REVITALIZE 1: Evaluation of the Efficacy and Safety of Duodenal Mucosal Resurfacing Using the Revita® System in Subjects With Type 2 Diabetes on Insulin Therapy
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| 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.
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| 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.
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Outcome Measures
Primary Outcome Measures
- The primary endpoint is the percentage of subjects at Week 24 who achieve a HbA1c of </= 7.0% without the need for insulin, DMR vs Sham [24 Weeks]
The primary endpoint will be analyzed using a logistic regression model with terms for baseline insulin dose, baseline HbA1c, change from screening to baseline HbA1c, region (e.g. USA, OUS), baseline FPG, and treatment group.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male, and non-pregnant, non-lactating females
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Age between 21 and 70 years (both inclusive)
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Subjects with T2D on stable dose (up to maximally approved doses) of metformin and up to 2 ADAs (including either GLP1 or DPP-4i and/or, TZD), requiring a minimum of 20 units up to a maximum of 60 units of basal insulin
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Glycosylated hemoglobin A1c (HbA1c) of 7.5-9.5% (both inclusive) confirmed at the end of at least 3 weeks stable run-in period
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FPG ≥180 to <270 mg/dL (measured after overnight 8-hour fasting and 24-36 hours after the last dose of glargine) at the end of at least 3 weeks stable run-in period
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Body Mass Index (BMI) ≥ 24 to ≤ 40 kg/m2
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Women of child-bearing potential (WOCBP) should have negative urine beta human chorionic gonadotropin (hCG) pregnancy test and must agree to use two of the established contraceptive methods throughout the study duration
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Able to sign an informed consent form and comply with study requirements.
Exclusion Criteria:
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Known case of absolute insulin deficiency as indicated by clinical assessment, and a fasting plasma C-peptide of <0.6 ng/ml
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Any drugs or concomitant medications (such as psychoactive drugs such as carbamazepine, phenobarbital, sympathomimetics (ephedrine etc.), corticosteroids, anabolic steroids, and male sex hormones such as testosterone, etc.) that can interfere with glucose metabolism
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Subjects who either are on SGLT2i, meglitinides, sulphonylurea (SUs), short or rapid acting insulin or any other class of ADA other than permitted baseline ADAs at the time of consent or who have a known or documented SGLT2i and/or metformin intolerance prior to the study
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Recurrent or severe urinary tract or genital mycotic infections or history of GU infection within 4 weeks prior to informed consent
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ALT >3 times upper limit normal values unless if associated with underlying NAFLD
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Use of an investigational drug within 1 month or 5 half-lives (whichever is longer) before the screening
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Diagnosed with type 1 diabetes or with a recent history of ketoacidosis
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Ketosis-prone T2D
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History of non-healing diabetic ulcers or amputations
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History of more than 1 severe hypoglycemia episode or unawareness within past 6 months of screening
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In case of two or more glucose alert values of ≤70 mg/dL (3.9 mmol/L) unless a clear correctable precipitating factor can be identified/clinically significant hypoglycemia with self-monitored or laboratory plasma glucose level < 54 mg/dL (3.0 mmol/L / severe hypoglycemic episode requiring third party assistance occurring during run-in period
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Known intestinal autoimmune disease, as evidenced by either a positive anti-glutamic acid decarboxylase (GAD) test, including Celiac disease, or pre-existing symptoms of lupus erythematosus, scleroderma, or other autoimmune connective tissue disorder, which affects the small intestine
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Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid stimulating hormone (TSH) value outside the normal range at screening)
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Known history of thyroid cancer or hyperthyroidism who have undergone treatment within past 12 months or inadequately controlled hyperthyroidism
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An uncontrolled endocrine condition such as multiple endocrine neoplasia etc. (except T2D)
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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, active and uncontrolled Gastroesophageal Reflux Disease (GERD) (grade 3 esophagitis or greater)
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Known history of a 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
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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
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Known history of chronic pancreatitis or a recent history of acute pancreatitis within the past year
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Presence of acute or chronic active hepatitis B or C (except if hepatitis C is cured) or cirrhosis; or hepatic decompensation/acute liver disease during the last 6 months; or alcoholic or autoimmune chronic hepatitis
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Symptomatic gallstones or symptomatic kidney stones, acute cholecystitis
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Clinically active systemic infection
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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), who are on potential immunosuppressants or whose immune status makes the subject a poor candidate for clinical trial participation in the opinion of the Investigator
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History of active malignancy or partial remission from clinically significant malignancy within the past 5 years (except basal or squamous cell skin cancer or carcinoma in situ or those received curative treatment and in complete remission for 5 years or if subject confirmed as cancer free)
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Known active coagulopathy, or current upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, or congenital or acquired intestinal telangiectasia
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Subjects with active helicobacter pylori infection (Subjects may be enrolled if they had history of h pylori infection and were successfully treated)
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Known cases of anemia, thalassemia or conditions that affect red blood cell (RBC) turnover such as recent blood transfusion within 90 days
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Use of anticoagulation therapy (such as warfarin, coumadin, novel oral anticoagulants [NOAC]) or anti-platelet agents (such as thienopyridine) which cannot be discontinued for 5-7 days or 2 drug half-lives before the procedure
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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
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Use of drugs known to affect GI motility (e.g., metoclopramide)
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History of moderate to severe chronic kidney disease (CKD), with estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2 (estimated by Modification of Diet in Renal Disease [MDRD]) or end stage renal failure or on dialysis
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History of myocardial infarction, stroke, or major event requiring hospitalization within the last 3 months prior to screening
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History of new or worsening signs or symptoms of coronary heart disease (CHD) within the last 3 months
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Known case of severe peripheral vascular disease
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Known case of symptomatic heart failure with reduced ejection fraction (NYHA Class II-IV) requiring pharmacologic therapy to control symptoms
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Clinically significant electrocardiogram (ECG) findings such as new clinically significant arrythmia or conduction disturbances that increases risk and requires intervention as determined by the investigator
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Subjects who are at risk for pancreatitis particularly those with a recent fasting triglycerides value of > 600 mg/dL value done within past 3 months
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Actively participating in a weight loss program and is currently not in the maintenance phase
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General contraindications to deep or conscious sedation or general anesthesia or high risk as determined by anesthesiologist (e.g., ASA score 4 or higher) or contraindications to upper GI Endoscopy
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History of any illicit alcohol or substance abuse
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Use of weight loss medication such as Meridia, Xenical, or over the counterweight loss medications or other prescribed medications used specifically for purpose of weight loss
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Use of Dietary supplements or herbal preparations that may have unknown effects on glycemic control, risk of bleeding
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Participating in another ongoing clinical trial of an investigational drug or device
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History of non-adherence to treatment in the previous 6 months, as determined by the investigator based on patient history, HbA1c value and/or drug accountability
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Any other mental or physical condition which, in the opinion of the investigator, makes the subject a poor candidate for clinical trial participation
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Unwilling or unable to perform SMBG, complete the subject glycemia diary, or comply with study visits and other study procedures as required per protocol
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Recovered from severe COVID-19 infection (requiring hospitalization) however still have persistent long COVID-19 symptoms (i.e., they have not recovered for several weeks or months since the start of symptoms that were suggestive of COVID-19, irrespective if they are tested or not).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Arizona | Scottsdale | Arizona | United States | 85295 |
| 2 | University of California San Diego | Coronado | California | United States | 92118 |
| 3 | UCLA Health | Los Angeles | California | United States | 90095 |
| 4 | Stanford University Medical Center | Redwood City | California | United States | 94063 |
| 5 | Mills Peninsula Health Center | San Mateo | California | United States | 94401 |
| 6 | Yale | New Haven | Connecticut | United States | 06519 |
| 7 | University of Miami | Miami | Florida | United States | 33137 |
| 8 | Northwestern Unviersity | Evanston | Illinois | United States | 60208 |
| 9 | Indiana University School of Medicine | Indianapolis | Indiana | United States | 46202 |
| 10 | University of Louisville | Louisville | Kentucky | United States | 40202 |
| 11 | Tulane University | New Orleans | Louisiana | United States | 70112 |
| 12 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 13 | Beth Israel | Boston | Massachusetts | United States | 02215 |
| 14 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 15 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 16 | Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 17 | Robert Wood Johnson Medical School | New Brunswick | New Jersey | United States | 08901 |
| 18 | St. Joseph Medical Center | Paterson | New Jersey | United States | 07501 |
| 19 | NYU Langone Gastroenterology Associates | New York | New York | United States | 10016 |
| 20 | Weill Cornell Medicine | New York | New York | United States | 10021 |
| 21 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 22 | Digestive Disease Medicine of Central New York | Utica | New York | United States | 13502 |
| 23 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 24 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 25 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 26 | Baylor St. Luke's Medical Center | Houston | Texas | United States | 77030 |
| 27 | Virginia Commonwealth University Medical Center | Richmond | Virginia | United States | 23298 |
| 28 | University of Washington | Seattle | Washington | United States | 98104 |
| 29 | West Virginia University | Morgantown | West Virginia | United States | 26506 |
| 30 | Cliniques Universitaires de Bruxelles Hopital Erasme | Bruxelles | Belgium | ||
| 31 | Bichat-Claude Bernard Hospital | Paris | France | 75877 | |
| 32 | University College Dublin | Dublin | Ireland | ||
| 33 | Italy Gemelli | Roma | Italy | ||
| 34 | Universiteit Van Amsterdam Academisch Medisch Centrum | Amsterdam | Netherlands | ||
| 35 | Hospital Universitario Virgen Del Rocio | Sevilla | Spain | ||
| 36 | Inselspital | Bern | Switzerland | ||
| 37 | University Hospital Zurich | Zürich | Switzerland | CH-8091 | |
| 38 | King's College Hospital | London | United Kingdom | ||
| 39 | University College Hospital | London | United Kingdom |
Sponsors and Collaborators
- Fractyl Health, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- C-00044