Clinical Trial for Weight Regain Post-RYGB: APC Versus APC Plus Endoscopic Suture Technique

Study Overview
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Brief Summary
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Obesity is a worldwide health and sociopolitical problem. Excessive body-weight currently affects over 50% of the Brazilian population. It has been well established that obesity is an independent health risk. Obese individuals are at increased to extremely high risk for many diseases and for early death relative to those with normal weights and waist circumferences. The increased disease susceptibility for this subset of patients includes hypertension, stroke, hyperlipidemia, sleep apnea, Type 2 diabetes, neoplasms, Gastro-Esophageal Reflux Disease, and musculoskeletal disorders. Bariatric surgery is the most effective treatment for obesity. As bariatrics grow, the number of patients suffering from surgical-related complications also grows. One of the most worrisome long-term complications is weight regain, once the patient may be again affected by overweight-related comorbidities and face again pre-operative esthetic issues. This trial focus on testing efficacy and safety of two endoscopic revisional procedures in patients suffering from weight regain following Roux-en-Y Gastric Bypass: Ablation with Argon Plasma Coagulation (APC) versus APC plus Endoscopic Full-thickness Suture (with Apollo Overstitch device). Pouch volume, gastric emptying and gut hormones changes will also be assessed.

Detailed Description
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Obesity is a worldwide health and sociopolitical issue. Excessive body-weight currently affects over 50% of the Brazilian population and around 13% of all world population. It has been well established that obesity is an independent risk factor. Obese individuals are at increased risk of diseases and earlier death compared to those with normal weight and waist circumferences. The increased disease susceptibility of this subset of patients includes hypertension, stroke, hyperlipidemia, sleep apnea, Type 2 diabetes, neoplasms, GERD, and musculoskeletal disorders. Obese patients and their physicians have increasingly turned to surgery to solve the excess weight issue and the frequent co-morbid conditions that impact their health and quality of life. Roux-en-Y Gastric Bypass (RYGB) and Laparoscopic Gastric Banding (LGB) comprise around 70% of all weight loss procedures performed every year. They induce significant and perennial weight loss and reduce or eliminate associated co-morbid diseases, including Type 2 diabetes. Despite improvements in postoperative morbidity and mortality rates over the years, (in part due to the use of a laparoscopic approach), these procedures still carry significant risk. Recent studies have shown mortality rates with RYGB as high as 1.9%, and complications associated with LGB as high as 13%. Nonetheless, a secondary bariatric procedure due to weight regain carries significant complication rates and worse outcomes, compared to the primary procedure. Consequently, less invasive techniques are needed to reduce such risks. Gastric restriction is an important principle of both RYGB and LGB. The OverStitchTM Endoscopic Suturing System (Apollo Endosurgery, Inc. Austin, Texas) is an approved device designed to endoscopic placement of suture(s) and approximation of soft tissue. This system offers the assistant doctor the ability to restrict gastric pouch size by approximating tissue endoluminally through an incisionless (per-oral) approach. The use of this system has the potential to reduce the complications associated with the current surgical approach but still reaching the desired gastric restriction. The OverStitch has safely been used clinically for a great number of procedures that demanded an incisionless or minimally invasive approach, including endoluminal revisions for post-bypass gastric stoma and/or pouch dilatation, post-bypass fistulae repair, and oversewing of marginal ulcers. Besides this suturing device, other endoscopic methods have already been used to reduce dilated stoma. Among them, ablation with argon plasma coagulation (APC) is one of the most important since this device is worldly available and presents an acceptable cost. Recent studies associate APC prior to endoscopic suture and initial evidence supports superiority of this association. However, literature is still lacking of studies to support the use of APC associated with endoscopic suturing instead of APC alone. Therefore, the main focus of this study is to directly compare short and long-term effectiveness and safety of APC versus APC plus Endoscopic Full-thickness suture with OverStitch device in patients suffering from weight regain following RYGB. Moreover, gut hormones regulation regarding bariatric and revisional procedures have been studied recently and evidence suggests that hormonal changes may be an important factor in weight loss. Three of the most important gut hormones regarding weight balance are ghrelin, GLP1 and peptide YY. Ghrelin is known as hunger hormone. It is produced by cells in gastric fundus. Glucagon-like Peptide 1 (GLP1) and Peptide YY (PYY) are both hormones that regulate satiety and are produced by L cells along distal intestine. Evidence in bariatric show that after long-term ghrelin levels diminish while GLP and PYY reach higher post-prandial peak. Regarding revisional endoscopic therapy, gut hormone changes have never been studied. That is also focus of this study as secondary outcome.

Official Title
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Randomized Clinical Trial for Weight Regain Post-RYGB:Argon Plasma Coagulation Versus Argon Plasma Coagulation Plus Endoscopic Suture Technique

Conditions
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Obesity

Intervention / Treatment
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* Procedure: APC
* Device: Endoscopic Suture Technique (OverStitch TM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has stoma dilation defined as greater than 12mm, assessed with an esophagogastroduodenoscopy performed pre-operatively Subject is ≥ 18 yrs. of age and ≤ 60 yrs. of age Subject has a BMI of > 30 Subject has history of obesity for > 2 yrs Subject has had no significant weight change (<5% of total body weight) in last 6 months Subject must have failed standard obesity therapy (diet, exercise, behavior modification, and pharmacologic agents either alone or in combination), which will be assessed through an interview performed by a team member of the study at baseline Subject is a reasonable candidate for general anesthesia Subject agrees not to have any additional weight loss surgery or reconstructive surgery that may affect body weight (i.e. mammoplasty, liposuction, lipoplasty, etc) during the trial Subject must be willing and able to participate in all aspects of the study and agree to comply with all study requirements for the duration of the study. This includes availability of reliable transportation and sufficient time to attend all follow-up visits. Subject must be able to fully understand and be willing to sign the informed consent. Exclusion Criteria: Subject has had significant weight loss in the last 3 months, or between baseline and the study procedure Mallampati (intubation) score greater than 3 Subject is observed during esophagogastroduodenoscopy to have heavily scarred, malignant or poor quality/friable tissue in areas of the stomach where sutures are to be placed Subject has history of inflammatory disease of GI tract Subject has a history of intestinal strictures or adhesions Subject has renal and/or hepatic insufficiency Subject has chronic pancreatic disease Subject has history of/or signs and/or symptoms of gastro-duodenal ulcer disease and/or active peptic ulcer Subject has significant esophageal disease including Zenker's diverticulum, grade 3-4 reflux esophagitis, stricture, Barrett's esophagus, esophageal cancer, esophageal diverticulum, dysphagia, achalasia, or symptoms of dysmotility Subject has a history of any significant abdominal surgery Subject has had previous bariatric, gastric or esophageal surgery; intestinal obstruction; portal gastropathy; gastrointestinal tumors; esophageal or gastric varices, or gastroparesis Subject has a hiatal hernia > 2cm Subject has chronic/acute upper GI bleeding conditions Subject has severe coagulopathy (prothrombin time > 3 seconds over control or platelet count < 100,000) or is presently taking heparin, coumadin, warfarin, or other anticoagulants or other medications which impede coagulation or platelet aggregation, if they cannot be ceased for the procedure Female subject is of childbearing age and not practicing effective birth control, is pregnant or is lactating Subject has symptomatic congestive heart failure, cardiac arrhythmia or unstable coronary artery disease. Subject has cancer or life expectancy of < 2 yrs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group A<br>This group own twenty patients who met all the inclusion criteria. These will be treated with APC. | Procedure: APC<br>* Ablation of the dilated gastro-jejunal anastomosis with Argon Plasma Coagulation. This procedure induces cicatrization process around the stoma and propitiates its reduction.<br>|
| Active Comparator: Group B<br>This group own twenty patients who met all the inclusion criteria. These will be treated with APC plus Endoscopic Suture Technique (OverStitch TM). | Procedure: APC<br>* Ablation of the dilated gastro-jejunal anastomosis with Argon Plasma Coagulation. This procedure induces cicatrization process around the stoma and propitiates its reduction.<br>Device: Endoscopic Suture Technique (OverStitch TM)<br>* OverStitchTM Endoscopic Suturing System. Stitches will be placed per-orally with the aforementioned device around the dilated stoma in order to reduce the diameter of the anastomosis. In this group, ablation with APC will be done immediately before suturing.<br>* Other names: Apollo Overstitch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Weight Loss | Absolute Weight Loss will be assessed through subtraction of the pre-operative weight and the weight at follow-up, and will be measured in kilograms (kgs). | This outcome will be assessed at 12 months after the procedure | 
| Excess Weight Loss | Excess Weight Loss will be assessed through calculation of the percentage of the overweight lost after the procedure at follow-up. Excess Weight is defined as the weight over BMI of 25 for each patient. Excess Weight Loss will be expressed as percentage (%). | This outcome will be assessed at 12 months after the procedure | 
| Abdominal Circumference Reduction | Subtraction between baseline abdominal circumference and this measure at follow-up. This outcome will expressed in centimeters (cm). | This outcome will be assessed at 12 months after the procedure | 
| BMI reduction | Subtraction between baseline BMI and this measure at follow-up. This outcome will expressed in kg/m2. | This outcome will be assessed at 12 months after the procedure. | 
| Diabetes improvement | This outcome will be assessed through a glucose tolerance test performed at baseline and another one performed at 1 year follow-up. | This outcome will be assessed at baseline and 12 months after the procedure. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Adverse Events | Adverse events such as perforation, bleeding, pain, stenosis, vomiting, need of surgery. | This outcome will be assessed continually after the procedure. | 
| Quality of Life Improvement | This outcome will be assessed with SF-36 questionnaire. | This outcome will be assessed at baseline and at 12 months. | 
| Eating Habits Evaluation | This outcome will evaluate if there is any change in eating habits with TFEQ-R21 questionnaire | This outcome will be assessed at baseline and at 12 months. | 
| Gut Hormones Response | This outcome will evaluate at fasting, 30, 60, 90 and 120 minutes post-prandial the hormonal variation regarding Ghrelin, GLP1 and PYY | This outcome will be assessed at baseline and at 12 months. | 
| Gastric (Pouch) Emptying | This outcome will evaluate retention rate through scintigraphy. | This outcome will be assessed at baseline and at 12 months. | 
| CT Volumetry of the Gastric Pouch | This outcome will evaluate volumetry of the pouch before and 12 months after procedure through tridimensional computed tomography. | This outcome will be assessed at baseline and at 12 months. |