Hormonal and Microbiota Modulation After Endoscopic Sleeve Gastroplasty

Official title

Roles of Hormonal Modulation and the Microbiota in Gastric Emptying and Metabolic Response After Endoscopic Sleeve Gastroplasty

Overview

Obesity is a chronic disease with a rapidly increasing prevalence, expected to affect up to 25% of the French population by 2030, and is associated with significant morbidity, mortality, and healthcare burden. Bariatric surgery, including sleeve gastrectomy and gastric bypass, remains the standard treatment for severe obesity but is irreversible and carries procedural risks. Less invasive alternatives have emerged, including pharmacological treatments (GLP-1 receptor agonists and multi-agonists) and endoscopic approaches such as endoscopic sleeve gastroplasty (ESG), which have shown efficacy in weight loss and metabolic improvement, although drug therapies are limited by weight regain after discontinuation. Sleeve gastrectomy, the most frequently performed bariatric procedure in France, induces weight loss through gastric restriction and hormonal changes, including decreased ghrelin and increased GLP-1 and PYY, along with accelerated gastric emptying. ESG is a minimally invasive endoscopic technique with mechanisms that remain incompletely understood, likely involving gastric restriction, altered gastric emptying, and hormonal and microbiome-related effects. Bariatric outcomes are driven by complex interactions between gastric anatomy, motility, hormonal regulation, and the gut microbiome. An integrated evaluation of these parameters is needed to better understand response variability after intervention. A total of 40 patients will be enrolled (20 per group).

Detailed description

Obesity is a chronic disease with increasing prevalence, projected to affect up to 25% of the French population by 2030, and is associated with significant morbidity, mortality, and healthcare burden. Bariatric surgery, including sleeve gastrectomy and gastric bypass, remains the reference treatment for severe obesity but is irreversible and associated with procedural risks.

Less invasive alternatives have emerged, including pharmacological treatments (GLP-1 receptor agonists and multi-agonists) and endoscopic procedures such as endoscopic sleeve gastroplasty (ESG). These approaches have demonstrated efficacy in weight loss and metabolic improvement, although pharmacological treatments are limited by weight regain after discontinuation and reduced long-term adherence.

Sleeve gastrectomy, the most commonly performed bariatric procedure in France, induces weight loss through gastric restriction, hormonal changes (including reduced ghrelin and increased GLP-1 and PYY), and accelerated gastric emptying. In contrast, ESG is a minimally invasive endoscopic technique with mechanisms that remain incompletely understood, with emerging data suggesting delayed gastric emptying.

Beyond mechanical restriction, the metabolic effects of bariatric interventions involve complex interactions between gastric anatomy, motility, gut hormones, and the microbiome. Gastric emptying, a key determinant of satiety and hormonal response, differs between procedures and may contribute to variability in weight loss outcomes. Hormonal adaptations and microbiome changes after ESG remain insufficiently characterized.

This study adopts an integrative approach combining gastric volumetry, gastric emptying assessment, hormonal profiling, and microbiome analysis to better understand mechanisms of response and inter-individual variability after bariatric interventions.

A total of 40 patients will be enrolled (20 per group), with treatment allocation determined by a multidisciplinary team. Participants will undergo serial assessments including blood sampling, standardized meal test hormone measurements, CT-based gastric volumetry, and gastric emptying scintigraphy. Endoscopic biopsies will be performed at 12 months in the ESG group, while gastroscopy in the surgical group will be performed only if clinically indicated.

The study aims to improve mechanistic understanding of bariatric interventions, identify predictors of response, and support personalized therapeutic strategies in obesity management.

Interventions

• Procedure Laparoscopic sleeve gastrectomy
  Participants undergo laparoscopic sleeve gastrectomy with 12-month follow-up including clinical, metabolic, imaging, hormonal and microbiota assessments.
• Procedure Endoscopic sleeve gastroplasty
  Participants undergo endoscopic sleeve gastrectomy with 12-month follow-up including clinical, metabolic, imaging, hormonal and microbiota assessments.

Primary outcome measures

• Gastric emptying evolution after endoscopic sleeve gastroplasty versus surgical sleeve [Time frame: Baseline to 12 months post-intervention]

Secondary outcome measures (12)

• Gastric microbiota diversity assessed by 16S rRNA sequencing [Time frame: Baseline to 12 months]
• Total Body Weight Loss (TBWL) [Time frame: Baseline, 1, 3, 6 and 12 months]
• Postprandial GLP-1 plasma concentration after standardized meal test [Time frame: Baseline, 1, 3, 6 and 12 months]
• Correlation between gastric emptying and GLP-1 plasma levels [Time frame: Baseline to 12 months]
• Correlation between gastric emptying and PYY plasma levels [Time frame: Baseline to 12 months]
• Correlation between gastric emptying and GIP plasma levels [Time frame: Baseline to 12 months]
• Correlation between gastric emptying and ghrelin plasma levels [Time frame: Baseline to 12 months]
• Gastric volume assessed by CT-based volumetry [Time frame: Baseline, 1 month and 12 months]
• Effect of gastric emptying time on total body weight loss [Time frame: Baseline to 12 months]
• Effect of postprandial GLP-1 plasma concentration on total body weight loss [Time frame: Baseline to 12 months]
• Effect of gastric volume on total body weight loss [Time frame: Baseline to 12 months]
• Effect of gastric microbiota diversity on total body weight loss [Time frame: Baseline to 12 months]

Eligibility criteria

Inclusion criteria

• Male or female, age ≥ 18 years
• BMI between 30 and 40 kg/m²
• With or without obesity-related comorbidities (hypertension, diabetes, -obstructive sleep apnea, etc.)
• Indication for ESG (Endoscopic Sleeve Gastroplasty) or surgical sleeve gastrectomy validated in a multidisciplinary team meeting
• Patient with an indication to undergo CT scan and scintigraphy
• Written informed consent
• Affiliation with a health insurance system

Exclusion criteria

• Patient receiving anti-obesity treatment (GLP-1 analogs, multi-agonists)
• History of prior gastric surgery
• History of gastric or distal esophageal cancer
• History of gastric dysplasia
• Presence of a hiatal hernia > 2 cm
• Contraindication to general anesthesia, including:

• Severe coagulation disorders, including uncontrolled congenital or acquired hemostasis disorders, severe thrombocytopenia (platelets < 50 G/L), non-interruptible anticoagulant or antiplatelet therapy according to current guidelines, uncorrected INR > 1.5
• Hemodynamic instability, defined as persistent hypotension or shock, uncontrolled cardiac arrhythmias, or need for vasopressor support
• Decompensated cardiac disease, including uncontrolled heart failure (NYHA III-IV), unstable ischemic heart disease or recent acute coronary syndrome, untreated severe valvular disease, uncontrolled severe hypertension
• Decompensated respiratory disease, including acute or severe chronic respiratory failure not stabilized, uncontrolled severe COPD, untreated severe obstructive sleep apnea, persistent hypoxemia requiring high-flow oxygen therapy
• Any other clinical condition considered incompatible with general anesthesia or endoscopy by the anesthesiologist or investigator, according to current guidelines and patient safety considerations Significant or unstable renal insufficiency, or history of severe reaction to iodinated contrast agents
• Participation in another clinical research study, except for non-interventional studies
• Patient under legal protection (guardianship, curatorship, or judicial protection)
• Physical inability to provide written informed consent
• Rare forms of obesity of genetic and/or central origin (e.g., associated with craniopharyngioma)
• Pregnancy or breastfeeding
• State medical aid (AME)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• Bichat hospital — Paris

Identifiers

NCT: NCT07576777 · APHP251929

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗