Gastroesophageal Reflux Disease Research Paper

1.0 Background
Gastroesophageal reflux disease (GERD) is a condition effected to LES (lower esophageal sphincter muscle that can cause various reflux symptom example burning sensation to chest and/or throat and If it is persistent in a long term, it might potential leading to adenocarcinoma of the esophagus.1 In generally, the initial treatment for this condition is medical therapy which provided to relieve acid reflux symptom, However, medical failure can occur in up to 20% of these patient 2,3 In GERD patient with failure Laparoscopic fundoplication is considered to be a standard surgical treatment of GERD4 Nevertheless, management of GERD following Sleeve gastrectomy (SG) in patient with medical refractory GERD is still
challenging due to altering anatomy. Because of previous gastric fundus removing, Laparoscopic fundoplication is unobtainable. Thus, These patient requires the further surgical option which Roux en y Gastric Bypass is a procedure of choice.
In the minimally invasive era, there is various modality target to LES function for GERD therapy have been developed.
The Linx system is a laparoscopic procedure using a magnetic ring placed around the esophagus to augments weaken LES back into normal function. The previous study shows an effectiveness and safety of this device to performed in GERD patient.5 But this is still also having a risk of laparoscopic surgery and might be improperly in alternate anatomy like sleeve gastrectomy patient. Stretta procedure is an endoscopic option which less invasive by using Radio Frequency to the LES to induce fibrosis resulting increased LES pressure and multiple studies also show effectiveness in reducing Proton-pump inhibitor use and also improve the quality of
life.6,7

The Stretta system is endoscopic FDA approved the device for GERD therapy. This device can be an alternative treatment for patients who are not desire or able to undergo surgery. The clinical practice guidelines8 that endorsed Stretta as an appropriate therapy for symptomatic GERD patients with more than 18 year olds who are having at least six months of symptoms and partially or complete response to medical treatment who are unable or unwilling to undergo laparoscopic Nissen fundoplication. Currently, no studies are evaluating Stretta device for management of GERD patients following sleeve gastrectomy. The aims of this prospective cohort study to determine the effectiveness of Stretta device for treatment GERD by following symptomatic questionnaire and quality of life score. 2.0 Rationale and Specific Aims
Study Rationale
The purpose of Investigation:

The GERD study registers patient based on the Clinical Practice Guideline recommendation8. The purpose of the investigation is to identify the subject who meets the following indication and no any contraindication. Indications: Age > 18 years and < 80 years symptomatic GERD patient for at least Six months who are having partial or complete response to medical treatment Contraindications: Patients who condition are not candidates for surgery The study is Prospective cohort study that all the consecutive subjects meet inclusion criteria. The study is designed to collect both safety and effectiveness information.

Study objective

The primary endpoint is a success in term of reducing symptom, as measured by GERD-HRQL (Gastroesophageal Reflux Disease – Health Related The quality of life) questionnaire. This questionnaire is more specific to access the degree of GERD severity than SF-36 questionnaire.9 The treatment is considered successful if improving GERD-HRQL, Reflux symptom index(RSI)

The secondary endpoints in the study are improving in Nutritional status, body weight, BMI, Esophageal acid exposure, LES pressure from manometry, feasibility, safety, and efficacy have also been evaluated. 3.0 Previous Human Studies Recently, there are no studies evaluating Stretta device for management of GERD patients following sleeve gastrectomy. Recently published data evaluate the efficacy of Sterra system in general GERD patients. One multicenter randomize control trial6 Compare Stretta with medication. The result shows no difference in proton pump inhibitor use and quality of life after the end of follow up. And the Stretta procedure also compared with laparoscopic fundoplication.7 The data show similar improve the quality of life and reduce PPI use. 4.0 Inclusion/Exclusion Criteria Inclusion Criteria 1. Symptomatic GERD with age 18 - 80 Years old 2. post Sleeve gastrectomy for one year with symptomatic reflux (heartburn, chest discomfort, asthma/chronic cough, laryngitis, nocturnal aspiration or regurgitation) 3. Diagnosis GERD was documented by 24hr pH monitoring (off medication) 4. On a PPI with GERD-related symptoms would like to discontinue PPI Exclusion criteria
1. Psychiatric disorder
2. Pregnancy
3. Unable or unwilling to sign consent form
4. History of revisions Bariatric surgery
5. Significant mechanical or functional obstruction associated with previous sleeve gastrectomy
6. A hiatal hernia (> 2cm)
7. Grades 3 or 4 esophagitis, Barret's esophagus
8. Gastric or esophageal varices
9. connective tissue disease involved to esophagus and stomach Ex. Scleroderma, SLE
10. Esophageal stricture, Eosinophilic Esophagitis or Achalasia
11. History of small bowel obstruction or inflammatory bowel disease
12. Pacemaker or implanted cardiac defibrillator
13. Coagulopathy or use of anticoagulants
14. Use of immunosuppressive medications 5.0 Enrollment
Sleeve Patients with confirmed diagnosis GERD with taking PPI or other anti-secretory medication will be evaluated. All patients who have a history of GERD met the indication will be asked to participate in this study.
This study is a Prospective cohort study.

6.0 Study Procedures
Study design
The patient who satisfies entry criteria will be asked for complete the questionnaires (GERD-HRQL (table1), Reflux Index Symptom, The Gastrointestinal Quality of Life Index (GIQLI) Questionnaire Index). In the screening phase, Upper GI endoscopy, 24hr pH monitoring and manometry by off anti-secretory medication at baseline will be performed to confirm a diagnosis and also for excluding patient who doesn't meet eligibility criteria. Demographic data and other investigation as individual needs were collected and completed the questionnaires (GERD-HRQL (table1), Reflux Index Symptom, The Gastrointestinal Quality of Life Index (GIQLI) Questionnaire Index) in all satisfying entry criteria patients. The Stretta therapy will be performed an outpatient day hospital basis: deep sedation with continued cardiorespiratory monitoring by an anesthesiologist. All Subjects continue their current PPIs regimen for 30 days following the procedure and then stop PPI medication. If symptom recurrence or not improve, the medication will be started and step up again. Hospital follow up period will be done at six months and 12 months and as needs with complete symptomatic questionnaire and quality of life scores by the patient and other investigation will be done, if indicated (Appendix A)

Detail of Procedure
The Stretta therapy system (Fig.1) involves an upper endoscopy by delivering Radiofrequency energy to several points to Lower esophageal sphincter (LES) via a catheter.
(Fig.2) The device contains with a deflatable balloon with a basket and four electrode needle sheath. The putative mechanism of Stretta focus on increase gastric yield pressure, increase thickness of LES muscle, decrease EG junction compliance without fibrosis, Decrease transient LES relaxations.10
The Stretta procedure will be performed according to the technique described by Triada lopoulos.11 At operating room, the patient was identified by name and operative procedure administrated with general endotracheal tube anesthesia, "the operation will start by diagnostic upper endoscopy to identify gastroesophageal junction, then the endoscope is pulled out, and the RF catheter is introduced over the guide-wire. The balloon of Stretta catheter will inflate at 2 cm proximal to EG junction. Then the electrode needle into the catheter will be deployed and applied radiofrequency energy for 60 seconds. The balloon is deflated, and the catheter will rotate about 45 degrees, then the process is repeated every 0.5 cm, covering an area of 2 cm above and 1.5 cm below EG junction for a total of 22 sets of needle deployments"11.
(Fig.3)

Figure 1: Stretta®, Mederi Therapeutics Inc, Norwalk, CT, USA

Figure 2. the picture shows detail of stretta procedure

Figure 3. Endoscopic appearance of the gastroesophageal junction immediately after Stretta. Antegrade view of the squamocolumnar junction (A); retrograde view of the cardia (B). White coagulation marks are seen circumferentially in both images.

Study Location

The Loyola Center for Metabolic Surgery and Bariatric Care.

7.0 Risk of investigational agent/Devices (side effect)

Potential risks to subjects and precautions taken to minimize risk:

Risks will have reduced by adhering to FDA approved labeling

Potential Risks/Side Effects
The potential risk specific to this procedure are rarely seen, but possible occur these side effect includes transient bleeding, post-operative fever, mucosal injury, chest pain and transient dysphagia, pharyngitis. The other adverse event is a similarity to a patient is undergoing endoscopic with general anesthesia.
General Anesthesia There is always risks with general anesthesia. These may include a reaction to the drugs that the patient receives heart attack or even death. A patient may have a sore throat or hoarseness after the surgery. There may be other unknown risks.

Endoscopy With any endoscopy, there is the risk of making a hole or tear in the esophagus or stomach. A patient may have a sore throat after the endoscopy.

8.0 Reporting of Adverse Events or Unanticipated Problems Involving Risk to Participants or Others During the study period, patients will be evaluated adverse event by an investigator and attending doctor. A patient can make additional clinic visit when feel unanticipated problems occurred. Any adverse events will be reported to The Loyola University Health Sciences Division IRB.

9.0 Study Withdrawal/Discontinuation The patients can discontinue participating in this project any time without affecting to a standard of care. After patient desire to withdraw the project, all study procedure, and follow-up will stop, however, the information already used and disclosed to investigator will continue use. The Principal Investigator, the Institutional Review Board, the regulatory authorities can withdrawal some patient from the project in case of these patients occur serious condition that can't continue as project protocol or in the patient with non-compliance.

10.0 Statistical Considerations

Statistical Analysis All clinical parameters will be record and analysis as mean (standard deviation) for continuous variable data and as a median for non-normal continuous variables and as percentages for categorical variables. Comparison of data will perform using the chi-square test, independent student, t-test, as appropriate. Level of significance will choose at p 12

Protocol Version # / Protocol Date