Diagnosis of Type-1 Diabetes.
History of diabetic ketoacidosis or hyperosmola nonketotic coma.
Probable insulin production failure, defined as fasting C Peptide serum <1 ng/mL (333pmol/l).
Current or previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes) in the last 2 years.
Hypoglycemia unawareness.
History of severe hypoglycemia (more than 1 severe hypoglycemic event, as defined by need for third-party assistance, in the last 6 months from the screening visit).
Known autoimmune disease, as evidenced by a positive anti-glutamic acid decarboxylase (GAD) test, including but not limited to celiac disease, duodenal Crohn disease or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other systemic autoimmune connective tissue disorder. (Participants with adequately controlled primary hypothyroidism may be included).
Previous GI surgery that could limit treatment of the duodenum such as Billroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions. (Prior laparoscopic sleeve gastrectomy (LSG) will not be an exclusion).
History of chronic or acute pancreatitis.
History of, or gastrointestinal symptoms suggestive of diabetic gastroparesis.
Known active hepatitis or active liver disease other than NASH/NAFLD.
Acute gastrointestinal illness in the previous 7 days.
Known history of severe irritable bowel syndrome, radiation enteritis or other inflammatory bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease and Celiac disease.
Alcoholic liver disease, as indicated by ANI>0.
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 moderate-severe (Grade C or D) esophagitis, dysphagia due to achalasia or stricture/stenosis, esophageal varices, esophageal perforation, or any other disorder of the esophagus.
Upper gastrointestinal conditions such as active ulcers, polyps, varices, strictures, congenital or acquired duodenal telangiectasia.
Current use of anticoagulation therapy (such as warfarin) that cannot be discontinued for 7 days before and 14 days after the procedure.
Current use of P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) that cannot be discontinued for 14 days before and 14 days after the procedure.
Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during treatment through 4 weeks following the procedure. Use of acetaminophen and low dose aspirin is allowed.
Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 12 weeks prior to the baseline visit.
Use of drugs known to affect GI motility (e.g. Metoclopramide).
Use of weight loss medications such as Sibutramine (e.g. Meridia), Orlistat (e.g. Xenical), Phentermine or over-thecounter weight loss medications (prescription medication).
Currently taking, or unable to stop taking dietary supplements or herbal agents, including vitamin C or multivitamins containing vitamin C at >500 mg per day, multivitamins containing biotin (vitamin B7), and supplements for hair, skin, and nail growth. Multivitamins not containing biotin are permitted.
Persistent anemia, defined as hemoglobin <10g/dl.
Significant cardiovascular disease, including known history of valvular disease, or myocardial infarction, heart failure, transient ischemic attack, or stroke within 6 months prior to the Screening Visit.
Mean of 3 separate blood pressure measurements >180 mmHg (systolic) or >100 mmHg (diastolic).
Estimated glomerular filtration rate (eGFR) ≤ 60 ml/min/1.73m2 (estimated by MDRD).
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 participant a poor candidate for clinical trial participation in the opinion of the investigator.
History of secondary hypothyroidism or inadequately controlled primary hypothyroidism (TSH value outside normal range at screening).
Not a candidate for upper GI endoscopy or general anesthesia.
Active illicit substance abuse or alcoholism (>2 drinks/day regularly).
Active malignancy within the last 5 years (excluding nonmelanoma skin cancers).
Women breastfeeding.
Participating in another ongoing clinical trial of an investigational drug or device.
Any other mental or physical condition which, in the opinion of the study investigator, makes the participant a poor candidate for clinical trial participation.
Critically ill or has a life expectancy <3 years.
Use of heart pacemaker, duodenal metallic implants or other electronic device implants.
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.
The following additional exclusion criteria needs to be confirmed prior to initiating the RF ablation procedure:
Hb A1C post Run-In Phase < 7.5% (58 mmol/mol) or > 10.0 % (86 mmol/mol).
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.
CGM readings <54 mg/dl in more than 1% of time by CGM since the screening visit.
CGM readings > 360 mg/dL in more than 1% of time.
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 Run-In Period and confirmed by a second measurement (not on the same day).
Mean of 3 separate blood pressure measurements >180 mmHg (systolic) or >100 mmHg (diastolic).
Active and uncontrolled GERD defined as LonorA grade C erosive esophagitis or greater.
Abnormalities of the GI tract preventing endoscopic access to the duodenum.
Anatomic abnormalities in the duodenum that would, in the opinion of the investigator, preclude the completion of the RFV Ablation procedure, including tortuous anatomy.
Endoscopic observation of upper gastrointestinal abnormality such as ulcers, varices, strictures, intestinal telangiectasia.
Malignancy newly diagnosed by endoscopy.
For WOCBP: Positive urine pregnancy test or breast feeding.