Endoscopic Gastric Mucosal Ablation as a Primary Obesity Therapy (COMET)

Endoscopic Gastric Mucosal Ablation (GMA) as a Primary Obesity Therapy Early Feasibility [COMET EF] - Step II

This study is intended to investigate safety and feasibility of a new weight loss technique called endoscopic Gastric Mucosal Ablation (GMA) that does not require surgery, but can be achieved using an endoscopic procedure.

Previous studies have suggested that weight loss after vertical sleeve gastrectomy (VSG) is partly due to the removal of normal stomach tissue suspected of having hormonal function. The study will investigate the minimally invasive treatment of obesity by means of argon plasma coagulation (APC) in combination with waterjet submucosal injection using HybridAPC.

As primary objective total body weight loss (TBWL) will be determined as body weight difference at the 6 months follow up (FU) visit after the last treatment session in comparison to the body weight prior to the initial treatment.

After signing the informed consent the doctor and research team will determine if the participant meets all requirements for this study. If a participant is confirmed to be a suitable candidate additional tests will be performed prior to the first application of GMA to assess the health status of the participant prior to treatment. During the screening and baseline visit the medical history and the medications of the participant will be reviewed.

After the treatments the participants will be followed for up to 12 months to assess the outcome of the GMA procedure.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Adiposity
• Intervention / Treatment: Device: Hybrid Argon Plasma Coagulation (HAPC)

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jan Miller, RN, CCRA; Phone Number: 344 800-778-3723; Email: jan.miller@erbe-usa.com
• Study Contact Backup: Name: Hartmut Hahn, Dr.rer.nat.; Phone Number: +497071755225; Email: hartmut.hahn@erbe-med.com

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic
      • Contact: Dilhana Badurdeen, MBBS
  • North Carolina
    • Cary, North Carolina, United States, 27513
      • Recruiting
      • True You Weight Loss
      • Contact: Christopher McGowan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or females patients in the range of class I to class III obesity (BMI ≥ 30 to ≤ 40 with obesity-related comorbidity or BMI > 40 to BMI ≤ 45).
2. Age 22 - 60 yrs.
3. Treatment naïve for bariatric surgery or endoscopic bariatric therapy
4. Agree to avoid any use of weight loss medications such as Meridia, Saxenda, Januvia, Xenical, Duromine or over the counter weight loss medications or supplements throughout the study.
5. Women of childbearing potential (WOCBP) must agree to use acceptable contraception methods.
6. Agree not to donate blood during their participation in the study.
7. Able to comply with study requirements and understand and sign the Informed Consent Form.
8. Stable weight defined as a fluctuation of less than 5% for at least 3 months prior to screening visit.
9. History of failure to lose weight using conventional diet and lifestyle therapies.

Exclusion Criteria:

1. Patients requiring exogenous insulin.
2. HbA1c > 8.5 %
3. Pregnant or breast-feeding or intending to get pregnant during the study.
4. Unwilling or unable to complete the Visual Analogue Scale for pain assessment, patient questionnaires, or comply with study visits and other study procedures as required per protocol.
5. History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
6. Probable insulin production failure, defined as fasting C-Peptide serum < 1 ng/mL (333 pmol/l).
7. Previous use of any types of insulin for > 1 month (at any time, except for treatment of gestational diabetes).
8. Change in diabetic treatment within the last three months.
9. Use of glucose-lowering drugs for diabetes mellitus treatment with the exception of sulfonylurea (SU), biguanides and sodium dependent glucose co-transporter 2 (SGLT-2) inhibitors.
10. Change of diabetes medication or doses 12 weeks prior to screening visit.
11. Hypoglycemia unawareness or a history of severe hypoglycemia (more than 1 severe hypoglycemic event, as defined by need for third-party-assistance, in the last year).
12. Known autoimmune disease, including but not limited to celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder.
13. Previous upper GI surgery, or other endoscopic bariatric procedures or conditions, prior intra-gastric balloon or another gastric implant.
14. History of diabetic gastroparesis.
15. Known active hepatitis or active liver disease.
16. Acute gastrointestinal illness in the previous 7 days.
17. Known history irritable bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease.
18. Known history of a structural or functional disorder of the esophagus that may impede passage of the device through the gastrointestinal tract or increase risk of esophageal damage during an endoscopic procedure, including Barrett's esophagus, esophagitis, dysphagia, achalasia, stricture/stenosis, esophageal varices, esophageal diverticula, esophageal perforation, or any other disorder of the esophagus.
19. Known history of a structural or functional disorder of the esophagus, including any swallowing disorder, esophageal chest pain disorders, or drug refractory esophageal reflux symptoms.
20. Known history of a structural or functional disorder of the stomach including gastroparesis, gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (>3 cm), cancer or any other disorder of the stomach.
21. Known history of chronic symptoms suggestive of a structural or functional disorder of the stomach, including any symptoms of chronic upper abdominal pain, chronic nausea, chronic vomiting, chronic dyspepsia or symptoms suggestive of gastroparesis, including post-prandial fullness or pain, post-prandial nausea or vomiting or early satiety.
22. Currently have ongoing symptoms suggestive of intermittent small bowel obstruction, such as recurrent bouts of post-prandial abdominal pain, nausea or vomiting.
23. Active H. pylori infection (Subjects with active H. pylori may continue with the screening process if they are treated with an appropriate antibiotic regimen, and eradication has been confirmed).
24. History of coagulopathy, upper gastrointestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia.
25. Current use of anticoagulation therapy
26. Obligate use of anti-inflammatory drugs that cannot be suspended for a minimum of 4 weeks post procedure
27. Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
28. Use of drugs known to affect GI motility (e.g. Metoclopramide).
29. Receiving any weight loss medications such as Meridia, Xenical, Saxenda, Januvia, Duromine or over the counter weight loss medications at screening.
30. Untreated/inadequately treated hypothyroidism, defined as an elevated Thyroid-Stimulating Hormone (TSH) level at Screening; if on thyroid hormone replacement therapy, must be on stable dose for at least 6 weeks prior to Screening.
31. Persistent Anemia, defined as Hemoglobin <10 g/dL.
32. Significant cardiovascular disease including known history of valvular disease, or myocardial infarction, heart failure, transient ischemic attack or stroke within the last 6 months.
33. Known moderate or severe chronic kidney disease (CKD), with estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2 (estimated by MDRD).
34. Known immunocompromised status, including but not limited to individuals who have undergone organ transplantation, chemotherapy or radiotherapy within the past 12 months, who have clinically-significant leukopenia, who are positive for the human immunodeficiency virus (HIV) or whose immune status makes the subject a poor candidate for clinical trial participation in the opinion of the Investigator.
35. Active systemic infection.
36. Known active malignancy within the last 5 years (with the exception of treated basal cell or treated squamous cell carcinoma).
37. Subjects with an established diagnosis of Multiple Endocrine Neoplasia syndrome type 1.
38. Not a candidate for surgery or general anesthesia.
39. Active illicit substance abuse or alcoholism.
40. Current smoker or smoking history in the last six months.
41. Participating in another ongoing clinical trial of an investigational drug or device.
42. Any other mental or physical condition which, in the opinion of the investigator, makes the subject a poor candidate for clinical trial participation.
43. Other medical condition that does not allow for endoscopic procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Gastric mucosal ablation; Participants receive submucosal injection followed by ablation of gastric mucosa using Hybrid Argon Plasma Coagulation (HAPC)	Device: Hybrid Argon Plasma Coagulation (HAPC); Gastric mucosal ablation is an endoscopic procedure which uses argonplasma coagulation in combination with submucosal injection to achieve selective ablation to the gastric mucosa and preventing thermal damage to the muscle layer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total body weight loss	Primary endpoint will be determined as the % of total body weight loss (TBWL). Total body weight loss (TBWL) will be determined as body weight difference at the final 6 months follow up (FU) visit after the last treatment visit in comparison to the body weight prior to the first treatment.	9 months

Collaborators and Investigators

• Sponsor: Erbe Elektromedizin GmbH
• Collaborators: Erbe USA Incorporated
• Investigators: Principal Investigator: Dilhana Badurdeen, MBBS, Mayo Clinic, Jacksonville, Florida

Publications and helpful links

General Publications

• Oberbach A, Schlichting N, Heinrich M, Kullnick Y, Retschlag U, Lehmann S, Khashab MA, Kalloo AN, Kumbhari V. Gastric mucosal devitalization reduces adiposity and improves lipid and glucose metabolism in obese rats. Gastrointest Endosc. 2018 Jan;87(1):288-299.e6. doi: 10.1016/j.gie.2017.04.038. Epub 2017 May 4.
• Kumbhari V, Lehmann S, Schlichting N, Heinrich M, Kullnick Y, Retschlag U, Enderle M, Dietrich A, Khashab MA, Kalloo AN, Oberbach A. Gastric mucosal devitalization is safe and effective in reducing body weight and visceral adiposity in a porcine model. Gastrointest Endosc. 2018 Jul;88(1):175-184.e1. doi: 10.1016/j.gie.2018.02.022. Epub 2018 Feb 22.
• Fayad L, Oberbach A, Schweitzer M, Askin F, Voltaggio L, Larman T, Enderle M, Hahn H, Khashab MA, Kalloo AN, Kumbhari V. Gastric mucosal devitalization (GMD): translation to a novel endoscopic metabolic therapy. Endosc Int Open. 2019 Dec;7(12):E1640-E1645. doi: 10.1055/a-0957-3067. Epub 2019 Nov 25.
• Oberbach A, Schlichting N, Kullnick Y, Heinrich M, Lehmann S, Retschlag U, Friedrich M, Fayad L, Dietrich A, Khashab MA, Kalloo AN, Kumbhari V. Gastric mucosal devitalization improves blood pressure, renin and cardiovascular lipid deposition in a rat model of obesity. Endosc Int Open. 2019 Dec;7(12):E1605-E1615. doi: 10.1055/a-0990-9683. Epub 2019 Nov 25.
• Itani MI, Oberbach A, Salimian KJ, Enderle M, Hahn H, Abbarh S, Kendrick K, Schlichting N, Anders RA, Besharati S, Farha J, Fayad L, Kalloo AN, Badurdeen D, Kumbhari V. Gastric Mucosal Devitalization (GMD): Using the Porcine Model to Develop a Novel Endoscopic Bariatric Approach. Obes Surg. 2022 Feb;32(2):381-390. doi: 10.1007/s11695-021-05773-4. Epub 2021 Nov 19.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: August 1, 2022
• First Submitted That Met QC Criteria: August 1, 2022
• First Posted (Actual): August 3, 2022

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Endoscopic bariatric therapy; Hybrid Argon Plasma Coagulation
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: GMA_2022_01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes