Multicenter Endoscopic Sleeve Gastrectomy (ESG) Trial (MERIT Trial)

Study Overview
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Brief Summary
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Endoscopic Sleeve Gastroplasty (ESG) is an endoscopic minimally invasive weight loss procedure where a commercially available, FDA approved, full-thickness endoscopic suturing device (Overstitch; Apollo Endosurgery, Austin, TX) is used to reduce the stomach volume by 80% through the creation of a restrictive endoscopic sleeve. This is accomplished by a series of endoscopically placed full-thickness sutures through the gastric wall, extending from the antrum to the gastroesophageal junction. Up to 200 participants at 9 locations in the United States will participate in this study. The ESG procedure has been performed clinically since 2013 in the United States. The investigators are completing this study to compare how effective the ESG is for achieving long-term weight loss when compared to lifestyle modification only, as well as to evaluate the long-term safety and durability of the procedure and its impact on quality of life. Results of this research may help support having this procedure covered by health insurance plans for future patients.

Official Title
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Multi-center ESG Randomized Interventional Trial (MERIT-Trial)

Conditions
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Obesity, Hypertension, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Device: Overstitch Endoscopic Suture System
* Behavioral: Lifestyle Intervention


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Age 21-65 BMI ≥ 30 and ≤40 kg/m² Willingness to comply with the substantial lifelong dietary restrictions required by the procedure History of failure with non-surgical weight-loss methods Willingness to follow protocol requirements, including signed informed consent, routine follow-up schedule, completing laboratory tests, and completing diet counseling Residing within a reasonable distance from the investigator's office and able to travel to the investigator to complete all routine follow- up visits Ability to give informed consent Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must agree to use adequate birth control methods ***There will be a quota for at least a) 50 patients with hypertension on one or more anti-hypertensive medication, b) 50 patients with type II diabetes mellitus on oral agents only with HgA1c ≤ 9, and thus the cohort of 200 patients will be stratified into three groups (Obesity, Obesity HTH, Obesity DM) and block randomized. No more than 50 participants without comorbidities will be enrolled in the trial. EXCLUSION CRITERIA History of foregut or gastrointestinal (GI) surgery (except uncomplicated cholecystectomy or appendectomy) Prior gastrointestinal surgery with sequelae, i.e. obstruction, and/or adhesive peritonitis or known abdominal adhesions. Prior open or laparoscopic bariatric surgery. Prior surgery of any kind on the esophagus, stomach or any type of hiatal hernia surgery. Any inflammatory disease of the gastrointestinal tract including esophagitis, Barrett's esophagus, gastric ulceration, duodenal ulceration, cancer or specific inflammation such as Crohn's disease. Potential upper gastrointestinal bleeding conditions such as esophageal or gastric varices, congenital or acquired intestinal telangiectasis, or other congenital anomalies of the gastrointestinal tract such as atresias or stenoses. A gastric mass or gastric polyps > 1 cm in size. A hiatal hernia > 4cm of axial displacement of the z-line above the diaphragm or severe or intractable gastro-esophageal reflux symptoms. A structural abnormality in the esophagus or pharynx such as a stricture or diverticulum that could impede passage of the endoscope. Achalasia or any other severe esophageal motility disorder Severe coagulopathy. Insulin-dependent diabetes (either Type 1 or Type 2) or a significant likelihood of requiring insulin treatment in the following 12 months or a HgbA1C >= 9. Subjects with any serious health condition unrelated to their weight that would increase the risk of endoscopy Chronic abdominal pain Motility disorders of the GI tract such as gross esophageal motility disorders, gastroparesis or intractable constipation Hepatic insufficiency or cirrhosis Use of an intragastric device prior to this study due to the increased thickness of the stomach wall preventing effective suturing. Active psychological issues preventing participation in a life-style modification program as determined by a psychologist Patients unwilling to participate in an established medically-supervised diet and behavior modification program, with routine medical follow-up. Patients receiving daily prescribed treatment with high dose aspirin (> 80mg daily), anti-inflammatory agents, anticoagulants or other gastric irritants. Patients who are unable or unwilling to take prescribed proton pump inhibitor medication Patients who are pregnant or breast-feeding. Subjects with Severe cardiopulmonary disease or other serious organic disease which might include known history of coronary artery disease, Myocardial infarction within the past 6 months, poorly-controlled hypertension, required use of NSAIDs Subjects taking medications on specified hourly intervals that may be affected by changes to gastric emptying, such as anti-seizure or anti-arrhythmic medications Subjects who are taking corticosteroids, immunosuppressants, and narcotics Subjects who are taking diet pills Symptomatic congestive heart failure, cardiac arrhythmia or unstable coronary artery disease. Pre-existing respiratory disease such as chronic obstructive pulmonary disease (COPD), pneumonia or cancer. Diagnosis of autoimmune connective tissue disorder (e.g. lupus, erythematous, scleroderma) or immunocompromised. Specific diagnosed genetic disorder such as Prader Willi syndrome. Eating disorders including night eating syndrome (NES), bulimia, binge eating disorder, or compulsive overeating Known history of endocrine disorders affecting weight such as uncontrolled hypothyroidism.

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Group: Lifestyle Modification<br>Participants randomized to the control group (lifestyle modification only) in Year 1 will undergo a standard moderate intensity life-style intervention during the first 12 months of participation. | Behavioral: Lifestyle Intervention<br>* Standard low-calorie diet plan and moderate intensity life-style intervention of 150 minutes of aerobic exercise per week for 12 months.<br>|
| Experimental: Treatment Group: Overstitch ESG Procedure<br>Participants randomized to the treatment group will proceed to have the Overstitch Endoscopic Sleeve Gastroplasty (ESG) at the start of Year 1 and will undergo a standard moderate intensity life-style intervention during the first 12 months of participation. All patients undergoing ESG will go on a 6 weeks transitional diet.ESG patients will undergo a standard moderate intensity life-style intervention administered over 15 12 visits in the first year after ESG. ESG patients who have not achieved >25% EWL at the end of Year 1 will undergo a repeat upper endoscopy at 52 to 60 weeks to assess the durability of the plications. Patients will continue follow-up with a modified lifestyle intervention program administered over 6 visits in the second year | Device: Overstitch Endoscopic Suture System<br>* Endoscopic Sleeve Gastroplasty (ESG), an endoscopic minimally-invasive weight loss procedure, utilizing a suturing device to reduce the stomach volume by 80% through the creation of sleeve. This is accomplished by a series of endoscopically placed stitches through the stomach wall.<br>Behavioral: Lifestyle Intervention<br>* Standard low-calorie diet plan and moderate intensity life-style intervention of 150 minutes of aerobic exercise per week for 12 months.<br>|
| Experimental: Crossover Group: Lifestyle Intervention to ESG Procedure<br>Control group participants (lifestyle modification only) who were compliant with at least 75% of visits in Year 1, have not achieved ≥25% EWL or have a BMI >30 measured at the week 52 visit, and have no new psychosocial contraindications as deemed by the treatment team to the procedure will cross over to receive the Overstitch ESG in Year 2, in addition to the standard moderate intensity lifestyle intervention program of 12 months. | Device: Overstitch Endoscopic Suture System<br>* Endoscopic Sleeve Gastroplasty (ESG), an endoscopic minimally-invasive weight loss procedure, utilizing a suturing device to reduce the stomach volume by 80% through the creation of sleeve. This is accomplished by a series of endoscopically placed stitches through the stomach wall.<br>Behavioral: Lifestyle Intervention<br>* Standard low-calorie diet plan and moderate intensity life-style intervention of 150 minutes of aerobic exercise per week for 12 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Excess Weight Loss (EWL) | Percentage of excess weight loss in participants at 12 months from randomization. Calculated as (weight loss/baseline excess weight) x 100, where weight loss is defined as follow-up weight minus the initial weight, and baseline excess weight is defined as index weight minus ideal weight X (X=25 kg/m²) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With ≥25% EWL | Total number of participants with ≥25% excess weight loss at 12 months from randomization | 12 months | 
| Number of Participants Off Or With Reduction in Antihypertensive Medications | Total number participants off or with reduction in antihypertensive medications | 12 months | 
| Change in Blood Pressure | Change in blood pressure measured in units of millimeters of mercury (mmHg) | Baseline, 12 months | 
| Change in Blood Pressure for ESG Intervention From Baseline to 24 Months | Change in blood pressure for participants that received ESG intervention measured in units of millimeters of mercury (mmHg) | Baseline, 24 months | 
| Number of Participants Off or With Reduction in Diabetes Medications | Total number of participants off or with reduction in diabetes medications | 12 months | 
| Change in HgbA1c | Change in HgbA1c levels | Baseline, 12 months | 
| Change in HgbA1c for ESG Intervention From Baseline to 24 Months | Change in HgbA1c levels for participants that received the ESG intervention | Baseline, 24 months | 
| Percentage of Total Body Weight Loss (TBWL) | Percentage of total body weight loss in participants | 12 months | 
| Number of Participants to Achieve ≥5% TBWL | Total number of participants to achieve ≥5% total body weight loss | 12 months | 
| Number of Participants to Achieve ≥10% TBWL | Total number of participants to achieve ≥10% total body weight loss | 12 months | 
| Esophagitis at Repeat Endoscopy | Total number of participants to have esophagitis at repeat endoscopy | 12 months | 
| Change in Impact of Weight on Quality of Life-Lite (IWQOL-Lite) | Changes in impact of weight on quality of life score assessed using self-reported IWQOL-lite questionnaire consisting of five domains: physical function (11 items, score range from 11-55 with higher scores indicating more negative outcome), self-esteem (7 items, score range from 7-35 with higher scores indicating more negative outcome), sexual life (4 items, score range from 4-20 with higher scores indicating more negative outcome), public distress (5 items, score range from 5-25 with higher scores indicating more negative outcome), and work (4 items, score range from 4-20 with higher scores indicating more negative outcome). | Baseline, 12 months | 
| Changes in Health Status Survey Scores | Changes in subject's view of health assessed using self-reported SF-36 Health Status Survey consisting of 8 scaled scores: physical function (10-items, score range from 0-100 with higher scores indicating more positive outcome), role limitations due to physical health (4-items, score range from 0-100 with higher scores indicating more positive outcome), role limitations due to emotional problems (3-item, score range from 0-100 with higher scores indicating more positive outcome), energy/fatigue (4-items, score range from 0-100 with higher scores indicating more positive outcome), emotional well-being (5-items, score range from 0-100 with higher scores indicating more positive outcome), social functioning (2-items, score range from 0-100 with higher scores indicating more positive outcome), pain (2-items, score range from 0-100 with higher scores indicating more positive outcome), general health (5-items, score range from 0-100 with higher scores indicating more positive outcome) | Baseline, 12 months | 
| Number of Participants With Major Depression or Severe Major Depression at Baseline | Number of participants to identify with major or severe major depression measured using the self-reported Patient Health Questionnaire (PHQ-9). The PHQ-9 is self-reported 9-item questionnaire to assess degree of depression severity with total score range from 0-27 categories were defined as followed: minimal, score < 10; major depression, 10 ≤ score < 20; severe major depression, x ≥ 20 | Baseline | 
| Number of Participants With Major Depression or Severe Major Depression at 12 Months | Number of participants to identify with major or severe major depression measured using the self-reported Patient Health Questionnaire (PHQ-9). The PHQ-9 is self-reported 9-item questionnaire to assess degree of depression severity with total score range from 0-27 categories were defined as followed: minimal, score < 10; major depression, 10 ≤ score < 20; severe major depression, x ≥ 20 | 12 months | 
| Change in Eating Behaviors | Change in eating behaviors evaluated using the self-reported Three Factor Eating Questionnaire (TFEQ) consisting of 3 domains: cognitive restraint (6-items, score range from 0-100 with higher score indicating more restraint), uncontrolled eating (9-items, score range from 0-100 with lower score indicating more control), and emotional eating (3-items, score range 0-100 with higher score indicating eating with negative emotions) | Baseline, 12 months |