Clinical trial NCT02663206: Peroral Endoscopic Myotomy Versus Botulinum Toxin Injection in Spastic Esophageal Disorders
Official title: Peroral Endoscopic Myotomy Versus Botulinum Toxin Injection in the Treatment of Medical Refractory Spastic Esophageal Disorders
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Esophageal Achalasia
Esophageal Spasm, Diffuse
Esophageal Motility Disorders
Keywords: spastic esophageal disorders
achalasia
diffuse esophageal spasm
hypercontractile (jackhammer) esophagus
Botulinum toxin injection
peroral endoscopic myotomy
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2016-01-26
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Eckardt score
timeFrame: 3-month
Secondary outcomes:
measure: Eckardt score
timeFrame: 1-year
measure: changes in individual symptom scores
timeFrame: 3 months and 12 months
measure: changes in esophageal manometry
timeFrame: 3 months
measure: rate of complications
timeFrame: 3 months and 12 months
measure: quality of life scores
timeFrame: 3 months and 12 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Mouen A Khashab, MD
role: PRINCIPAL_INVESTIGATOR
References: