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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04419779
Recruitment Status : Recruiting
First Posted : June 5, 2020
Last Update Posted : May 11, 2022
Sponsor:
Information provided by (Responsible Party):
Fractyl Laboratories, Inc. ( Fractyl Health, Inc. )

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
Type 2 Diabetes Device: Duodenal Mucosal Resurfacing (DMR) Device: Duodenal Mucosal Resurfacing (Sham) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 560 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 8, 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine


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-musical 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.




Primary Outcome Measures :
  1. 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 [ Time Frame: 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.



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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male, and non-pregnant, non-lactating females
  2. Age between 21 and 70 years (both inclusive)
  3. 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
  4. Glycosylated hemoglobin A1c (HbA1c) of 7.5-9.5% (both inclusive) confirmed at the end of at least 3 weeks stable run-in period
  5. 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
  6. Body Mass Index (BMI) ≥ 24 to ≤ 40 kg/m2
  7. 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
  8. Able to sign an informed consent form and comply with study requirements.

Exclusion Criteria:

  1. Known case of absolute insulin deficiency as indicated by clinical assessment, and a fasting plasma C-peptide of <0.6 ng/ml
  2. 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
  3. 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
  4. Recurrent or severe urinary tract or genital mycotic infections or history of GU infection within 4 weeks prior to informed consent
  5. ALT >3 times upper limit normal values unless if associated with underlying NAFLD
  6. Use of an investigational drug within 1 month or 5 half-lives (whichever is longer) before the screening
  7. Diagnosed with type 1 diabetes or with a recent history of ketoacidosis
  8. Ketosis-prone T2D
  9. History of non-healing diabetic ulcers or amputations
  10. History of more than 1 severe hypoglycemia episode or unawareness within past 6 months of screening
  11. 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
  12. 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
  13. Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid stimulating hormone (TSH) value outside the normal range at screening)
  14. Known history of thyroid cancer or hyperthyroidism who have undergone treatment within past 12 months or inadequately controlled hyperthyroidism
  15. An uncontrolled endocrine condition such as multiple endocrine neoplasia etc. (except T2D)
  16. 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)
  17. 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
  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; or hepatic decompensation/acute liver disease during the last 6 months; or alcoholic or autoimmune chronic hepatitis
  21. Symptomatic gallstones or symptomatic kidney stones, 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, 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
  24. 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)
  25. Known active coagulopathy, or current upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, or congenital or acquired intestinal telangiectasia
  26. Subjects with active helicobacter pylori infection (Subjects may be enrolled if they had history of h pylori infection and were successfully treated)
  27. Known cases of anemia, thalassemia or conditions that affect red blood cell (RBC) turnover such as recent blood transfusion within 90 days
  28. 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
  29. 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
  30. Use of drugs known to affect GI motility (e.g., metoclopramide)
  31. 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
  32. History of myocardial infarction, stroke, or major event requiring hospitalization within the last 3 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
  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 arrythmia or conduction disturbances that increases risk and requires intervention as determined by the investigator
  37. 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
  38. Actively participating in a weight loss program and is currently not in the maintenance phase
  39. 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
  40. History of any illicit alcohol or substance abuse
  41. 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
  42. Use of Dietary supplements or herbal preparations that may have unknown effects on glycemic control, 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 and/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) 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04419779


Contacts
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Contact: Sarah Hackett 781-902-8840 shackett@fractyl.com
Contact: Christine Delano 781-516-7056 cdelano@fractyl.com

Locations
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Sponsors and Collaborators
Fractyl Health, Inc.
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Responsible Party: Fractyl Health, Inc.
ClinicalTrials.gov Identifier: NCT04419779    
Other Study ID Numbers: C-00044
First Posted: June 5, 2020    Key Record Dates
Last Update Posted: May 11, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Fractyl Laboratories, Inc. ( Fractyl Health, Inc. ):
Type 2 Diabetes
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Revita System
Duodenal Mucosal Resurfacing
Insulin-Dependent Diabetes Mellitus
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases