Obesity, Obesity (Body Mass Index >30 kg/m2)
Conditions
Keywords
Obesity, Diabetes Mellitus, MASH, Circulation Disorder, Diabetes Prevention, Type 2 Diabetes (Adult Onset), Vascular Disease, Liver Diseases
Brief summary
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.
Detailed description
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
PROCEDUREEndoscopic Sleeve Gastroplasty (ESG)
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.
PROCEDUREFundal Mucosal Ablation
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.
Sponsors
West Virginia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage Change in Total Body Weight (%TBWL) from baseline to 1 month | Baseline to 1 month |
| Percentage Change in Total Body Weight (%TBWL) from baseline to 3 month | Baseline to 3 month |
| Percentage Change in Total Body Weight (%TBWL) from baseline to 6 month | Baseline to 6 month |
| Percentage Change in Total Body Weight (%TBWL) from baseline to 9 month | Baseline to 9 month |
| Percentage Change in Total Body Weight (%TBWL) from baseline to 12 month | Baseline to 12 month |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent change in Excess Weight Loss (%EWL) from baseline to 1 month | Baseline to 1 month | — |
| Percent change in Excess Weight Loss (%EWL) from baseline to 3 month | Baseline to 3 month | — |
| Percent change in Excess Weight Loss (%EWL) from baseline to 6 month | Baseline to 6 month | — |
| Percent change in Excess Weight Loss (%EWL) from baseline to 9 month | Baseline to 9 month | — |
| Percent change in Excess Weight Loss (%EWL) from baseline to 12 month | Baseline to 12 month | — |
| Number of Participants With Procedure-Related Adverse Events (1 Month) | Up to 1 month after procedure | — |
| Number of Participants With Procedure-Related Adverse Events (3 Month) | Up to 3 month after procedure | — |
| Number of Participants With Procedure-Related Adverse Events (6 Month) | Up to 6 month after procedure | — |
| Number of Participants With Procedure-Related Adverse Events (9 Month) | Up to 9 month after procedure | — |
| Number of Participants With Procedure-Related Adverse Events (12 Month) | Up to 12 month after procedure | — |
| Change in Serum Ghrelin level from baseline to 1 month | Baseline to 1 month | — |
| Change in Serum Ghrelin level from baseline to 6 month | Baseline to 6 month | — |
| Change in Serum Ghrelin level from baseline to 12 month | Baseline to 12 month | — |
| Change in Systolic Blood Pressure from Baseline to 1 Month | Baseline to 1 month | Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Diastolic Blood Pressure from Baseline to 1 Month | Baseline to 1 month | Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Systolic Blood Pressure from Baseline to 3 Months | Baseline to 3 months | Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Diastolic Blood Pressure from Baseline to 3 Months | Baseline to 3 months | Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Systolic Blood Pressure from Baseline to 6 Months | Baseline to 6 months | Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Diastolic Blood Pressure from Baseline to 6 Months | Baseline to 6 months | Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Systolic Blood Pressure from Baseline to 9 Months | Baseline to 9 months | Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Diastolic Blood Pressure from Baseline to 9 Months | Baseline to 9 months | Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Systolic Blood Pressure from Baseline to 12 Months | Baseline to 12 months | Systolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Diastolic Blood Pressure from Baseline to 12 Months | Baseline to 12 months | Diastolic blood pressure will be measured in millimeters of mercury (mmHg) using a standardized blood pressure measurement procedure. |
| Change in Fasting Plasma Glucose from Baseline to 1 Month | Baseline to 1 month | Fasting plasma glucose concentration will be measured in milligrams per deciliter (mg/dL). |
| Change in Fasting Plasma Glucose from Baseline to 6 Months | Baseline to 6 months | Fasting plasma glucose concentration will be measured in milligrams per deciliter (mg/dL). |
| Change in Fasting Plasma Glucose from Baseline to 12 Months | Baseline to 12 months | Fasting plasma glucose concentration will be measured in milligrams per deciliter (mg/dL). |
| Change in Fasting Serum Insulin Concentration from Baseline to 1 Month | Baseline to 1 month | Fasting serum insulin concentration will be measured in milli-international units per milliliter (mIU/mL). |
| Change in Fasting Serum Insulin Concentration from Baseline to 6 Months | Baseline to 6 months | Fasting serum insulin concentration will be measured in milli-international units per milliliter (mIU/mL). |
| Change in Fasting Serum Insulin Concentration from Baseline to 12 Months | Baseline to 12 months | Fasting serum insulin concentration will be measured in milli-international units per milliliter (mIU/mL). |
| Change in Hemoglobin A1c (HbA1c) from Baseline to 1 Month | Baseline to 1 month | HbA1c will be measured as a percentage (%) of total hemoglobin. |
| Change in Hemoglobin A1c (HbA1c) from Baseline to 6 Months | Baseline to 6 months | HbA1c will be measured as a percentage (%) of total hemoglobin. |
| Change in Hemoglobin A1c (HbA1c) from Baseline to 12 Months | Baseline to 12 months | HbA1c will be measured as a percentage (%) of total hemoglobin. |
| Change in Total Cholesterol from Baseline to 1 Month | Baseline to 1 month | Total cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in Total Cholesterol from Baseline to 6 Months | Baseline to 6 months | Total cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in Total Cholesterol from Baseline to 12 Months | Baseline to 12 months | Total cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in Low-Density Lipoprotein (LDL) Cholesterol from Baseline to 1 Month | Baseline to 1 month | Low-density lipoprotein (LDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in Low-Density Lipoprotein (LDL) Cholesterol from Baseline to 6 Months | Baseline to 6 months | Low-density lipoprotein (LDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in Low-Density Lipoprotein (LDL) Cholesterol from Baseline to 12 Months | Baseline to 12 months | Low-density lipoprotein (LDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in High-Density Lipoprotein (HDL) Cholesterol from Baseline to 1 Month | Baseline to 1 month | High-density lipoprotein (HDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in High-Density Lipoprotein (HDL) Cholesterol from Baseline to 6 Months | Baseline to 6 months | High-density lipoprotein (HDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in High-Density Lipoprotein (HDL) Cholesterol from Baseline to 12 Months | Baseline to 12 months | High-density lipoprotein (HDL) cholesterol concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in Triglycerides from Baseline to 1 Month | Baseline to 1 month | Serum triglyceride concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in Triglycerides from Baseline to 6 Months | Baseline to 6 months | Serum triglyceride concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in Triglycerides from Baseline to 12 Months | Baseline to 12 months | Serum triglyceride concentration will be measured from fasting blood samples and in milligrams per deciliter (mg/dL). |
| Change in Hepatic Steatosis Index (HSI) from Baseline to 1 Month | 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. |
| Change in Hepatic Steatosis Index (HSI) from Baseline to 6 Months | 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. |
| Change in Hepatic Steatosis Index (HSI) from Baseline to 12 Months | 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. |
| Change in Liver Stiffness Measurement from Baseline to 1 Month | 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. |
| Change in Liver Stiffness Measurement from Baseline to 6 Months | 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. |
| Change in Liver Stiffness Measurement from Baseline to 12 Months | 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. |
| Change in Quality of Life Score from Baseline to 1 Month | 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. |
| Change in Quality of Life Score from Baseline to 3 Months | 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. |
| Change in Quality of Life Score from Baseline to 6 Months | 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. |
| Change in Quality of Life Score from Baseline to 12 Months | 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. |
Countries
United States
Contacts
CONTACTZim Warda Hasan
PRINCIPAL_INVESTIGATORShailendra Singh, MD, FASGE
West Virginia University
Outcome results
None listed