Evaluation of the Efficacy and Safety of DMR Using the Revita® in Subjects With Inadequately Controlled Type 2 Diabetes

NCT ID: NCT04419779

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

NA

Total Enrollment

320 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-08

Study Completion Date

2026-01-31

Brief Summary

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The Revita® system is being investigated to assess the efficacy of DMR versus Sham on improvement in Glycemic, Hepatic and Cardiovascular endpoints for patients with Type 2 Diabetes who are inadequately controlled on one or more glucose lowering agents. The purpose of this study is to demonstrate the efficacy and safety of the Fractyl DMR Procedure using the Revita® System compared to a sham. Subjects randomized to the DMR procedure will be followed per protocol till 48 weeks post treatment. Subjects in the Sham treatment arm will be offered cross over to receive the DMR treatment at 48 weeks and will be followed per protocol for 48 weeks post treatment.

Detailed Description

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Conditions

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Type 2 Diabetes

Keywords

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Type 2 Diabetes Diabetes Mellitus Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Revita System Duodenal Mucosal Resurfacing Insulin-Dependent Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Duodenal Mucosal Resurfacing Sham (Sham)

Duodenal Mucosal Resurfacing Sham (Sham) treatment will include an upper endoscopic procedure similar to DMR treatment without hydrothermal ablation of the duodenal mucosa in patients with inadequately controlled type 2 diabetes.

Group Type SHAM_COMPARATOR

Duodenal Mucosal Resurfacing (Sham)

Intervention Type DEVICE

The Sham procedure consists of placing the Revita® Catheter as described above into the duodenum for a minimum of 30 minutes and then removing it from the patient. Subjects who receive the Sham procedure are followed for 48 weeks post treatment and are offered cross over to undergo the DMR procedure at 48 weeks and are followed for further 48 weeks post treatment. Sham subjects who choose not to cross over are discontinued from the study.

Duodenal Mucosal Resurfacing (DMR)

Duodenal Mucosal Resurfacing (DMR) treatment will include hydrothermal ablation of the duodenal muscosa in an upper endoscopic procedure in patients with inadequately controlled type 2 diabetes.

Group Type ACTIVE_COMPARATOR

Duodenal Mucosal Resurfacing (DMR)

Intervention Type DEVICE

The Fractyl DMR Procedure utilizes the Revita® Catheter to perform hydrothermal ablation of the duodenum. The Catheter is delivered trans-orally over a guide-wire to first inject saline to lift the sub-mucosal space, followed by an ablation of the duodenal mucosa. Subjects who receive the DMR treatment are followed for 48 weeks post treatment.

Interventions

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Duodenal Mucosal Resurfacing (DMR)

The Fractyl DMR Procedure utilizes the Revita® Catheter to perform hydrothermal ablation of the duodenum. The Catheter is delivered trans-orally over a guide-wire to first inject saline to lift the sub-mucosal space, followed by an ablation of the duodenal mucosa. Subjects who receive the DMR treatment are followed for 48 weeks post treatment.

Intervention Type DEVICE

Duodenal Mucosal Resurfacing (Sham)

The Sham procedure consists of placing the Revita® Catheter as described above into the duodenum for a minimum of 30 minutes and then removing it from the patient. Subjects who receive the Sham procedure are followed for 48 weeks post treatment and are offered cross over to undergo the DMR procedure at 48 weeks and are followed for further 48 weeks post treatment. Sham subjects who choose not to cross over are discontinued from the study.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

Subjects must meet all of the following criteria for inclusion in the study:

1. Males and non-pregnant non-lactating females
2. Age between 21 and 70 years (both inclusive)
3. Subjects on at least one glucose lowering agent (GLA) with no changes in GLA medications or dosing for at least 12 weeks prior to the screening visit

Permitted GLAs include:
* Metformin,
* GLP-1 RA including dual peptide agonists and related molecules (e.g., GLP-1/GIP RA),
* DPP-4i,
* TZDs,
* SGLT2is,
* SUs,
* Meglitinides,
* Insulin (basal or basal combined with short-acting), up to a total of 100 units daily
4. HbA1c of 7.5%-10% (both inclusive)
5. BMI \>24 to ≤40 kg/m2
6. WOCBP should have a negative urine beta hCG pregnancy test and must agree to use two of the established contraceptive methods throughout the study duration
7. Able to sign an ICF and comply with study requirements

4. Recurrent or severe urinary tract or genital mycotic infections or history of GU infection within 4 weeks prior to informed consent, for those subjects on SGLT-2
5. ALT or AST \>3 times upper limit of normal (ULN) for the reference range, as determined by the central laboratory at screening visit. Patients with NAFLD are eligible if their ALT level is ≤3.0 times the ULN.
6. Use of an investigational drug within 1 month or 5 half-lives (whichever is longer) before screening
7. Diagnosed with type 1 diabetes or with a recent history of DKA within one year prior to screening
8. Ketosis-prone T2D
9. Known diabetes related non-healing ulcers or amputations (with the exception of a finger or toe amputation occurring \> 1 year prior to screening.
10. History of more than 1 severe hypoglycemia episode or hypoglycemia unawareness within the last 6 months
11. Clinically significant hypoglycemia occurring during the run-in period, defined as a) 2 or more glucose alert values of ≤70 mg/dL (3.9 mmol/L) unless a clear, correctable, precipitating factor can be identified; b) clinically significant hypoglycemia with self-monitored or laboratory plasma glucose level \<54 mg/dL (3.0 mmol/L); or c) severe hypoglycemic episode requiring third party assistance
12. Known intestinal autoimmune disease including celiac disease, ulcerative colitis, Crohn's disease, lupus erythematosus, scleroderma, or other autoimmune connective tissue disorder that affects the small intestine
13. Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid stimulating hormone \[TSH\] value outside the normal range at screening as determined by the central laboratory).
14. Known thyroid cancer or hyperthyroidism with treatment within the past 12 months or inadequately controlled hyperthyroidism (TSH value outside the normal range at screening as determined by the central laboratory).
15. An uncontrolled endocrine condition such as multiple endocrine neoplasia (except T2D)
16. Known structural or functional disorder of the esophagus including any swallowing disorder, esophageal chest pain disorders, drug-refractory esophageal reflux symptoms, or active and uncontrolled gastroesophageal reflux disease (GERD) (defined as Los Angeles Grade C or D esophagitis)
17. Known structural or functional disorder of the stomach including active gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (a large hiatal hernia or type II and higher paraoesophageal hernia), cancer, or any other disorder of the stomach
18. Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Billroth 2, Roux-en-Y gastric bypass, gastric sleeve, or other similar procedures or conditions
19. Known history of chronic pancreatitis or a recent history of acute pancreatitis within the past year
20. Presence of acute or chronic active hepatitis B or C (except if hepatitis C is cured) or cirrhosis, hepatic decompensation/acute liver disease during the last 6 months, or alcoholic or autoimmune chronic hepatitis
21. Symptomatic gallstones, symptomatic kidney stones, or acute cholecystitis
22. Clinically active systemic infection
23. Known immunocompromised status including but not limited to individuals who have undergone organ transplantation, chemotherapy, or radiotherapy within the past 12 months; have clinically significant leukopenia; are positive for the human immunodeficiency virus (HIV); are on potential immunosuppressants; or individuals whose immune status makes the subject a poor candidate for clinical trial participation in the opinion of the investigator
24. Known active malignancy or partial remission from clinically significant malignancy within the past 5 years (except basal or squamous cell skin cancer, carcinoma in situ, those who received curative treatment and are in complete remission for 5 years, or if the subject is confirmed as cancer free)
25. Known active coagulopathy or current upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, or congenital or acquired intestinal telangiectasia
26. Known cases of sickle cell anemia, thalassemia, or conditions that affect red blood cell (RBC) turnover such as a recent blood transfusion within 90 days. Current persistent anemia, defined as hemoglobin \<10g/dL
27. Use of anticoagulation therapy (e.g., warfarin, coumadin, or novel oral anticoagulants \[NOACs\]) or anti-platelet agents (e.g., thienopyridine) which cannot be discontinued for 5-7 days or 2 drug half-lives before the procedure
28. Use of systemic glucocorticoids (excluding topical or ophthalmic applications or inhaled forms) for more than 10 consecutive days within 90 days prior to screening
29. Use of non-GLA drugs known to affect GI motility (e.g., metoclopramide)
30. Known moderate to severe chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) of \<45 mL/min/1.73m2 (estimated by Modification of Diet in Renal Disease \[MDRD\]), end-stage renal failure, or on dialysis
31. History of myocardial infarction, stroke, transient ischemic attack, coronary artery intervention, CHF exacerbation, or any other major cardiac event requiring hospitalization within the last 6 months prior to screening or any cardiac history that would deem subject not eligible for anesthesia (unless documented clearance by cardiologist and/or treating endoscopy team)
32. History of new or worsening signs or symptoms of coronary heart disease (CHD) within the last 3 months
33. Known case of severe peripheral vascular disease, defined as AMA Criteria Class 1 or greater75 (Appendix 19.8)
34. Known case of symptomatic heart failure with reduced ejection fraction (NYHA Class II-IV) requiring pharmacologic therapy to control symptoms
35. Clinically significant electrocardiogram (ECG) findings such as new clinically significant arrhythmia, ST segment changes, or other conduction disturbances that increase risk of heart disease and require intervention as determined by the investigator
36. Subjects who are at risk of pancreatitis, particularly those with a recent fasting triglyceride value of \>600 mg/dL within the past 3 months
37. Actively participating in a weight-loss program and currently not in the maintenance phase
38. General contraindications to deep or conscious sedation, general anesthesia, high risk as determined by anesthesiologist (e.g., ASA score 4 or higher), or contraindications to upper GI endoscopy
39. History of substance use disorder based on the DSM-5 criteria76 within the last 12 months (American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition).
40. Use of weight loss medication such as Meridia, Xenical, over-the-counter weight-loss medications, or other prescribed medications used specifically for the purpose of weight loss
41. Use of dietary supplements or herbal preparations that may have unknown effects on glycemic control or risk of bleeding
42. Participating in another ongoing clinical trial of an investigational drug or device
43. History of non-adherence to treatment in the previous 6 months, as determined by the investigator based on patient history, HbA1c value, or drug accountability
44. Any other mental or physical condition which, in the opinion of the investigator, makes the subject a poor candidate for clinical-trial participation. Physical conditions assessed via endoscopy prior to participant study enrollment at visit 4 include, but not limited to:

1. Active and uncontrolled gastroesophageal reflux disease (GERD) defined as Los Angeles Grade C or D esophagitis
2. Abnormalities of the GI tract preventing endoscopic access to the duodenum
3. Anatomic abnormalities in the duodenum that would preclude the completion of the DMR procedure, including tortuous anatomy
4. Malignancy newly diagnosed by endoscopy

Exclusion Criteria

1. FPG ≥270 mg/dL
2. Known case of absolute insulin deficiency as indicated by clinical assessment or a fasting plasma C-peptide of \<0.6 ng/mL
45. Unwilling or unable to comply with study visits and other study procedures as required per protocol
46. Recovered from severe COVID-19 infection (requiring hospitalization) but with persistent long COVID-19 symptoms (i.e., the individual has not recovered for several weeks or months since the start of symptoms that were suggestive of COVID-19, irrespective if the individual was tested or not)
Minimum Eligible Age

21 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fractyl Health Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Helios CR, Inc

Phoenix, Arizona, United States

Site Status

HonorHealth Research Institute

Scottsdale, Arizona, United States

Site Status

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Site Status

Angel City Research , Inc.

Los Angeles, California, United States

Site Status

UCLA Health

Los Angeles, California, United States

Site Status

Care Access Santa Clarita

Newhall, California, United States

Site Status

Hoag Hospital

Newport Beach, California, United States

Site Status

Stanford University Medical Center

Redwood City, California, United States

Site Status

Mills Peninsula Health Center

San Mateo, California, United States

Site Status

Northeast Research Institute, Llc

Fleming Island, Florida, United States

Site Status

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

West Orange Endocrinology

Ocoee, Florida, United States

Site Status

Advent Health Orlando

Orlando, Florida, United States

Site Status

Synexus Research

Orlando, Florida, United States

Site Status

Northwestern Unviersity

Evanston, Illinois, United States

Site Status

AHN - Avon

Avon, Indiana, United States

Site Status

Investigators Research Group

Brownsburg, Indiana, United States

Site Status

AHN- Franklin

Franklin, Indiana, United States

Site Status

AHN - Greenfield

Greenfield, Indiana, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

AHN - Muncie

Muncie, Indiana, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Tulane University

New Orleans, Louisiana, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Alcanza Clinical Research, LLC

Methuen, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Jefferson City Medical Group

Jefferson City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

IMA Clinical Research St. Louis

St Louis, Missouri, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Endocrine Associates of West Village

Long Island City, New York, United States

Site Status

NYU Langone Gastroenterology Associates

New York, New York, United States

Site Status

Synexus Clinical Research, New York

New York, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

M3 Wake Research

Raleigh, North Carolina, United States

Site Status

AcellaCare Salisbury

Salisbury, North Carolina, United States

Site Status

AcellaCare Piedmont

Statesville, North Carolina, United States

Site Status

AcellaCare Wilmington

Wilmington, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Preferred PCP - Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Preferred Primary Care Physicians

Pittsburgh, Pennsylvania, United States

Site Status

Care Access Warwick

Warwick, Rhode Island, United States

Site Status

Baylor St. Luke's Medical Center

Houston, Texas, United States

Site Status

Biopharma Informatic, Llc

Houston, Texas, United States

Site Status

Simcare Medical Research, Llc.

Sugar Land, Texas, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

Cliniques Universitaires de Bruxelles Hopital Erasme

Brussels, , Belgium

Site Status

University College Dublin

Dublin, , Ireland

Site Status

Italy Gemelli

Roma, , Italy

Site Status

Universiteit Van Amsterdam Academisch Medisch Centrum

Amsterdam, , Netherlands

Site Status

University Hospital Zurich

Zurich, , Switzerland

Site Status

Cleveland Clinic London

London, England, United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Countries

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France Germany Spain United States Belgium Ireland Italy Netherlands Switzerland United Kingdom

Other Identifiers

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C-00044

Identifier Type: -

Identifier Source: org_study_id