ENLIGHT Trial: ESG With Fundal Mucosal Ablation

N/ANot Yet RecruitingNCT07792226

West Virginia University62 enrolled

Overview

The ENLIGHT Trial is a single-center, randomized controlled trial evaluating whether adding fundal mucosal ablation (FMA) to endoscopic sleeve gastroplasty (ESG) improves weight loss and metabolic outcomes in adults with obesity. ESG reduces stomach volume through endoscopic suturing, while FMA uses Hybrid Argon Plasma Coagulation to ablate ghrelin-producing mucosa in the gastric fundus, potentially reducing hunger and improving satiety. Because previous ESG with FMA studies were small and single-arm, this trial is designed to provide comparative evidence against ESG alone. Eligible adults aged 18 years or older with a BMI of at least 30 kg/m² and a history of unsuccessful weight-loss attempts will be enrolled. Participants will be randomized on the procedure day to either ESG with FMA or standard ESG alone. The ENLIGHT Trial is a single-center, randomized controlled trial evaluating whether adding fundal mucosal ablation (FMA) to endoscopic sleeve gastroplasty (ESG) improves weight loss and metabolic outcomes in adults with obesity. ESG reduces stomach volume through endoscopic suturing, while FMA uses Hybrid Argon Plasma Coagulation to ablate ghrelin-producing mucosa in the gastric fundus, potentially reducing hunger and improving satiety. Because previous ESG with FMA studies were small and single-arm, this trial is designed to provide comparative evidence against ESG alone. Eligible adults aged 18 years or older with a BMI of at least 30 kg/m² and a history of unsuccessful weight-loss attempts will be enrolled. Participants will be randomized 1:1 on the procedure day to either ESG with FMA or standard ESG alone. The primary outcome is the difference between groups in percentage total body weight loss at 12 months. Secondary outcomes include percent excess weight loss, fasting ghrelin levels, blood pressure and antihypertensive medication use, lipid profile, fasting glucose, insulin, HbA1c, insulin resistance, hepatic steatosis and fibrosis measures, quality of life, pain, gastric symptoms, appetite and eating behavior, and the frequency and severity of adverse events.

Obesity is associated with a number of chronic health conditions, including type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, obstructive sleep apnea, and metabolic liver disease. Treatment options include lifestyle modification, anti-obesity medications, bariatric surgery, and endoscopic weight-loss procedures. ESG is an endoscopic procedure in which full-thickness sutures are placed to reduce the volume and length of the stomach and create a sleeve-like configuration. The gastric fundus is generally preserved during ESG. Although ESG has been shown to produce clinically meaningful weight loss, weight loss following ESG is generally less than that achieved with surgical sleeve gastrectomy. One possible explanation for this difference is the role of the gastric fundus in appetite regulation. The fundus contains a large number of cells that produce ghrelin, a hormone involved in hunger and food intake. Procedures that remove or alter the gastric fundus may reduce circulating ghrelin levels. Fundal mucosal ablation (FMA) is an emerging endoscopic technique designed to treat the mucosal lining of the gastric fundus while preserving the stomach itself. Early studies have suggested that FMA may reduce fasting ghrelin levels and may contribute to reductions in hunger and body weight. The ENLIGHT trial is designed to determine whether adding FMA to standard ESG provides additional benefit compared with ESG alone. Participants assigned to the ESG group will undergo standard ESG under general anesthesia. Participants assigned to the ESG with FMA group will undergo standard ESG together with FMA during the same procedure. Following the procedure, participants in both groups will receive similar standard post-procedure care. Participants will be followed for approximately 52 weeks after the procedure. Study Significance The ENLIGHT Trial is intended to provide comparative evidence regarding whether adding FMA to ESG improves weight loss while maintaining an acceptable safety and tolerability profile. The study will also help determine whether the combined procedure has additional effects on metabolic health, obesity-related conditions, patient-reported outcomes, and fasting ghrelin levels.

Interventions

Endoscopic Sleeve Gastroplasty (ESG)PROCEDURE

Endoscopic sleeve gastroplasty (ESG) is performed under general anesthesia using a flexible endoscope and full-thickness endoscopic suturing. Sutures are placed along the greater curvature of the stomach to create a smaller, sleeve-like gastric configuration while preserving the gastric fundus. The procedure is intended to reduce gastric volume, promote earlier satiety, and support weight loss.

Fundal Mucosal AblationPROCEDURE

Fundal mucosal ablation is performed during the same procedural session as endoscopic sleeve gastroplasty. The gastric fundal mucosa is lifted using a submucosal injection of saline and methylene blue and then treated with controlled Hybrid Argon Plasma Coagulation. The procedure is intended to ablate superficial ghrelin-producing mucosa in the gastric fundus, potentially reducing hunger and supporting weight loss.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female subjects aged ≥18 years 2. Subjects with a BMI ≥30 kg/m² 3. Subjects have a history of failure of at least one prior weight loss attempt, including but not limited to dietary modification, physical exercise, behavioral modification, pharmacologic therapy (alone or in combination), or other non-surgical weight reduction methods. 4. Willing and able to comply with all study requirements, including but not limited to signing a written informed consent form prior to participation, routine follow-up visit schedule, completing all required laboratory, imaging, and additional assessments, and participating in dietary counseling sessions. 5. Women of childbearing potential (i.e., not postmenopausal and not surgically sterilized) must agree to use adequate and effective contraception methods throughout the study period. 6. Able to travel to visit the study site and have access to the internet to facilitate remote follow-up activities, as applicable. Exclusion Criteria: 1. Prior gastric or bariatric surgery/procedure that may affect the anatomy or feasibility of the intervention, (e.g; prior Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, endoscopic sleeve gastroplasty). 2. Clinically significant structural abnormality that may increase procedural risk or interfere with endoscopic access 3. Conditions associated with increased bleeding (e.g., severe coagulopathy, severe immunocompromise). 4. Conditions that may affect weight, eating behavior, (e.g; GI motility disorders, gastroparesis, chronic abdominal pain, eating disorders, or active psychological conditions). 5. Pregnancy, breastfeeding, or any other condition that, in the opinion of the investigator or treating physician, would make participation unsafe or interfere with study procedures. 6. Other cases deemed by the examining physician as unsuitable for safe treatment.

Outcomes

Primary Outcomes

Percentage Change in Total Body Weight (%TBWL) from baseline to 1 month

Time frame: Baseline to 1 month

Percentage Change in Total Body Weight (%TBWL) from baseline to 3 month

Time frame: Baseline to 3 month

Percentage Change in Total Body Weight (%TBWL) from baseline to 6 month

Time frame: Baseline to 6 month

Percentage Change in Total Body Weight (%TBWL) from baseline to 9 month

Time frame: Baseline to 9 month

Percentage Change in Total Body Weight (%TBWL) from baseline to 12 month

Time frame: Baseline to 12 month

Secondary Outcomes

Percent change in Excess Weight Loss (%EWL) from baseline to 1 month

Time frame: Baseline to 1 month

Percent change in Excess Weight Loss (%EWL) from baseline to 3 month

Time frame: Baseline to 3 month

Percent change in Excess Weight Loss (%EWL) from baseline to 6 month

Time frame: Baseline to 6 month

Percent change in Excess Weight Loss (%EWL) from baseline to 9 month

Time frame: Baseline to 9 month

Percent change in Excess Weight Loss (%EWL) from baseline to 12 month

Time frame: Baseline to 12 month

Number of Participants With Procedure-Related Adverse Events (1 Month)

Time frame: Up to 1 month after procedure

Number of Participants With Procedure-Related Adverse Events (3 Month)

Time frame: Up to 3 month after procedure

Number of Participants With Procedure-Related Adverse Events (6 Month)

Time frame: Up to 6 month after procedure

Number of Participants With Procedure-Related Adverse Events (9 Month)

Time frame: Up to 9 month after procedure

Number of Participants With Procedure-Related Adverse Events (12 Month)

Time frame: Up to 12 month after procedure

Change in Serum Ghrelin level from baseline to 1 month

Time frame: Baseline to 1 month

Change in Serum Ghrelin level from baseline to 6 month

Time frame: Baseline to 6 month

Change in Serum Ghrelin level from baseline to 12 month

Time frame: Baseline to 12 month

Change in Systolic Blood Pressure from Baseline to 1 Month

Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 1 month

Change in Diastolic Blood Pressure from Baseline to 1 Month

Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 1 month

Change in Systolic Blood Pressure from Baseline to 3 Months

Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 3 months

Change in Diastolic Blood Pressure from Baseline to 3 Months

Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 3 months

Change in Systolic Blood Pressure from Baseline to 6 Months

Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 6 months

Change in Diastolic Blood Pressure from Baseline to 6 Months

Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 6 months

Change in Systolic Blood Pressure from Baseline to 9 Months

Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 9 months

Change in Diastolic Blood Pressure from Baseline to 9 Months

Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 9 months

Change in Systolic Blood Pressure from Baseline to 12 Months

Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 12 months

Change in Diastolic Blood Pressure from Baseline to 12 Months

Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure.

Time frame: Baseline to 12 months

Change in Fasting Plasma Glucose from Baseline to 1 Month

Fasting plasma glucose concentration will be measured in milligrams per deciliter (mg/dL).

Time frame: Baseline to 1 month

Change in Fasting Plasma Glucose from Baseline to 6 Months

Fasting plasma glucose concentration will be measured in milligrams per deciliter (mg/dL).

Time frame: Baseline to 6 months

Change in Fasting Plasma Glucose from Baseline to 12 Months

Fasting plasma glucose concentration will be measured in milligrams per deciliter (mg/dL).

Time frame: Baseline to 12 months

Change in Fasting Serum Insulin Concentration from Baseline to 1 Month

Fasting serum insulin concentration will be measured in milli-international units per milliliter (mIU/mL).

Time frame: Baseline to 1 month

Change in Fasting Serum Insulin Concentration from Baseline to 6 Months

Fasting serum insulin concentration will be measured in milli-international units per milliliter (mIU/mL).

Time frame: Baseline to 6 months

Change in Fasting Serum Insulin Concentration from Baseline to 12 Months

Fasting serum insulin concentration will be measured in milli-international units per milliliter (mIU/mL).

Time frame: Baseline to 12 months

Change in Hemoglobin A1c (HbA1c) from Baseline to 1 Month

HbA1c will be measured as a percentage (%) of total hemoglobin.

Time frame: Baseline to 1 month

Change in Hemoglobin A1c (HbA1c) from Baseline to 6 Months

HbA1c will be measured as a percentage (%) of total hemoglobin.

Time frame: Baseline to 6 months

Change in Hemoglobin A1c (HbA1c) from Baseline to 12 Months

HbA1c will be measured as a percentage (%) of total hemoglobin.

Time frame: Baseline to 12 months

Change in Total Cholesterol from Baseline to 1 Month

Total cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 1 month

Change in Total Cholesterol from Baseline to 6 Months

Total cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 6 months

Change in Total Cholesterol from Baseline to 12 Months

Total cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 12 months

Change in Low-Density Lipoprotein (LDL) Cholesterol from Baseline to 1 Month

Low-density lipoprotein (LDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 1 month

Change in Low-Density Lipoprotein (LDL) Cholesterol from Baseline to 6 Months

Low-density lipoprotein (LDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 6 months

Change in Low-Density Lipoprotein (LDL) Cholesterol from Baseline to 12 Months

Low-density lipoprotein (LDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 12 months

Change in High-Density Lipoprotein (HDL) Cholesterol from Baseline to 1 Month

High-density lipoprotein (HDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 1 month

Change in High-Density Lipoprotein (HDL) Cholesterol from Baseline to 6 Months

High-density lipoprotein (HDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 6 months

Change in High-Density Lipoprotein (HDL) Cholesterol from Baseline to 12 Months

High-density lipoprotein (HDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 12 months

Change in Triglycerides from Baseline to 1 Month

Serum triglyceride concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 1 month

Change in Triglycerides from Baseline to 6 Months

Serum triglyceride concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 6 months

Change in Triglycerides from Baseline to 12 Months

Serum triglyceride concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL).

Time frame: Baseline to 12 months

Change in Hepatic Steatosis Index (HSI) from Baseline to 1 Month

HSI is a calculated score used to estimate the likelihood of hepatic steatosis. Higher scores indicate a greater likelihood of hepatic steatosis.

Time frame: Baseline to 1 month

Change in Hepatic Steatosis Index (HSI) from Baseline to 6 Months

HSI is a calculated score used to estimate the likelihood of hepatic steatosis. Higher scores indicate a greater likelihood of hepatic steatosis.

Time frame: Baseline to 6 months

Change in Hepatic Steatosis Index (HSI) from Baseline to 12 Months

HSI is a calculated score used to estimate the likelihood of hepatic steatosis. Higher scores indicate a greater likelihood of hepatic steatosis.

Time frame: Baseline to 12 months

Change in Liver Stiffness Measurement from Baseline to 1 Month

Liver fibrosis will be assessed by FibroScan. Liver stiffness will be measured in kilopascals (kPa), with higher liver stiffness values indicating greater liver fibrosis.

Time frame: Baseline to 1 month

Change in Liver Stiffness Measurement from Baseline to 6 Months

Liver fibrosis will be assessed by FibroScan. Liver stiffness will be measured in kilopascals (kPa), with higher liver stiffness values indicating greater liver fibrosis.

Time frame: Baseline to 6 months

Change in Liver Stiffness Measurement from Baseline to 12 Months

Liver fibrosis will be assessed by FibroScan. Liver stiffness will be measured in kilopascals (kPa), with higher liver stiffness values indicating greater liver fibrosis.

Time frame: Baseline to 12 months

Change in Quality of Life Score from Baseline to 1 Month

Health-related quality of life will be assessed using the 36-Item Short Form Health Survey (SF-36). Scores range from 0 to 100, with higher scores indicating better health-related quality of life.

Time frame: Baseline to 1 month

Change in Quality of Life Score from Baseline to 3 Months

Health-related quality of life will be assessed using the 36-Item Short Form Health Survey (SF-36). Scores range from 0 to 100, with higher scores indicating better health-related quality of life.

Time frame: Baseline to 3 months

Change in Quality of Life Score from Baseline to 6 Months

Health-related quality of life will be assessed using the 36-Item Short Form Health Survey (SF-36). Scores range from 0 to 100, with higher scores indicating better health-related quality of life.

Time frame: Baseline to 6 months

Change in Quality of Life Score from Baseline to 12 Months

Health-related quality of life will be assessed using the 36-Item Short Form Health Survey (SF-36). Scores range from 0 to 100, with higher scores indicating better health-related quality of life.

Time frame: Baseline to 12 months

ENLIGHT Trial: ESG With Fundal Mucosal Ablation

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts