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Safety & Effectiveness of Duodenal Mucosal Resurfacing (DMR) Using the Revita™ System in Treatment of Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT03653091
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Fractyl Laboratories, Inc.

Brief Summary:
The Revita™ System is being investigated to assess the ability to improve glycemic control in conjunction with diet and exercise in patients with Type 2 diabetes who are inadequately controlled with oral anti-diabetic medications. The purpose of this study is to demonstrate the safety and effectiveness of the Fractyl DMR Procedure using the Revita™ System compared to a sham procedure. At 24 weeks, subjects randomized to the DMR procedure be continued to be followed per protocol till 48 Weeks and the Sham treatment arm will be offered to cross over to receive the DMR treatment and will be followed per protocol for 24 weeks post treatment.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Device: Duodenal Mucosal Resurfacing (DMR) Device: Duodenal Mucosal Resurfacing Sham (Sham) Not Applicable

Detailed Description:
The study is a randomized, double-blind sham-controlled prospective multi-center clinical investigation of subjects with T2D sub-optimally controlled on two oral anti-diabetic medications, one of which must be metformin, comparing the Fractyl DMR procedure using the Revita™ System to a sham procedure. All subjects will participate in a 4 week oral anti-diabetic medication run-in period before the procedure to confirm inadequate blood glucose control in conjunction with medication compliance and nutritional counseling. Subjects who meet all criteria after screening are randomized 2:1 (DMR to sham), with double blinding (subject and endocrinologist/Sponsor). The endoscopist is not blinded.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Sham-Controlled, Prospective, Multi-Center Pilot Study to Evaluate the Safety and Effectiveness of Duodenal Mucosal Resurfacing Using the Revita™ System in the Treatment of Type 2 Diabetes
Actual Study Start Date : September 28, 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : February 2020

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 mucosa in an upper endoscopic procedure in patients with type 2 diabetes.
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 DRM treatment are followed for 48 weeks while Sham subjects who cross over and undergo the DMR procedure at 24 weeks are followed for further 24 weeks post treatment. Sham subjects who choose not to cross over are discontinued from the study.

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.
Device: Duodenal Mucosal Resurfacing Sham (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.




Primary Outcome Measures :
  1. Device or procedure related SAEs or UADEs [ Time Frame: 24 weeks post procedure ]
    Number subjects with reported device or procedure related SAEs or UADEs


Secondary Outcome Measures :
  1. Change in hemoglobin A1c (HbA1c) [ Time Frame: 24 weeks post procedure ]
    Change in HbA1c from baseline in DMR vs Sham groups

  2. HbA1c change by visit over time [ Time Frame: 24 weeks post procedure ]
    HbA1c change from baseline to Week 24 by visit over time, DMR vs. Sham

  3. Fasting Plasma Glucose (FPG) change [ Time Frame: 24 weeks post procedure ]
    FPG change from baseline to Week 24, DMR vs. Sham

  4. FPG change by visit over time [ Time Frame: 24 weeks post procedure ]
    FPG change from baseline to Week 24 by visit over time, DMR vs. Sham

  5. Proportion of DMR-treated subjects with an HbA1c improvement [ Time Frame: 48 weeks post procedure ]
    Proportion of DMR-treated subjects with an HbA1c improvement from baseline at 24 weeks that maintain an HbA1c improvement at 48 weeks

  6. Urine Albumin Creatinine Ratio (UACR) change [ Time Frame: 24 weeks post procedure ]
    UACR change from baseline to Week 24, DMR vs. Sham

  7. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) change [ Time Frame: 24 weeks post procedure ]
    Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) change from baseline to Week 24, DMR vs. Sham



Information from the National Library of Medicine

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Ages Eligible for Study:   28 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and non-pregnant women 28-65 years of age
  2. Diagnosed with T2D for at least 3 years
  3. A1C of 7.5 - 9.5% (59-80 mmol/mol)
  4. BMI ≥ 28 and ≤ 40 kg/m2
  5. On two to three oral OADs (metformin plus one to two additional OADs) with two (see note below) at least at half maximum labeled dose (or highest tolerated) with no changes in medication in the 12 weeks prior to the Screening Visit (Visit 1) (Refer to ADA Standard of Medical Care in Diabetes 2018, Table 8.3 for the maximum approved daily dose of non-insulin glucose lowering agents) (43). Note: For subjects on sulfonylurea (SU) glucose-lowering drugs for diabetes, the only SUs permitted in the study will be glipizide or glimepiride, and their doses below half maximum labeled dosing will not be an exclusion for study entry. Patients unwilling to reduce the dose of SU at the time of the DMR procedure as described by protocol will be excluded.
  6. Agree to use an additional glucose-lowering treatment (eg, liraglutide, other OAD with the exception of glyburide) if recommended by the study investigator in case of persistent hyperglycemia.
  7. Agree not to donate blood during their participation in the study
  8. Able to comply with study requirements and understand and sign the Informed Consent Form
  9. Women of childbearing potential (WOCBP) must be using two acceptable methods of contraception throughout the study
  10. Women must not be breastfeeding

Exclusion Criteria:

  1. Diagnosed with Type 1 Diabetes (T1D)
  2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma
  3. Probable insulin production failure, defined as fasting C Peptide serum <1 ng/mL (333pmol/l)
  4. Previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes)
  5. Current use of injectable medications for diabetes (insulin, GLP-1RA)
  6. Current use of glyburide, a sulfonylurea (SU) glucose-lowering drug for diabetes
  7. Hypoglycemia unawareness or a history of severe hypoglycemia (more than 1 severe hypoglycemic event, as defined by need for third-party-assistance, in the last year)
  8. Known autoimmune disease, including but not limited to celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder
  9. Previous GI surgery that could limit treatment of the duodenum such as Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions
  10. History of chronic or acute pancreatitis
  11. History of diabetic gastroparesis
  12. Known active hepatitis or active liver disease
  13. Acute gastrointestinal illness in the previous 7 days
  14. Known history irritable bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease
  15. Known history of a structural or functional disorder of the esophagus that may impede passage of the device through the gastrointestinal tract or increase risk of esophageal damage during an endoscopic procedure, including Barrett's esophagus, esophagitis, dysphagia, achalasia, stricture/stenosis, esophageal varices, esophageal diverticula, esophageal perforation, or any other disorder of the esophagus
  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
  17. Known history of a structural or functional disorder of the stomach including gastroparesis, gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (> 2 cm), cancer or any other disorder of the stomach
  18. Known history of chronic symptoms suggestive of a structural or functional disorder of the stomach, including any symptoms of chronic upper abdominal pain, chronic nausea, chronic vomiting, chronic dyspepsia or symptoms suggestive of gastroparesis, including post-prandial fullness or pain, post-prandial nausea or vomiting or early satiety
  19. Known history of duodenal ulcer, intestinal diverticula (diverticulitis), intestinal varices, intestinal stricture/stenosis, small bowel obstruction, or any other obstructive disorder of the GI tract
  20. Currently have ongoing symptoms suggestive of intermittent small bowel obstruction, such as recurrent bouts of post-prandial abdominal pain, nausea or vomiting
  21. Active H. pylori infection (Subjects with active H. pylori may continue with the screening process if they are treated with an appropriate antibiotic regimen)
  22. History of coagulopathy, upper gastrointestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia
  23. Current use of anticoagulation therapy (such as warfarin) which cannot be discontinued for 7 days before and 14 days after the procedure
  24. Current use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 14 days before and 14 days after the procedure.
  25. Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during treatment through 4 weeks following the procedure. Use of low dose aspirin is allowed.
  26. Current use of serotonergic medications (SSRI)
  27. 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
  28. Use of drugs known to affect GI motility (e.g. Metoclopramide)
  29. Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications
  30. Untreated/inadequately treated hypothyroidism, defined as an elevated Thyroid-Stimulating Hormone (TSH) level at Screening; if on thyroid hormone replacement therapy, must be on stable dose for at least 6 weeks prior to Screening
  31. Persistent Anemia, defined as Hemoglobin <10 g/dL
  32. Subjects who have donated blood or received a transfusion in the prior 3 months
  33. Subjects with conditions that alter red blood cell turnover
  34. Subjects with prosthetic joints
  35. Significant cardiovascular disease including known history of valvular disease, or myocardial infarction, heart failure, transient ischemic attack or stroke within the last 6 months
  36. Moderate or severe chronic kidney disease (CKD), with estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2 (estimated by MDRD)
  37. 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) or whose immune status makes the subject a poor candidate for clinical trial participation in the opinion of the Investigator
  38. Active systemic infection
  39. Active malignancy within the last 5 years (with the exception of treated basal cell or treated squamous cell carcinoma)
  40. Subjects with a personal or family history of medullary thyroid carcinoma
  41. Subjects with Multiple Endocrine Neoplasia syndrome type 2
  42. Not a candidate for surgery or general anesthesia
  43. Active illicit substance abuse or alcoholism
  44. Current smoker
  45. Participating in another ongoing clinical trial of an investigational drug or device
  46. Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation
  47. Unwilling or unable to perform SMBG, complete the patient diary, or comply with study visits and other study procedures as required per protocol

Additional exclusion criteria to be confirmed during the screening process:

  1. A1c post Run-In Phase < 7.5% (59 mmol/mol) or > 9.5% (86 mmol/mol)
  2. Any severe hypoglycemic event, defined as hypoglycemia requiring third-party assistance; or any clinically significant hypoglycemic event, defined as self-monitored or laboratory plasma glucose level < 54 mg/dL (3.0 mmol/L); or ≥ 2 glucose alert values ≤70 mg/dL (3.9 mmol/L), unless a clear correctable precipitating factor can be identified, since the screening visit (Visit 1)
  3. Uncontrolled hyperglycemia with a glucose level >270 mg/dl (>15 mmol/L) after an overnight fast or >360 mg/dl (>20 mmol/l) in a randomly performed measurement during Medication Run-In Period and confirmed by a second measurement (not on the same day)
  4. Mean of 3 separate blood pressure measurements >180 mmHg (systolic) or >100 mmHg (diastolic)
  5. WOCBP with a positive urine pregnancy test at Baseline Visit
  6. Active and uncontrolled GERD defined as grade III esophagitis or greater
  7. Abnormalities of the GI tract preventing endoscopic access to the duodenum
  8. Anatomic abnormalities in the duodenum that would preclude the completion of the DMR procedure, including tortuous anatomy
  9. Malignancy newly diagnosed by endoscopy
  10. Upper gastrointestinal conditions such as ulcers, polyps, varices, strictures, congenital or acquired intestinal telangiectasia

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): NCT03653091


Contacts
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Contact: Olga Ohayon +17816919275 olga@fractyl.com
Contact: Karen Hager +17819028840 Khager@fractyl.com

Locations
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United States, Florida
Florida Hospital / TRANSLATIONAL RESEARCH INSTITUTE FOR METABOLISM AND DIABETES (TRI) Recruiting
Orlando, Florida, United States, 32804
Contact: Quianna Stokes-Washington    407-303-7100    TRI@flhosp.org   
Principal Investigator: Steven Smith, MD         
Sub-Investigator: Robert Hawes, MD         
United States, New Hampshire
Dartmouth Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Jessica Chevalier    603-653-9033    Jessica.I.Chevalier@hitchcock.org   
Contact: Penny Doughty    603.650.8360    Penny.J.Doughty@hitchcock.org   
Principal Investigator: Susheela Chaidarun, MD         
Sub-Investigator: Richard Rothstein, MD         
United States, Pennsylvania
University of Pennsylvania - Penn Metabolic Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Anastassia Amaro, MD    215-294-9525    Anastassia.Amaro@uphs.upenn.edu   
Contact: Gregory G. Ginsberg, MD    215-349-8222    Gregory.Ginsberg@uphs.upenn.edu   
Principal Investigator: Anastassia Amaro, MD         
Sub-Investigator: Gregory G. Ginsberg, MD         
United States, Texas
UTHealth Recruiting
Houston, Texas, United States, 77030
Contact: Prithvi Patil, MS    713-500-6456    Prithvi.B.Patil@uth.tmc.edu   
Contact: Ilimbek Beketaev    713-500-5232    ilimbek.beketaev@uth.tmc.edu   
Principal Investigator: Absalon Gutierrez, MD         
Sub-Investigator: Nirav Thosani, MD         
Texas Diabetes Institute Recruiting
San Antonio, Texas, United States, 78229
Contact: Khanh Horst, RN, CRC    210-358-7210    Horst@uthscsa.edu   
Contact: Andrea Hansis-Diarte    210-567-3208    HansisDiarte@uthscsa.edu   
Principal Investigator: Ralph DeFronzo, MD         
Sub-Investigator: Sandeep Patel, MD         
Sponsors and Collaborators
Fractyl Laboratories, Inc.

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Responsible Party: Fractyl Laboratories, Inc.
ClinicalTrials.gov Identifier: NCT03653091     History of Changes
Other Study ID Numbers: C-40000
First Posted: August 31, 2018    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019

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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
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Fractyl Laboratories, Inc.:
Type 2 diabetes
Diabetes Mellitus
Noninsulin-Dependent Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Revita System
Anti-diabetic medications
Duodenal Mucosal Resurfacing

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases