ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    C-40000
Previous Study | Return to List | Next Study

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

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: NCT03653091
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : October 25, 2018
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.

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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. Fasting Plasma Insulin > 7.0 µU/mL
  4. HbA1C of 7.5 - 9.5% (59-80 mmol/mol)
  5. BMI ≥ 28 and ≤ 40 kg/m2
  6. On two oral OADs (metformin plus one additional OAD) 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)
  7. Agree to use an additional glucose-lowering treatment (eg, liraglutide or other non-SU OAD) if recommended by the study investigator in case of persistent hyperglycemia.
  8. Agree not to donate blood during their participation in the study
  9. Able to comply with study requirements and understand and sign the Informed Consent Form
  10. Women of childbearing potential (WOCBP) must be using two acceptable methods of contraception throughout the study
  11. Women must not be breastfeeding

Exclusion Criteria:

  1. Diagnosed with Type 1 Diabetes (T1D)
  2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma
  3. Previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes)
  4. Current use of injectable medications for diabetes (insulin, GLP-1RA)
  5. Current use of a sulfonylurea (SU) glucose-lowering drug for diabetes
  6. 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)
  7. 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
  8. 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
  9. History of chronic or acute pancreatitis
  10. History of diabetic gastroparesis
  11. Known active hepatitis or active liver disease
  12. Acute gastrointestinal illness in the previous 7 days
  13. Known history irritable bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. Currently have ongoing symptoms suggestive of intermittent small bowel obstruction, such as recurrent bouts of post-prandial abdominal pain, nausea or vomiting
  20. Active H. pylori infection (Subjects with active H. pylori may continue with the screening process if they are treated with an appropriate antibiotic regimen)
  21. History of coagulopathy, upper gastrointestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia
  22. Current use of anticoagulation therapy (such as warfarin) which cannot be discontinued for 7 days before and 14 days after the procedure
  23. Current use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 14 days before and 14 days after the procedure. Use of aspirin is allowed.
  24. Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during treatment through 4 weeks following the procedure
  25. Current use of serotonergic medications (SSRI)
  26. 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
  27. Use of drugs known to affect GI motility (e.g. Metoclopramide)
  28. Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications
  29. 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
  30. Persistent Anemia, defined as Hemoglobin <10 g/dL
  31. Subjects who have donated blood or received a transfusion in the prior 3 months
  32. Subjects with conditions that alter red blood cell turnover
  33. Subjects with prosthetic joints
  34. Significant cardiovascular disease including known history of valvular disease, or myocardial infarction, heart failure, transient ischemic attack or stroke within the last 6 months
  35. Moderate or severe chronic kidney disease (CKD), with estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2 (estimated by MDRD)
  36. 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
  37. Active systemic infection
  38. Active malignancy within the last 5 years (with the exception of treated basal cell or treated squamous cell carcinoma)
  39. Subjects with a personal or family history of medullary thyroid carcinoma
  40. Subjects with Multiple Endocrine Neoplasia syndrome type 2
  41. Not a candidate for surgery or general anesthesia
  42. Active illicit substance abuse or alcoholism
  43. Current smoker
  44. Participating in another ongoing clinical trial of an investigational drug or device
  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 patient diary, or comply with study visits and other study procedures as required per protocol

    Additional eligibility criteria to be confirmed during the screening process:

  47. HbA1c post Run-In Phase < 7.5% (59 mmol/mol) or > 9.5% (86 mmol/mol)
  48. 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)
  49. 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)
  50. Mean of 3 separate blood pressure measurements >180 mmHg (systolic) or >100 mmHg (diastolic)
  51. Active and uncontrolled GERD defined as grade III esophagitis or greater
  52. Abnormalities of the GI tract preventing endoscopic access to the duodenum
  53. Anatomic abnormalities in the duodenum that would preclude the completion of the DMR procedure, including tortuous anatomy
  54. Malignancy newly diagnosed by endoscopy
  55. 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
Contact: Olga Ohayon +17816919275 olga@fractyl.com
Contact: Karen Hager +17819028840 Khager@fractyl.com

Locations
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, 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         
Sponsors and Collaborators
Fractyl Laboratories, Inc.

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: October 25, 2018
Last Verified: October 2018

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:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases