Evaluation of the Efficacy and Safety of Duodenal Mucosal Resurfacing Using the Revita® System in Subjects With Type 2 Diabetes on Insulin Therapy (REVITALIZE 1)

April 19, 2024 updated by: Fractyl Health Inc.

A Prospective, Randomized, Double-Blind, Sham-Controlled, Multi-Center Pivotal Study to Evaluate the Efficacy and Safety of Duodenal Mucosal Resurfacing Using the Revita® System in Subjects With Type 2 Diabetes on Insulin Therapy

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 with insulin therapy. 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

320

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Bruxelles, Belgium
        • Recruiting
        • Cliniques Universitaires de Bruxelles Hopital Erasme
        • Contact:
        • Principal Investigator:
          • Miriam Cnop
  • France
      • Paris, France, 75877
        • Withdrawn
        • Bichat-Claude Bernard Hospital
  • Ireland
      • Dublin, Ireland
        • Not yet recruiting
        • University College Dublin
        • Principal Investigator:
          • Carel le Roux
        • Contact:
  • Italy
  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • Universiteit Van Amsterdam Academisch Medisch Centrum
        • Principal Investigator:
          • Jacques Bergman
        • Contact:
  • Spain
      • Sevilla, Spain
        • Withdrawn
        • Hospital Universitario Virgen del Rocío
  • Switzerland
      • Bern, Switzerland
        • Withdrawn
        • Inselspital
      • Zürich, Switzerland, CH-8091
        • Active, not recruiting
        • University Hospital Zurich
  • United Kingdom
      • London, United Kingdom
        • Active, not recruiting
        • King's College Hospital
    • England
      • London, England, United Kingdom, SW1X &AW
        • Recruiting
        • Cleveland Clinic London
        • Contact:
          • Margaret Duku
          • Phone Number: +44 20 3423 7500
          • Email: DUKUM@ccf.org
        • Principal Investigator:
          • Rehan Haidry
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85028
        • Active, not recruiting
        • Helios CR, Inc
      • Scottsdale, Arizona, United States, 85295
        • Recruiting
        • Mayo Clinic Arizona
        • Principal Investigator:
          • Rahul Pannala
        • Contact:
        • Sub-Investigator:
          • Lori Roust
      • Scottsdale, Arizona, United States, 85258
        • Active, not recruiting
        • HonorHealth Research Institute
    • California
      • Los Angeles, California, United States, 90095
      • Los Angeles, California, United States, 90010
        • Recruiting
        • Angel City Research , Inc.
        • Contact:
        • Principal Investigator:
          • Felix Sigal
      • Newhall, California, United States, 91321
        • Recruiting
        • Care Access Santa Clarita
        • Principal Investigator:
          • Sina Tebi
        • Contact:
      • Redwood City, California, United States, 94063
        • Recruiting
        • Stanford University Medical Center
        • Principal Investigator:
          • Paul Kwo
        • Contact:
      • San Mateo, California, United States, 94401
        • Recruiting
        • Mills Peninsula Health Center
        • Principal Investigator:
          • David Klonoff
        • Contact:
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Withdrawn
        • Yale
    • Florida
      • Fleming Island, Florida, United States, 32003
        • Active, not recruiting
        • Northeast Research Institute, Llc
      • Jacksonville, Florida, United States, 32216
        • Active, not recruiting
        • Jacksonville Center for Clinical Research
      • Miami, Florida, United States, 33137
        • Recruiting
        • University of Miami
        • Principal Investigator:
          • Paul Martin
        • Contact:
      • Ocoee, Florida, United States, 34761
        • Recruiting
        • West Orange Endocrinology
        • Contact:
        • Principal Investigator:
          • Jose Mandry
      • Orlando, Florida, United States, 32804
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Synexus Research
        • Contact:
        • Principal Investigator:
          • Akbar Safder
    • Illinois
      • Evanston, Illinois, United States, 60208
        • Recruiting
        • Northwestern Unviersity
        • Principal Investigator:
          • Grazia Aleppo
        • Contact:
    • Indiana
      • Avon, Indiana, United States, 46123
      • Brownsburg, Indiana, United States, 46112
        • Recruiting
        • Investigators Research Group
        • Contact:
        • Principal Investigator:
          • Kenneth Maynard
      • Franklin, Indiana, United States, 46131
        • Recruiting
        • AHN- Franklin
        • Contact:
        • Principal Investigator:
          • Mitch Cornett
      • Greenfield, Indiana, United States, 46140
        • Active, not recruiting
        • AHN - Greenfield
      • Indianapolis, Indiana, United States, 46202
        • Active, not recruiting
        • Indiana University School of Medicine
      • Muncie, Indiana, United States, 47304
        • Recruiting
        • AHN - Muncie
        • Principal Investigator:
          • Jonathan David Condit
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Not yet recruiting
        • University of Louisville
        • Principal Investigator:
          • Prakash Mokshagundam
        • Contact:
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Active, not recruiting
        • Tulane University
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Principal Investigator:
          • Vanita Aroda
        • Contact:
      • Boston, Massachusetts, United States, 02215
        • Withdrawn
        • Beth Israel
      • Methuen, Massachusetts, United States, 01844
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Principal Investigator:
          • Elif Oral
        • Contact:
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Julie Silverstein
        • Contact:
      • Saint Louis, Missouri, United States, 63117
        • Active, not recruiting
        • IMA Clinical Research St. Louis
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
    • New Jersey
      • Paterson, New Jersey, United States, 07501
        • Withdrawn
        • St. Joseph Medical Center
    • New York
      • Long Island City, New York, United States, 77089
        • Recruiting
        • Endocrine Associates of West Village
        • Principal Investigator:
          • Anastasios Manessis
        • Contact:
      • New York, New York, United States, 10065
        • Recruiting
        • Weill Cornell Medicine
        • Principal Investigator:
          • Reem Sharaiha
        • Contact:
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Principal Investigator:
          • Reshmi Srinath
        • Contact:
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Gastroenterology Associates
        • Principal Investigator:
          • Akankasha Goyal
        • Contact:
      • New York, New York, United States, 10017
        • Recruiting
        • Synexus Clinical Research, New York
        • Contact:
        • Principal Investigator:
          • Margarita Nunez
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Principal Investigator:
          • Jennifer Rowell
        • Contact:
      • Salisbury, North Carolina, United States, 28144
        • Active, not recruiting
        • AcellaCare Salisbury
      • Statesville, North Carolina, United States, 28625
      • Wilmington, North Carolina, United States, 28401
        • Active, not recruiting
        • AcellaCare Wilmington
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Principal Investigator:
          • John Vargo
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Pittsburgh, Pennsylvania, United States, 15201
        • Recruiting
        • Preferred PCP - Pittsburgh
        • Contact:
        • Principal Investigator:
          • Daniel Austin
      • Pittsburgh, Pennsylvania, United States, 15236
        • Active, not recruiting
        • Preferred Primary Care Physicians
    • Rhode Island
      • Warwick, Rhode Island, United States, 02886-4463
        • Recruiting
        • Care Access Warwick
        • Principal Investigator:
          • Sudhir Bansal
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor St. Luke's Medical Center
        • Contact:
        • Principal Investigator:
          • Mohamed Othman, MD
      • Houston, Texas, United States, 77089
        • Recruiting
        • Biopharma Informatic, Llc
        • Contact:
        • Principal Investigator:
          • Amir Hassan
      • Sugar Land, Texas, United States, 77478
        • Recruiting
        • Simcare Medical Research, Llc.
        • Contact:
        • Principal Investigator:
          • Imran Siddiqui
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Withdrawn
        • Virginia Commonwealth University Medical Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • University of Washington Seattle
        • Principal Investigator:
          • Arthi Thiramulai
        • Contact:
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Recruiting
        • West Virginia University
        • Principal Investigator:
          • Adnan Haider
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male, and non-pregnant, non-lactating females
  2. Age between 21 and 70 years (both inclusive)

  3. Subjects with type 2 diabetes on stable doses of 20-100 units (both inclusive) of total daily insulin dose of basal insulin or basal insulin combined with short-acting insulin and up to 3 permitted non-insulin antidiabetic agents (ADAs). Permitted non-insulin ADAs include:

    • Metformin,
    • Glucagon-like peptide-1 receptor agonist (GLP-1 RA) including dual peptide agonists and related molecules (e.g., glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA),
    • Dipeptidyl peptidase 4 inhibitor (DPP-4i),
    • Thiazolidinediones (TZD),
    • Sodium-glucose cotransporter 2 inhibitors (SGLT2i),
    • Sulfonylureas (SU),
    • Meglitinides
  4. Glycosylated hemoglobin A1c (HbA1c) of 7.5-10% (both inclusive)
  5. Body mass index (BMI) > 24 to ≤ 40 kg/m^2
  6. Women of childbearing potential (WOCBP) should have a negative urine beta human chorionic gonadotrophin (hCG) pregnancy test and must agree to use two established contraceptive methods throughout the study duration.
  7. Able to sign an informed consent form and comply with study requirements

Exclusion Criteria:

  1. FPG >270 mg/dL
  2. Known case of absolute insulin deficiency as indicated by clinical assessment a fasting plasma C-peptide of <0.6 ng/ml
  3. Subjects on any other class of glucose-lowering agents other than GLAs listed in inclusion criteria
  4. Any drugs or concomitant medications (e.g., psychoactive drugs such as carbamazepine, phenobarbital, sympathomimetics such as ephedrine, corticosteroids, anabolic steroids, and male sex hormones such as testosterone) that can interfere with glucose metabolism
  5. Recurrent or severe urinary tract or genital mycotic infections or history of genitourinary infection within 4 weeks prior to informed consent
  6. ALT or AST >3 times upper limit normal values
  7. Use of an investigational drug within 1 month or 5 half-lives (whichever is longer) before the screening
  8. Diagnosed with type 1 diabetes or with a recent history of ketoacidosis
  9. Ketosis-prone T2D
  10. Known diabetes related non-healing diabetic ulcers or amputations
  11. History of more than 1 severe hypoglycemia episode or hypoglycemia unawareness within past 6 months
  12. 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); c) severe hypoglycemic episode requiring third party assistance
  13. Known intestinal autoimmune disease, including celiac disease, ulcerative colitis, Crohn's disease, lupus erythematosus, scleroderma, or other autoimmune connective tissue disorder, which affects the small intestine
  14. Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid stimulating hormone [TSH] value outside the normal range at screening)
  15. Known history of thyroid cancer or hyperthyroidism with treatment within the past 12 months or inadequately controlled hyperthyroidism
  16. An uncontrolled endocrine condition such as multiple endocrine neoplasia (except T2D)
  17. Known history of a 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) (grade 3 esophagitis or greater)
  18. Known structural or functional disorder of the stomach including 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
  19. 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
  20. Known history of chronic pancreatitis or a recent history of acute pancreatitis within the past year
  21. 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
  22. Symptomatic gallstones, symptomatic kidney stones, or acute cholecystitis
  23. Clinically active systemic infection
  24. 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
  25. 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)
  26. Known active coagulopathy or current upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, or congenital or acquired intestinal telangiectasia
  27. Known cases of anemia, thalassemia, or conditions that affect red blood cell (RBC) turnover such as a recent blood transfusion within 90 days
  28. Use of anticoagulation therapy (e.g., warfarin, coumadin, or novel oral anticoagulants such as NOAC) or anti-platelet agents (e.g., thienopyridine) which cannot be discontinued for 5-7 days or 2 drug half-lives before the procedure
  29. Use of systemic glucocorticoids (excluding topical or ophthalmic applications or inhaled forms) for more than 10 consecutive days within 90 days prior to the screening visit
  30. Use of non-GLA drugs known to affect GI motility (e.g., metoclopramide)
  31. 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
  32. History of myocardial infarction, stroke, transient ischemic attack, coronary artery intervention, CHF exacerbation, or a major event requiring hospitalization within the last 6 months prior to screening
  33. History of new or worsening signs or symptoms of coronary heart disease (CHD) within the last 3 months
  34. Known case of severe peripheral vascular disease, disease, defined as AMA Criteria Class 1 or greater
  35. Known case of symptomatic heart failure with reduced ejection fraction (NYHA Class II-IV) requiring pharmacologic therapy to control symptoms
  36. 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
  37. Subjects who are at risk of pancreatitis, particularly those with a recent fasting triglyceride value of >600 mg/dL within the past 3 months
  38. Actively participating in a weight-loss program and currently not in the maintenance phase
  39. 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
  40. History of substance use disorder based on the DSM-5 criteria within the last 12 months.
  41. 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
  42. Use of dietary supplements or herbal preparations that may have unknown effects on glycemic control or risk of bleeding
  43. Participating in another ongoing clinical trial of an investigational drug or device
  44. 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
  45. Any other mental or physical condition which, in the opinion of the investigator, makes the subject a poor candidate for clinical-trial participation
  46. Unwilling or unable to perform SMBG, complete the subject glycemia diary, or comply with study visits and other study procedures as required per protocol
  47. 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 is tested or not)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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 type 2 diabetes on insulin.
Device: 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.
Sham Comparator: 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 type 2 diabetes on insulin.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Demonstrate superiority of Revita DMR to sham in improving glycemic control
Time Frame: Baseline to Week 24
Change from baseline in HbA1c at Week 24
Baseline to Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Demonstrate superiority of Revita DMR to sham in achieving target HbA1c at 24 weeks
Time Frame: Baseline to Week 24
The proportion of subjects who achieve an HbA1c of ≤7.0% at Week 24
Baseline to Week 24
Demonstrate superiority of Revita DMR to sham in fasting glucose at 24 weeks
Time Frame: Baseline to Week 24
Change from baseline in fasting plasma glucose (FPG) at Week 24
Baseline to Week 24
Demonstrate superiority of Revita DMR to sham in weight loss at 24 weeks
Time Frame: Baseline to Week 24
Percentage of total body weight loss (%TBWL) from baseline at Week 24
Baseline to Week 24
Demonstrate superiority of Revita DMR to sham in insulin requirement at 24 weeks
Time Frame: Baseline to Week 24
Percentage change from baseline in insulin total daily dose at Week 24
Baseline to Week 24
Demonstrate superiority of Revita DMR to sham in elimination of insulin use at 24 weeks
Time Frame: Baseline to Week 24
The proportion of subjects who discontinued insulin at Week 24
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fractyl Health Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 8, 2021

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

June 3, 2020

First Submitted That Met QC Criteria

June 3, 2020

First Posted (Actual)

June 5, 2020

Study Record Updates

Last Update Posted (Actual)

April 22, 2024

Last Update Submitted That Met QC Criteria

April 19, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C-00044

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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