ABLATE WEIGHT 2 (Single-Stage Fundic Ablation Plus ESG for Weight Loss)

Study Overview
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Brief Summary
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The purpose of this research is to investigate the combined effects of fundic ablation (FA) and endoscopic sleeve gastroplasty on circulating plasma ghrelin, satiation, and total body weight loss, as well as the incidence of adverse events. This procedure will be carried out with the HybridAPC (ERBE Elektromedizin GmbH, Tübingen, Germany). The HybridAPC instrument creates an electric current to deliver a safe amount of thermal injury to a portion of the stomach known as the gastric fundus. This thermal injury will target a hormone called ghrelin which is the only known hormone linked to increasing appetite, calorie intake, and weight gain. This procedure is designed to target the bodily effects of appetite control and gastric sensory and motor functions which cause the feeling of fullness and satiation. When fundic mucosal ablation is paired with endoscopic sleeve gastroplasty (ESG), this combined investigational approach may lead to decreased fasting ghrelin levels, improved satiation, and greater total body weight loss than traditional ESG. This study will help determine if the combined impact of FA with ESG within the same endoscopic session should be made available to patients as part of a comprehensive weight loss strategy.

Detailed Description
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Obesity is a chronic disease state driven by the imbalance of caloric intake and expenditure and mediated by multiple central and peripheral pathways that may serve as targets for therapeutic interventions. The endoscopic sleeve gastroplasty (ESG) is a per oral gastric remodeling technique that employs full-thickness suturing to imbricate the stomach along the greater curvature to achieve a restricted, sleeve-like configuration. While the ESG recapitulates the configuration of a gastric sleeve, it has not yet been shown to achieve as robust weight loss outcomes compared to the laparoscopic sleeve gastrectomy (LSG). A major difference between ESG and LSG is that the former does not involve the gastric fundus. The proximal stomach, and the fundus in particular, produces ghrelin, the only known orexigenic hormone, which has been linked to increased calorie intake and weight gain. Studies have observed reduced levels of ghrelin along multiple timepoints following LSG, and this has been attributed to targeting of the fundus, as bariatric surgeries that did not involve the fundus did not see a decrease in circulating plasma ghrelin. In contrast, in a small comparative study of ESG and LSG, patients who had undergone ESG did not show any decrease in fasting ghrelin levels, 8 ostensibly due to fundic-sparing. In this study, the investigators propose to investigate the effects of fundic ablation (FA-ESG) on total body weight loss (TBWL) as well as the incidence of adverse events. Fundic ablation will be followed with ESG, to evaluate the combined impact of FA and ESG (FA-ESG). This study hypothesizes that the combined endoscopic intervention (FA-ESG) will result in significant weight loss while maintaining an acceptable safety profile

Official Title
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Single-Stage Gastric Fundus Ablation and Endoscopic Sleeve Gastroplasty for Weight Loss

Conditions
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Obesity

Intervention / Treatment
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* Procedure: Fundic Ablation in Combination with Endoscopic Sleeve Gastroplasty
* Device: Fundic Mucosal Ablation with ERBE HybridAPC
* Device: Apollo ESG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 21-65 Body mass Index (BMI) ≥30 kilograms per square meter (kg/m²), or ≤50 kg/m² History of at least one unsuccessful dietary effort to lose body weight Willing and able to participate in the study procedures Understand and voluntarily sign the informed consent Approved ESG candidate at True You Weight Loss Access to internet Reliable transportation to and from Cary, North Carolina surrounding area Exclusion Criteria: Younger than 21 years of age Older than 65 years of age Patients on any medications or supplements including those that may influence cholecystokinin (CCK), glucose, growth hormone, insulin and/or somatostatin levels Milk and/or soy allergies History of any stomach manipulation (including repair of hiatal hernia) History of disordered eating Patients who do not give their consent to the enrollment in the study or are incompetent, unconscious or unable to express their consent for any reason Hemoglobin A1c > 7.0 or any patient with symptoms suggestive of gastroparesis or a formal diagnosis of gastroparesis Patients taking the following medications known to impair gastric accommodation: buspirone, mirtazapine Patients taking the following medications known to accelerate or impair gastric emptying: Reglan (metoclopramide), Zelnorm (tegaserod), Motegrity (prucalopride), erythromycin, Motilium (domperidone), opiates, anticholinergic agents Patients who are pregnant or who plan to become pregnant during study duration Use of non-steroidal anti-inflammatory medications without the ability to stop these during study duration Patients on chronic anticoagulation History of functional gastrointestinal disorder, including functional dyspepsia, irritable bowel syndrome, or other syndromes known to affect gastric sensorimotor function. Concurrent use of weight loss medications.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-Stage Gastric Fundic Ablation plus Endoscopic Sleeve Gastroplasty<br>Subjects will undergo fundic mucosal ablation followed by endoscopic sleeve gastroplasty in the same endoscopic session | Procedure: Fundic Ablation in Combination with Endoscopic Sleeve Gastroplasty<br>* Fundic mucosal ablation followed by endoscopic sleeve gastroplasty in the treatment of adults with obesity<br>Device: Fundic Mucosal Ablation with ERBE HybridAPC<br>* Fundic mucosal ablation utilizing approved ERBE HybridAPC<br>Device: Apollo ESG<br>* Using only Apollo ESG as approved per label<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Safety Complications | Occurrence of Grade III - V complications according to the Clavien-Dindo classification | Week 1, Month 1, Month 2, Month 3, Month 4, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12 | 
| Rate of Adverse Events | Occurrence of Adverse Events and Serious Adverse Events | Week 1, Month 1, Month 2, Month 3, Month 4, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Total Body Weight Loss (TBWL) from Baseline | Measure percent change in total body weight over time following FA-ESG. TBWL = pre-op weight - post op body weight. % TBWL is the fraction of body weight expressed in percentage term | Week 1, Month 1, Month 2, Month 3, Month 4, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12 |