A Physiologic Analysis of Endoscopic Sleeve Gastroplasty
A Physiologic Analysis of Endoscopic Sleeve Gastroplasty
Nearly 50% of the U.S. adult population have obesity. Efforts to reduce the burden have been
 hindered by the lack of access to effective therapies and poor understanding of obesity
 phenotypes and how patients would respond to each therapy. Endoscopic sleeve gastroplasty
 (ESG) is one of the most commonly performed endoscopic bariatric and metabolic therapies
 (EBMTs) in the U.S. First performed by Thompson and Hawes in 2012, ESG involves the use of a
 Food and Drug Administration (FDA)-cleared endoscopic suturing or plication device to reduce
 the volume of the stomach. At 12 months, patients experience an average of 16.5% total weight
 loss (TWL) with a clinically meaningful reduction in hemoglobin A1c (HbA1c), with the
 durability of up to at least 5 years. In patients who undergo traditional bariatric surgery,
 there are changes in bile acids (BAs), which stimulate secretion of gut hormones resulting in
 alteration of gastric emptying rate. This mechanism is thought to contribute to weight loss
 and early metabolic improvements following bariatric surgery. Furthermore, some studies
 showed a reduction in inflammatory cytokine levels including interleukin-6 (IL-6) and tumor
 necrosis factor (TNF-α) following bariatric surgery, which may explain its effect on
 long-term metabolic improvements. Our group previously demonstrated that following sleeve
 gastrectomy (SG), a surgical analogue of ESG, the satiety and incretin hormones glucagon-like
 peptide-1 (GLP-1) and peptide YY (PYY) increase, while the hunger hormone ghrelin decreases.
 Despite the known efficacy of ESG on weight loss and metabolic comorbidities, its mechanisms
 of action remain poorly understood. To date, there has been only a single study that assessed
 the effect of ESG on hormonal profiles (ghrelin and PYY) and gastric emptying. However, the
 study was limited by 1) lack of data on the major incretin hormone GLP-1, BAs and
 inflammatory markers and 2) differences in techniques.
Nearly 50% of the U.S. adult population have obesity. Efforts to reduce the burden have been
 hindered by the lack of access to effective therapies and poor understanding of obesity
 phenotypes and how patients would respond to each therapy. Endoscopic sleeve gastroplasty
 (ESG) is one of the most commonly performed endoscopic bariatric and metabolic therapies
 (EBMTs) in the U.S. First performed by Christopher C. Thompson and Robert Hawes in 2012, ESG
 involves the use of a Food and Drug Administration (FDA)-cleared endoscopic suturing or
 plication device to reduce the volume of the stomach. At 12 months, patients experience an
 average of 16.5% total weight loss (TWL) with a clinically meaningful reduction in hemoglobin
 A1c (HbA1c), with the durability of up to at least 5 years. In patients who undergo
 traditional bariatric surgery, there are changes in bile acids (BAs), which stimulate
 secretion of gut hormones resulting in alteration of gastric emptying rate. This mechanism is
 thought to contribute to weight loss and early metabolic improvements following bariatric
 surgery. Furthermore, some studies showed a reduction in inflammatory cytokine levels
 including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) following bariatric surgery,
 which may explain its effect on long-term metabolic improvements. Our group previously
 demonstrated that following sleeve gastrectomy (SG), a surgical analogue of ESG, the satiety
 and incretin hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) increase, while
 the hunger hormone ghrelin decreases9. Despite the known efficacy of ESG on weight loss and
 metabolic comorbidities, its mechanisms of action remain poorly understood.

 The goal of this proposal is to examine the effect of ESG on gut hormones, inflammatory
 cytokines, BAs and gastric emptying. In 2017, we reported a new ESG technique, also known as
 distal Primary Obesity Surgery Endoscopy (POSE), where plications are placed in the gastric
 body to reduce its width and length, which appears to be associated with greater weight loss
 compared to the original technique focusing on reducing the fundic size. In addition to
 assisting with the first-in-human ESG cases in 2012 and its iterations using this new
 technique in 2017, the PI, along with her colleagues, has continued to refine the procedure
 details to optimize safety, efficiency, efficacy and generalizability. Currently, the PI is
 leading an observational study assessing the effect of the new ESG technique on various
 metabolic outcomes. An interim analysis of 25 patients showed mean of 20% TWL at 12 months
 with improvement in insulin resistance (IR) and hemoglobin A1c (HbA1c). Our overall
 hypothesis is that there are changes in gut hormones, inflammatory cytokines, BAs and gastric
 emptying following ESG in the direction that lead to weight loss and improvement in IR. To
 date, there has been only a single study that assessed the effect of ESG on hormonal profiles
 (ghrelin and PYY) and gastric emptying. However, the study was limited by 1) lack of data on
 the major incretin hormone GLP-1, BAs and inflammatory markers and 2) differences in
 techniques.
Inclusion Criteria:

 -  Patient is 18-65 years old

 -  Has class I or II obesity (body mass index (BMI) of 30-34.9 and 35-39.9 kg/m2)

 Exclusion Criteria:

 -  Type 2 diabetes mellitus (HbA1c ≥ 6.5%),

 -  use of a weight loss medication within 6 months

 -  history of bariatric surgery or EBMT

 -  Patient is pregnant, breast-feeding, or planning to become pregnant during the course
 of the study.

 -  Patient is unwilling or unable to sign and date the informed consent.

 -  Patient is unwilling or unable to comply with the follow-up study schedule.

 -  Patient for whom endoscopic procedures are contraindicated.