Efficacy and Safety of Endoscopic Antral Myotomy as a Novel Weight Loss Procedure

Study Overview
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Brief Summary
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Gastric myotomy has been performed for several years as a means of addressing chronic stenosis after sleeve gastrectomy and treating gastroparesis. The Pylorus Sparing Antral Myotomy (PSAM) technique has the opposite effect by leaving the pylorus intact and extending the myotomy proximally to the distal gastric body. PSAM was initially combined with ESG and shown to delay gastric emptying and provide greater weight loss without impacting tolerability (GCSI score) or the safety profile of the procedure (2 DDW GEM abstracts). PSAM has not been evaluated alone, without concomitant ESG. Since delayed gastric emptying alone is known to promote weight loss, it is thought that PSAM alone (without ESG) may provide similar efficacy, while reducing procedure time and adverse events. There have been no clinical studies that investigate the efficacy of PSAM independent of ESG. This pilot study aims to address this lack of information by evaluating the safety, tolerability, and short-term efficacy of PSAM, in addition to exploring its impact on gastric physiology. This will also provide data that may be used in designing a larger clinical trial.

Detailed Description
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Obesity, defined as body mass index (BMI) greater than 30 kg/m2 in adults, is affecting 30% of the global population and a significant healthcare burden. [1] Obesity has increased dramatically over the last few decades, with over 650 million adults, or 13% of the world's total adult population, diagnosed with the disease in 2016 - a figure that has nearly tripled since 1975.[1] In the U.S the obesity prevalence for U.S. adults increased from 14.1% to 26.7%, or an 89.9% increase between 1993 and 2008.[1,2,3] As a result, current and potential interventions, and treatment strategies to combat obesity have become more important. The current treatment of obesity involves multiple strategies with combination of non-pharmacologic, pharmacologic, endoscopic, and surgical interventions. There are several FDA-approved pharmacotherapies for the treatment of obesity such as orlistat, phentermine-topiramate, naltrexone-bupropion, liraglutide, and semaglutide. For adults with a body mass index (BMI) of 40 kg/m2 or 35 kg/m2 and obesity-related comorbidity, bariatric surgery can be offered. [4, 5] Endoscopic bariatric and metabolic therapies (EBMT) have emerged as an alternative treatment for patients with obesity with a BMI over 30kg/m2 or 27 kg/m2 with an obesity-related comorbidity. The interest in EBMT is growing given their safety, efficacy, and non-invasive nature. Current FDA-cleared devices that can be used for EBMT include intragastric balloons and suturing devices for endoscopic sleeve gastroplasty (ESG). Additionally, a variety of Endo surgical knifes are approved for tissue dissection such as myotomy. Gastric interventions used to treat obesity work by interfering with gastric accommodation, breakdown and mixing of food, or gastric emptying. Delaying gastric emptying was shown to be a major mechanism of action for both ESG and IGB which is also correlated with weight loss [6]. Antral peristalsis constitutes an important mechanism for gastric emptying. The antrum also serves as a food sensor which needs to be filled to a certain level before food is pumped into the duodenum. [7] Therefore, targeting the antrum is a feasible strategy to delay gastric emptying, induce satiety, and promote weight loss. In fact, one of the recently FDA-cleared EBMT devices, the Transpyloric Shuttle (Baronova, MA), focuses on inhibiting the antral pump as its primary mechanism of action. This device consists of two interconnected large and small bulbs, positioned in the antrum and duodenum respectively, that cause intermittent obstruction of the pylorus, leading to a delay in gastric emptying (10). As such, a pylorus sparing antral myotomy (PSAM) with a submucosal tunneling technique was developed. Gastric myotomy has been performed for several years as a means of addressing chronic stenosis after sleeve gastrectomy and treating gastroparesis. The PSAM technique has the opposite effect by leaving the pylorus intact and extending the myotomy proximally to the distal gastric body. PSAM was initially combined with ESG and shown to delay gastric emptying and provide greater weight loss without impacting tolerability (GCSI score) or the safety profile of the procedure (2 DDW GEM abstracts). PSAM has not been evaluated alone, without concomitant ESG. Since delayed gastric emptying alone is known to promote weight loss, it is thought that PSAM alone (without ESG) may provide similar efficacy, while reducing procedure time and adverse events. Traditional bariatric surgery is very effective at treating obesity, however, only 1% of eligible patients elect to undergo this treatment option. Additionally, the majority of patients with obesity do not qualify for bariatric surgery. [5] Due to the less invasive nature of PSAM, and relative technical simplicity compared to ESG) this procedure may provide a more widely available and more acceptable treatment option for some patients. There have been no clinical studies that investigate the efficacy of PSAM independent of ESG. This pilot study aims to address this lack of information by evaluating the safety, tolerability, and short-term efficacy of PSAM, in addition to exploring its impact on gastric physiology. This will also provide data that may be used in designing a larger clinical trial.

Official Title
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Efficacy and Safety of Endoscopic Antral Myotomy as a Novel Weight Loss Procedure: A Pilot Study

Conditions
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Obesity, Obesity, Morbid, Obesity, Primary, Metabolic Disease, Delayed Gastric Emptying Following Procedure

Intervention / Treatment
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* Procedure: PSAM Treatment Patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects must be 18-70 years of age eligible for endoscopic and surgical weight loss procedures body mass index (BMI) greater than 35 kg/m2 Individuals must be in excellent mental health able to understand and sign informed consent available to return for all routine follow-up study visits Exclusion Criteria: untreated H. pylori infection gastroparesis active smoking an ongoing or a history of treatment with opioids in the last 12 months prior to enrollment previous pyloromyotomy or pyloroplasty gastrointestinal obstruction severe coagulopathy esophageal or gastric varices and/or portal hypertensive gastropathy pregnancy or puerperium any inflammatory disease of the gastrointestinal tract (including but not limited to severe (LA Grade C or D) esophagitis, active gastric ulceration, active duodenal ulceration, or specific inflammation such as Crohn's disease) malignant or premalignant gastric diseases (such as high grade dysplasia, gastric cancer, or GIST) severe cardiopulmonary disease or a history of coronary artery disease (including myocardial infarction within the past 6 months, poorly controlled hypertension, required use of NSAIDs) lactation history of gastrointestinal surgery any serious health condition unrelated to their weight that would increase the risk of endoscopy chronic abdominal pain active psychological issues preventing participation in a lifestyle modification program a known history of endocrine disorders affecting weight (uncontrolled hypothyroidism) an inability to provide informed consent use of any medication that may interfere with weight loss use of any medication that may interfere with gastric emptying any other condition which the investigator may deem as an impediment to compliance or hinder completion of the proposed study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PSAM Treatment Patients<br>Subjects having esophagogastroduodenoscopy (EGD) with Pylorus Sparing Antral Myotomy (PSAM) with standard of care lifestyle modification therapy. | Procedure: PSAM Treatment Patients<br>* PSAM is a pylorus-sparing antral myotomy performed under general anesthesia. Endoscopic myotomy is then performed applying the principles of submucosal endoscopy and techniques used during gastric per-oral endoscopic myotomy (G-POEM). A submucosal bleb is created proximal to the pylorus. A longitudinal mucosal incision is made with an endoscopic knife. The endoscope is then introduced into the submucosal space, and the knife is used to dissect the submucosal fibers. Antral myotomy is performed starting proximal to the pyloric ring extending to the mucosal access site. The myotomy entails cutting of the inner circular and oblique muscle bundles or may be full thickness at the discretion of the endoscopist. The mucosal entry is then closed using endoscopic suturing or clips.<br>* Other names: PSAM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight change compared to baseline | Percent total body weight loss | Screening, Procedure day, 1 month, 3 month, 6 month, 9 month, 12 months | 
| Adverse Events | Changes to health compared to baseline | Procedure day, 1 month, 3 month, 6 month, 9 month, 12 months | 
| Change in tolerability from procedure day to 12 months | How the subjects feel after the procedure based on pain scale and AE's | Procedure day, 1 month, 3 month, 6 month, 9 month, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life compared to baseline | Overall quality of life questionnaire | Screening, 1 month, 3 month, 6 month, 9 month, 12 months | 
| Gastric Emptying compared to baseline | Gastric emptying using a gastric emptying breath test (GEBT) | Screening, 6 months, 12 months | 
| Ghrelin levels compared to baseline | Laboratory analysis of blood samples to test ghrelin levels | Screening, 6 months, 12 months | 
| Insulin levels compared to baseline | Laboratory analysis of blood samples to test insulin metabolic profiles | Screening, 6 months, 12 months | 
| HgA1c levels compared to baseline | Laboratory analysis of blood samples to test HgA1c metabolic profiles | Screening, 6 months, 12 months | 
| Glucose levels compared to baseline | Laboratory analysis of blood samples to test Glucose metabolic profiles | Screening, 6 months, 12 months | 
| HOMA-IR blood plasma levels compared to baseline | Laboratory analysis of blood samples to test changes in insulin resistance | Screening, 6 months, 12 months | 
| Physiologic Changes of gastric motility/transit compared to baseline | Upper GI series comparing pre-procedure barium transit to post-procedure 6 and 12 month time points. | Screening, 6 months, 12 months | 
| Gastric Motility compared to baseline | Dynamic MRI | Screening, 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pylorus Sparing Antral Myotomy (PSAM), Gastric physiology, Gastric emptying, Pylorus-sparing antral myotomy, Myotomy, Endoscopic Sleeve Gastroplasty (ESG), TransPyloric Shuttle (TPS), Intragastric balloon (IGB), Endoscopic bariatric and metabolic therapies (EBMT), Gut Hormones, Gastric Emptying Breath Test