Peroral Endoscopic Myotomy Versus Botulinum Toxin Injection in Spastic Esophageal Disorders

NCT ID: NCT02663206

Last Updated: 2018-01-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2020-07-31

Brief Summary

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.

Conditions

Esophageal Achalasia; Esophageal Spasm, Diffuse; Esophageal Motility Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Botulinum toxin injection

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)

Group Type: OTHER

Botulinum toxin injection

Intervention Type: PROCEDURE

endoscopic Botulinum toxin (BTX) injection at lower esophagus

peroral endoscopic myotomy

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.

Group Type: OTHER

peroral endoscopic myotomy

Intervention Type: PROCEDURE

peroral endoscopic myotomy

Interventions

peroral endoscopic myotomy

peroral endoscopic myotomy

Intervention Type: PROCEDURE

Botulinum toxin injection

endoscopic Botulinum toxin (BTX) injection at lower esophagus

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Adult patients age 18 - 80 years old.

2. 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.

3. 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.

4. Overall symptoms score (Eckardt score) > 3

5. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

1. Diagnosis of spastic esophageal disorder was not confirmed by HRM testing.

2. Previous surgery of the esophagus or stomach

3. Previous BTX injection at the esophagogastric junction (EGJ) or LES.

4. Active severe esophagitis

5. Large lower esophageal diverticula

6. Large > 3cm hiatal hernia

7. Megaesophagus (> 6 cm)

8. Sigmoid esophagus

9. Known gastroesophageal malignancy

10. Inability to tolerate sedated upper endoscopy due to cardiopulmonary instability, severe pulmonary disease or other contraindication to endoscopy

11. Cirrhosis with portal hypertension, varices, and/or ascites

12. 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.

13. Pregnant or breastfeeding women (all women of child-bearing age will undergo urine pregnancy testing)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mouen A Khashab, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

IRB00049663

Identifier Type: -

Identifier Source: org_study_id