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

Type 2 Diabetes Clinical Trial

— REVITALIZE 1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04419779
• Other study ID #: C-00044
• Status: Recruiting
• Phase: N/A
• Start date: March 8, 2021
• Est. completion date: January 2026

Study information

• Verified date: May 2024
• Source: Fractyl Health Inc.
• Contact: Lynn Wilson
• Phone: 781-208-2564
• Email: lwilson[@]fractyl.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: January 2026
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

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.
• 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.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires de Bruxelles Hopital Erasme	Bruxelles
France	Bichat-Claude Bernard Hospital	Paris
Ireland	University College Dublin	Dublin
Italy	Italy Gemelli	Roma
Netherlands	Universiteit Van Amsterdam Academisch Medisch Centrum	Amsterdam
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Switzerland	Inselspital	Bern
Switzerland	University Hospital Zurich	Zürich
United Kingdom	Cleveland Clinic London	London	England
United Kingdom	King's College Hospital	London
United States	University of Michigan	Ann Arbor	Michigan
United States	AHN - Avon	Avon	Indiana
United States	Beth Israel	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Investigators Research Group	Brownsburg	Indiana
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Northwestern Unviersity	Evanston	Illinois
United States	Northeast Research Institute, Llc	Fleming Island	Florida
United States	AHN- Franklin	Franklin	Indiana
United States	AHN - Greenfield	Greenfield	Indiana
United States	Baylor St. Luke's Medical Center	Houston	Texas
United States	Biopharma Informatic, Llc	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Jefferson City Medical Group	Jefferson City	Missouri
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Endocrine Associates of West Village	Long Island City	New York
United States	Angel City Research , Inc.	Los Angeles	California
United States	UCLA Health	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Alcanza Clinical Research, LLC	Methuen	Massachusetts
United States	University of Miami	Miami	Florida
United States	West Virginia University	Morgantown	West Virginia
United States	AHN - Muncie	Muncie	Indiana
United States	Yale	New Haven	Connecticut
United States	Tulane University	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Gastroenterology Associates	New York	New York
United States	Synexus Clinical Research, New York	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	Care Access Santa Clarita	Newhall	California
United States	Hoag Hospital	Newport Beach	California
United States	West Orange Endocrinology	Ocoee	Florida
United States	Advent Health Orlando	Orlando	Florida
United States	Synexus Research	Orlando	Florida
United States	St. Joseph Medical Center	Paterson	New Jersey
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Helios CR, Inc	Phoenix	Arizona
United States	Preferred PCP - Pittsburgh	Pittsburgh	Pennsylvania
United States	Preferred Primary Care Physicians	Pittsburgh	Pennsylvania
United States	M3 Wake Research	Raleigh	North Carolina
United States	Stanford University Medical Center	Redwood City	California
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	IMA Clinical Research St. Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	AcellaCare Salisbury	Salisbury	North Carolina
United States	Mills Peninsula Health Center	San Mateo	California
United States	HonorHealth Research Institute	Scottsdale	Arizona
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	AcellaCare Piedmont	Statesville	North Carolina
United States	Simcare Medical Research, Llc.	Sugar Land	Texas
United States	Care Access Warwick	Warwick	Rhode Island
United States	AcellaCare Wilmington	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Fractyl Health Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demonstrate superiority of Revita DMR to sham in improving glycemic control	Change from baseline in HbA1c at Week 24	Baseline to Week 24
Secondary	Demonstrate superiority of Revita DMR to sham in achieving target HbA1c at 24 weeks	The proportion of subjects who achieve an HbA1c of =7.0% at Week 24	Baseline to Week 24
Secondary	Demonstrate superiority of Revita DMR to sham in fasting glucose at 24 weeks	Change from baseline in fasting plasma glucose (FPG) at Week 24	Baseline to Week 24
Secondary	Demonstrate superiority of Revita DMR to sham in weight loss at 24 weeks	Percentage of total body weight loss (%TBWL) from baseline at Week 24	Baseline to Week 24
Secondary	Demonstrate superiority of Revita DMR to sham in insulin requirement at 24 weeks	Percentage change from baseline in insulin total daily dose at Week 24	Baseline to Week 24
Secondary	Demonstrate superiority of Revita DMR to sham in elimination of insulin use at 24 weeks	The proportion of subjects who discontinued insulin at Week 24	Baseline to Week 24