inserted into the patient's mouth and advanced into the stomach. Endoscopic myotomy will be performed. Mucosal entry will then be closed using endoscopic clips or endoscopic suturing. All patients will recover from their procedures according to standard practice. They will remain nothing per oral (NPO) the night after the procedure and started on intravenous proton pump inhibitors. A gastrografin esophagram will be obtained the next day and if no evidence of leak, the diet will be advanced to a soft diet for two weeks. The patients will be evaluated by study coordinator/PI on a daily basis during their hospitalization. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adult patients age 18 - 80 years old.
- Spastic disorders of the esophagus include spastic (type III) achalasia, distal esophageal spasm (DES), and hypercontractile (jackhammer) esophagus via high resolution esophageal manometry (HRM) 2.
- At least 6 months of symptoms (chest pain, dysphagia, regurgitation and/or weight loss) with no adequate response or intolerance to medical therapy including nitrates and/or calcium channel blockers.
- Overall symptoms score (Eckardt score) > 3
- Ability to understand and the willingness to sign a written informed consent document
Key exclusion criteria (13 listed)
- Diagnosis of spastic esophageal disorder was not confirmed by HRM testing.
- Previous surgery of the esophagus or stomach
- Previous BTX injection at the esophagogastric junction (EGJ) or LES.
- Active severe esophagitis
- Large lower esophageal diverticula
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 |
|---|---|---|
| peroral endoscopic myotomyperoral endoscopic myotomy | Procedure or surgery | peroral endoscopic myotomy |
| Botulinum toxin injectionendoscopic Botulinum toxin (BTX) injection at lower esophagus | Procedure or surgery | Botulinum toxin injection |
Primary outcome
Eckardt score
Time frame: 3-month
symptoms scores
5 secondary outcomes
Eckardt score
Time frame: 1-year
changes in individual symptom scores
Time frame: 3 months and 12 months
changes in esophageal manometry
Time frame: 3 months
rate of complications
Time frame: 3 months and 12 months
quality of life scores
Time frame: 3 months and 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2018.
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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.
Mouen A Khashab, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing peroral endoscopic myotomy and Botulinum toxin injection in people with Esophageal Achalasia and Esophageal Spasm, Diffuse, run by Johns Hopkins 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 8 inclusion and 13 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: withdrawn, as of the sponsor's last update on 12 Jan 2018. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Eckardt score (time frame: 3-month). 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 12 Jan 2018.