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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

About

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.

Primary Purpose
Treatment
Study Type
Interventional
Phase
N/A

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
21 Years
Maximum Age
70 Years

Inclusion Criteria:

  • Male, and non-pregnant, non-lactating females
  • Age between 21 and 70 years (both inclusive)
  • 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
  • Glycosylated hemoglobin A1c (HbA1c) of 7.5-10% (both inclusive)
  • Body mass index (BMI) > 24 to ≤ 40 kg/m^2
  • 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.
  • Able to sign an informed consent form and comply with study requirements

Exclusion Criteria:

  • FPG >270 mg/dL
  • Known case of absolute insulin deficiency as indicated by clinical assessment a fasting plasma C-peptide of <0.6 ng/ml
  • Subjects on any other class of glucose-lowering agents other than GLAs listed in inclusion criteria
  • 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
  • Recurrent or severe urinary tract or genital mycotic infections or history of genitourinary infection within 4 weeks prior to informed consent
  • ALT or AST >3 times upper limit normal values
  • Use of an investigational drug within 1 month or 5 half-lives (whichever is longer) before the screening
  • Diagnosed with type 1 diabetes or with a recent history of ketoacidosis
  • Ketosis-prone T2D
  • Known diabetes related non-healing diabetic ulcers or amputations
  • History of more than 1 severe hypoglycemia episode or hypoglycemia unawareness within past 6 months
  • 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
  • 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
  • Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid stimulating hormone [TSH] value outside the normal range at screening)
  • Known history of thyroid cancer or hyperthyroidism with treatment within the past 12 months or inadequately controlled hyperthyroidism
  • An uncontrolled endocrine condition such as multiple endocrine neoplasia (except T2D)
  • 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)
  • 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
  • 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
  • Known history of chronic pancreatitis or a recent history of acute pancreatitis within the past year
  • 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
  • Symptomatic gallstones, symptomatic kidney stones, or acute cholecystitis
  • Clinically active systemic infection
  • 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
  • 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)
  • Known active coagulopathy or current upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, or congenital or acquired intestinal telangiectasia
  • Known cases of anemia, thalassemia, or conditions that affect red blood cell (RBC) turnover such as a recent blood transfusion within 90 days
  • 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
  • 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
  • Use of non-GLA drugs known to affect GI motility (e.g., metoclopramide)
  • 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
  • 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
  • History of new or worsening signs or symptoms of coronary heart disease (CHD) within the last 3 months
  • Known case of severe peripheral vascular disease, disease, defined as AMA Criteria Class 1 or greater
  • Known case of symptomatic heart failure with reduced ejection fraction (NYHA Class II-IV) requiring pharmacologic therapy to control symptoms
  • 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
  • Subjects who are at risk of pancreatitis, particularly those with a recent fasting triglyceride value of >600 mg/dL within the past 3 months
  • Actively participating in a weight-loss program and currently not in the maintenance phase
  • 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
  • History of substance use disorder based on the DSM-5 criteria within the last 12 months.
  • 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
  • Use of dietary supplements or herbal preparations that may have unknown effects on glycemic control or risk of bleeding
  • Participating in another ongoing clinical trial of an investigational drug or device
  • 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
  • Any other mental or physical condition which, in the opinion of the investigator, makes the subject a poor candidate for clinical-trial participation
  • Unwilling or unable to perform SMBG, complete the subject glycemia diary, or comply with study visits and other study procedures as required per protocol
  • 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)

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Study Stats
Protocol No.
21-001671
Category
Endocrine and Metabolic Disorders
Contact
Adreanne Rivera
Location
  • UCLA Santa Monica
  • UCLA Westwood
For Providers
NCT No.
NCT04419779
For detailed technical eligibility, visit ClinicalTrials.gov.