Clinical trial NCT05711758: Efficacy and Safety of Endoscopic Antral Myotomy as a Novel Weight Loss Procedure
Official title: Efficacy and Safety of Endoscopic Antral Myotomy as a Novel Weight Loss Procedure: A Pilot Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Obesity
Obesity, Morbid
Obesity, Primary
Metabolic Disease
Delayed Gastric Emptying Following Procedure
Keywords: 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
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2023-02-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults in the Center for Weight Management and Wellness program at Brigham and Women's Hospital with a BMI \>35 kg/m2 who are pre-qualified by their insurance as recommended by their specialist to undergo an endoscopic bariatric procedure.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Weight change compared to baseline
timeFrame: Screening, Procedure day, 1 month, 3 month, 6 month, 9 month, 12 months
measure: Adverse Events
timeFrame: Procedure day, 1 month, 3 month, 6 month, 9 month, 12 months
measure: Change in tolerability from procedure day to 12 months
timeFrame: Procedure day, 1 month, 3 month, 6 month, 9 month, 12 months
Secondary outcomes:
measure: Change in Quality of Life compared to baseline
timeFrame: Screening, 1 month, 3 month, 6 month, 9 month, 12 months
measure: Gastric Emptying compared to baseline
timeFrame: Screening, 6 months, 12 months
measure: Ghrelin levels compared to baseline
timeFrame: Screening, 6 months, 12 months
measure: Insulin levels compared to baseline
timeFrame: Screening, 6 months, 12 months
measure: HgA1c levels compared to baseline
timeFrame: Screening, 6 months, 12 months
measure: Glucose levels compared to baseline
timeFrame: Screening, 6 months, 12 months
measure: HOMA-IR blood plasma levels compared to baseline
timeFrame: Screening, 6 months, 12 months
measure: Physiologic Changes of gastric motility/transit compared to baseline
timeFrame: Screening, 6 months, 12 months
measure: Gastric Motility compared to baseline
timeFrame: Screening, 1 month
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Christopher C. Thompson, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Klem ML, Wing RR, Chang CC, Lang W, McGuire MT, Sugerman HJ, Hutchison SL, Makovich AL, Hill JO. A case-control study of successful maintenance of a substantial weight loss: individuals who lost weight through surgery versus those who lost weight through non-surgical means. Int J Obes Relat Metab Disord. 2000 May;24(5):573-9. doi: 10.1038/sj.ijo.0801199.
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citation: Abu Dayyeh BK, Acosta A, Camilleri M, Mundi MS, Rajan E, Topazian MD, Gostout CJ. Endoscopic Sleeve Gastroplasty Alters Gastric Physiology and Induces Loss of Body Weight in Obese Individuals. Clin Gastroenterol Hepatol. 2017 Jan;15(1):37-43.e1. doi: 10.1016/j.cgh.2015.12.030. Epub 2015 Dec 31.
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citation: Aghaie Meybodi M, Qumseya BJ, Shakoor D, Lobner K, Vosoughi K, Ichkhanian Y, Khashab MA. Efficacy and feasibility of G-POEM in management of patients with refractory gastroparesis: a systematic review and meta-analysis. Endosc Int Open. 2019 Mar;7(3):E322-E329. doi: 10.1055/a-0812-1458. Epub 2019 Feb 28.
citation: Mohan BP, Chandan S, Jha LK, Khan SR, Kotagiri R, Kassab LL, Ravikumar NPG, Bhogal N, Chandan OC, Bhat I, Hewlett AT, Jacques J, Ponnada S, Asokkumar R, Adler DG. Clinical efficacy of gastric per-oral endoscopic myotomy (G-POEM) in the treatment of refractory gastroparesis and predictors of outcomes: a systematic review and meta-analysis using surgical pyloroplasty as a comparator group. Surg Endosc. 2020 Aug;34(8):3352-3367. doi: 10.1007/s00464-019-07135-9. Epub 2019 Oct 3.