Efficacy & Safety of Submucosal Endoscopic Myotomy With Mucosal Flap (SEMF) in the Treatment of Patients With Achalasia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to learn about the safety and usefulness of a procedure called endoscopic submucosal myotomy, which is a new technique in the treatment of achalasia. Achalasia is a disorder involving the lack of smooth muscle relaxation and sustained high pressure in the sphincter (muscle) of the lower esophagus. This may result in symptoms such as difficulty in swallowing, chest pain, regurgitation of food and eventually, weight loss. For more than a decade, a laparoscopic surgical procedure known as Heller myotomy has been the primary treatment for achalasia in patients with low surgical risk. In Heller myotomy, the surgeon makes three to four small abdominal incisions, inserts tube-like instruments through them, and once inside, the junction between the esophagus and stomach is found, a lengthwise incision is made on the muscular ring surrounding the lower esophageal sphincter which weakens the muscle and the lower esophageal sphincter or muscle (LES) is then able to open more easily. However, there is an emerging field known as natural orifice (opening) transluminal (through the lumen) endoscopic surgery (NOTES). This approach involves passing an endoscope - a thin tube with a built-in camera, light and minuscule tools through the natural opening in the body, like the mouth in order to perform less invasive surgery without any external wounds or scars. The procedure is done using the Submucosal Endoscopy with Mucosal Flap (SEMF) technique which involves passing an endoscope through the mouth into the esophagus, where a small incision is made on the lining of the esophagus, known as the mucosa. A balloon is then inserted and dilated in the submucosa - the layer between the inner lining of the esophagus and the outer wall consisting of the muscle of the esophagus. Dilation of the balloon in the submucosa creates a tunnel that allows insertion of the endoscope and access to the muscle of the lower esophageal sphincter (LES). A long incision is then carefully made on the posterior portion of the muscular ring that forms the LES. The incision divides the muscle fibers of the LES, which weakens the muscle, allowing for the easier passage of food while preserving some valve function to prevent reflux of acid from the stomach into the esophagus. The expected duration of participation is up to 10 years from the time study participants undergo the endoscopic surgical procedure.

Detailed Description
-----------------
The safety of the procedure and feasibility of the study will be measured by improvement in subjects' symptoms score, decrease in LES pressure, as well as the number and severity of complications or adverse events experienced by the subjects. A modified Eckhardt dysphagia assessment tool will be used in grading the dysphagia symptoms.

Official Title
-----------------
A Prospective, Single Center, Proof of Concept Pilot Study of the Efficacy and Safety of Submucosal Endoscopic Myotomy With Mucosal Flap (SEMF) Technique in the Treatment of Patients With Achalasia

Conditions
-----------------
Achalasia, Dysphagia

Intervention / Treatment
-----------------
* Procedure: Submucosal endoscopic myotomy with mucosal flap technique
* Procedure: Submucosal Endoscopic Mucosal Flap (SEMF) technique


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients 18 years or older, male or female, belonging to any race or ethnic origin Patients with manometric positive diagnosis of achalasia, with corresponding symptoms of dysphagia, regurgitation of food or chest pain Patients who are willing and competent to sign Informed Consent and to comply with study related visits and procedures Exclusion Criteria: Patients who are below 18 years of age Presence of coagulopathy Pregnancy Patients who, in the investigator's opinion, are medically unstable, are unable to give informed consent, or whose risks outweigh the benefits of participating in the study Vulnerable subjects: Prisoners, persons with decisional incapacity, and any person who are directly involved in the study, including their immediate family members, and anybody who may have any conflict of interest such as employees of ERBE, USA.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Submucosal Endoscopic Mucosal Flap Technique<br>Submucosal Endoscopic Mucosal Flap Technique | Procedure: Submucosal endoscopic myotomy with mucosal flap technique<br>* Submucosal Endoscopy with Mucosal Flap (SEMF) technique involves the following: (1) injecting 0.9 % normal saline solution to create a submucosal cushion, (2) tiny cut is made into the cushion, (3) Balloon will be used to dilate the opening and allow passage of endoscope in the submucosal space, (4) Upon direct visualization of the muscle fibers, the doctor will cut the circular layers of the diseased muscles, and (5) Tiny clips will be used to close the tiny cut made earlier.<br>* Other names: Natural Orifice Transluminal Endoscopic Surgery (NOTES);Procedure: Submucosal Endoscopic Mucosal Flap (SEMF) technique<br> <br> * Other names: Natural Orifice Transluminal Endoscopic Surgery;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lower esophageal sphincter pressure (LES) | High Resolution Esophageal Manometry will be done at 3 months to measure LES and the result will be compared to baseline or pre-endoscopic myotomy LES pressure. | at 3 months post endoscopic myotomy | 
| Change in frequency of dysphagia | Swallowing difficulty (dysphagia) will be assessed using the Modified Eckhardt Dysphagia Assessment Tool which includes asking the patient how often he/she experiences swallowing difficulty (0 = none, 1 = occasional, 2 = daily, and 3 = every meal. The score will be compared to pre-myotomy score. | 4 weeks post procedure | 
| Change in frequency of Regurgitation | Patient will be asked how often he/she brings up swallowed liquid/solid food or regurgitates (0 = none, 1 = occasional, 2 = daily, and 3 = every meal. The score will be compared to the score prior to the procedure. | 4 weeks post procedure | 
| Change in frequency of chest pain | The patient will be asked how often he/she experiences chest pain and the frequency (0 = none, 1 = occasional, 2 = daily, and 3 = every meal. The score will be compared to pre-myotomy score. | 4 weeks post procedure | 
| Presence of perforation | Presence of perforation that is seen during the endoscopic procedure. | During endoscopic myotomy procedure | 
| Presence of bleeding | Occurence of bleeding during the procedure. | During endoscopic myotomy procedure | 
| Presence of mediastinal emphysema | Presence of mediastinal emphysema will be recorded. | During endoscopic myotomy procedure | 
| Presence of Infection | Presence of infection within the first 4 weeks post myotomy will be recorded. | 4 weeks post procedure | 
| Development of stricture at the myotomy site. | Development of stricture will be assessed by performing an upper endoscopy for patients with change in their Modified Dysphagia Score. | 3 months post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence and frequency of heartburn | The patient will be asked for presence or absence of heartburn. If present, he/she will be asked for frequency (0 = none, 1 = occasional, 2 = daily, and 3 = every meal). The score will be compared to pre-myotomy score. | 4 weeks post procedure | 
| Frequency of use of antacids (PPI, H-2 antagonists) | The patient will be asked if he/she is using any type of antacid. If using antacid, he/she will be asked how often he/she is using it (0 = none, 1 = occasional, 2 = daily, and 3 = every meal). The score will be compared to pre-myotomy score. | 4 weeks post procedure | 
| Change in patient's weight | Post myotomy weight will be measured and recorded and compared to pre-myotomy weight. | At 3, 6, 9, and 12 months post procedure. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Submucosal endoscopic myotomy, Per Oral Endoscopic Myotomy, Natural Orifice Transluminal Endoscopic Surgery