Effect of Duodenal Mucosal Resurfacing (DMR) Using the Revita System in the Treatment of Type 2 Diabetes (T2D)

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy and safety of the Fractyl duodenal mucosal resurfacing (DMR) Procedure using the Revita System compared to a sham procedure for the treatment of uncontrolled type 2 diabetes. Subjects randomized to the DMR procedure are followed per protocol for 48 Weeks. The Sham treatment arm will cross over to receive the DMR treatment at 24 weeks with background medications held constant from 24-48 weeks of follow up.

Detailed Description
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The study is a multi-center, randomized, prospective, double-blinded (subject and endocrinologist) trial of type 2 diabetes patients sub-optimally controlled on 1 or more oral anti-diabetic medications comparing the Fractyl DMR procedure to sham procedure. Randomization will be 1:1 DMR treatment to sham. All subjects will participate in a 4 week oral anti-diabetic medication run-in period before the index procedure to confirm lack of blood glucose control in conjunction with medication compliance and nutritional counseling. The Sham treatment arm will cross-over to receive the DMR treatment at 24 weeks with background medications held constant 24weeks of follow up after the cross-over DMR procedure. The DMR treatment arm will be managed according to current diabetes standard of care. Subjects randomized to the DMR procedure are followed per protocol for 48 Weeks. The Sham treatment arm will cross over to receive the DMR treatment at 24 weeks with background medications held constant from 24-48 weeks of follow up.

Official Title
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Evaluation of the Effect of Duodenal Mucosal Resurfacing (DMR) Using the Revita System in the Treatment of Type 2 Diabetes (T2D)

Conditions
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Diabetes Mellitus, Type 2, Noninsulin-Dependent Diabetes Mellitus

Intervention / Treatment
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* Procedure: DMR Procedure
* Procedure: Sham Procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 28-75 years of age Diagnosed with Type 2 Diabetes and evidence of preserved insulin secretion. Fasting insulin > 7 μU/ mL. Glycated Hemoglobin (HbA1c) of 7.5 - 10.0% (59-86 mmol/mol) Body Mass Index (BMI) ≥ 24 and ≤ 40 kg/m2 Currently taking one or more oral glucose lowering medications of which one must be Metformin, with no changes in dose or medication in the previous 12 Weeks prior to study entry Able to comply with study requirements and understand and sign the informed consent Exclusion Criteria: Diagnosed with Type 1 Diabetes or with a history of ketoacidosis Current use of Insulin Current use of Glucagon-like peptide-1 (GLP-1) analogues 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) Known autoimmune disease, as evidenced by a positive Anti- Glutamic Acid Decarboxylase (GAD) test, including Celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder Active H. pylori infection (Participants with active H. pylori may continue with the screening process if they are treated via medication and re-testing verifies the condition has resolved.) Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions History of chronic or acute pancreatitis Known active hepatitis or active liver disease Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn's Disease and Celiac Disease History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia Use of anticoagulation therapy (such as warfarin) which cannot be discontinued for 7 days before and 14 days after the procedure Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 14 days before and 14 days after the procedure. Use of aspirin is allowed. Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide) Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications Persistent Anemia, defined as Hgb<10 g/dl Estimated Glomerular Filtration Rate (eGFR) or Modified of Diet in Renal Diseae (MDRD) <30 ml/min/1.73m^2 Active systemic infection Active malignancy within the last 5 years Not potential candidates for surgery or general anesthesia Active illicit substance abuse or alcoholism Participating in another ongoing clinical trial of an investigational drug or device Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation

Ages Eligible for Study
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Minimum Age: 28 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DMR Procedure<br>Subjects randomized to the DMR procedure are unblinded at 24 weeks and followed for an additional 24 weeks. | Procedure: DMR Procedure<br>* The DMR procedure consists of hydrothermal ablation of the duodenum using the Revita System<br>* Other names: Revita;|
| Sham Comparator: Sham Procedure<br>Subjects are unblinded at 24 Weeks. Sham subjects to cross over to receive DMR treatment at 24 Weeks and followed up for additional 24 weeks. | Procedure: Sham Procedure<br>* The sham procedure consists of placing the Revita Catheter into the stomach for 30 minutes and then removing it from the patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at 24 Weeks in Hemoglobin A1c (HbA1c), DMR vs Sham. | The primary efficacy endpoint is the change from baseline at 24 weeks in HbA1c, DMR vs Sham | Baseline and 24 Weeks post-procedure | 
| Change From Baseline at 12 Weeks in MR-PDFF, DMR vs Sham | The absolute change from baseline at 12 weeks in MR-PDFF in patients with baseline MR-PDFF > 5% , DMR vs Sham | Baseline and 12 Weeks post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes, Revita System, DMR