ABLATE WEIGHT (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 effects of fundic ablation (FA) 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. The fundic mucosal ablation is not typically done prior to the endoscopic sleeve gastroplasty procedure. When fundic mucosal ablation is sequentially 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 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) on circulating plasma ghrelin, satiation via standard nutrient drink test, and total body weight loss (TBWL), as well as the incidence of adverse events. Fundic ablation will be followed sequentially with ESG, to evaluate the combined impact of FA and ESG (FA-ESG). This study hypothesizes that, compared to baseline, FA-ESG will diminish fasting ghrelin levels, improve satiation, and induce a TBWL ≥ 15% at 12 months.

Official Title
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Gastric Fundus Ablation Plus Endoscopic Sleeve Gastroplasty for Weight Loss

Conditions
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Obesity

Intervention / Treatment
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* Procedure: Fundic Ablation Sequentially 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 TYWL 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: Gastric Fundic Ablation plus Endoscopic Sleeve Gastroplasty<br>Subjects will undergo fundic mucosal ablation followed by endoscopic sleeve gastroplasty | Procedure: Fundic Ablation Sequentially 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 |
| --- | --- | --- |
| Change from Baseline in Fasting Plasma Ghrelin Levels | Change from baseline for the quantitative determination of fasting ghrelin, total plasma measured by EIA/ELISA laboratory assays | Baseline, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, and Month 18 | 
| Change from Baseline in Timed Standardized Nutrient Drink Test | Measure timed consumption of a standardized nutrient drink test utilizing a sensation of satiation visual analogue scale. The severity of symptoms range from 0 (no symptoms) to 5 (maximum or unbearable fullness/satiation) and will measure volume to comfortable fullness (VTF) and maximum tolerated volume (MTV) | Baseline, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, and Month 18 | 
| Change from Baseline in Gastroparesis Cardinal Symptom Index (GCSI) | Assess the severity of patient-reported gastroparesis symptoms. The GCSI gastroparesis symptoms score ranges from 0-none to 5-very severe. High scores reflect greater symptom severity | Baseline, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, and Month 18 | 
| Change from Baseline in Daily Eats: Measuring Daily Eating Factors (DAILY EATS) | Rate the responses to the DAILY EATS questionnaire. The DAILY EATS questionnaire is designed to better understand patient's definitions, experience, and importance, of eating-related factors on a scale of 0-10. The DAILY EATS is a 5-item, patient-reported measure evaluating key eating-related factors (Worst and Average Hunger, Appetite, Cravings, and Satiety) | Baseline, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, and Month 18 | 
| Percent Change in Total Body Weight Loss (TBWL) from Baseline | Measure percent change in total body weight over time following FA alone and FA-ESG. TBWL = pre-op weight - post op body weight. % TBWL is the fraction of body weight expressed in percentage term | Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12, Month 13, Month 14, Month 15, Month 16, Month 17, and Month 18 | 
| Change from Baseline in Weight Efficacy Life-Style Questionnaire Short Form (WEL-SF) composite score | Measure of eating self-efficacy consisting of 8-items on a scale of 0 (not at all confident) to 10 (very confident) | Baseline, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, and Month 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of safety and adverse events | FA and FA-ESG safety will be measured by the rate of serious adverse events (SAEs), adverse events (AEs), and accommodative symptom occurrence | Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12, Month 13, Month 14, Month 15, Month 16, Month 17, and Month 18 |