Evaluation of the Integrated Radio Frequency Denervation System to Improve Glycemic Control in Type 2 Diabetic Subjects

Inclusion criteria

• Age ≥22 and ≤70 years old
• Type 2 diabetes diagnosis meeting the following criteria:

• HbA1c > 7.0% and ≤ 9.0% (53 mmol/mol - 75 mmol/mol), AND
• On at least two anti-diabetic medications; one at the highest tolerated dose with no changes in medication dose in the 12 weeks prior to the first screening visit
• Waist circumference ≥102 cm (male) and ≥88cm (female)
• Diagnosis of hypertension: SBP ≥140mmHg OR SBP ≥130mmHg on hypertension medication(s)
• Documented status of stable lifestyle modifications
• Women of childbearing potential (WOCBP) must be using at least one acceptable method of contraception throughout the study

Exclusion criteria

• BMI >40 kg/m2
• Diagnosis of type 1 diabetes
• Use of insulin within 90 days of consent
• Two or more self-reported or documented severe hypoglycemia events (severe hypoglycemia event defined as: hypoglycemia associated with severe cognitive impairment requiring external assistance for recovery) in the 180 days prior to Index Procedure
• One or more documented hyperglycemia episodes requiring hospitalization in the 180-days prior to Index Procedure
• During medication run in period, uncontrolled hyperglycemia noted by a fasting glucose value of >270mg/dL or >360mg/dL at any point that is then confirmed by a second measurement (not on the same day)
• A history of bariatric surgery, renal denervation, baroreflex activation therapy, or liver transplant, or these procedures are planned in the 365 days following Index Procedure
• Any surgical procedure within 30 days prior to Index Procedure
• History of or current symptomatic gallstones (e.g., cholecystitis, bile duct dilatation) without a cholecystectomy being performed (Note: subjects who have had a cholecystectomy are not excluded)
• Previous hepatobiliary surgery/intervention that in the opinion of the investigator could preclude the ability to perform denervation of the common hepatic artery
• Currently taking the following medications within 90 days prior to screening and/or there is a need or anticipated need for these medications during the study:

• Systemic corticosteroids
• Anticonvulsants
• Centrally acting sympatholytics
• Use of anticoagulation therapy which cannot be discontinued from 7 days before to 14 days after the Index Procedure
• Any other condition(s) that would compromise the safety of the Subject or compromise study quality as judged by the Investigator
• eGFR <45 mL/min/1.73 m2
• History or diagnosis of proliferative retinopathy or advanced autonomic neuropathy (e.g., orthostatic hypotension attributable to autonomic neuropathy, a diagnosis of gastroparesis, or a clinical history strongly suggestive of delayed gastric emptying)
• Myocardial infarction, unstable angina within 1 year prior to consent
• Widespread atherosclerosis with documented intravascular thrombosis or unstable plaques
• Documented history or concurrent signs of significant thyroid disease NOTE: If a subject is on chronic thyroid drug treatment, and has a serum TSH test result in normal range at Screening they may enter study
• Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count <100,000/microliter, or documented coagulopathy
• Significant alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g) in women and 3 drink units per day (equivalent to 30 g) in men, or inability to reliably quantify alcohol intake
• Active substance abuse, based on Investigator judgment, including inhaled or injected drugs, within 1 year prior to the initial screening
• Significant weight loss within the last 6 months (e.g., >10% total body weight loss)
• Hepatic decompensation defined as the presence of any of the following:

• Serum albumin less than 3.5 g/dL
• International normalized ratio (INR) greater than 1.4 (unless due to therapeutic anticoagulants)
• Total bilirubin greater than 2 mg/dL with the exception of Gilbert syndrome
• History of esophageal varices, ascites, or hepatic encephalopathy
• ALT or AST greater than 200 U/L
• Diagnosis of liver cirrhosis
• Chronic liver or biliary disease of the following etiology:

• History or diagnosis of Hepatitis B
• History or diagnosis of Hepatitis C
• History or diagnosis of current active autoimmune hepatitis
• History or diagnosis of primary biliary cholangitis (PBC)
• History or diagnosis of primary sclerosing cholangitis
• History or diagnosis of Wilson's disease
• History or diagnosis of alpha-1-antitrypsin deficiency
• History or diagnosis of hemochromatosis
• History or evidence of drug-induced liver disease, as defined on the basis of typical exposure and history
• Known bile duct obstruction
• Suspected or proven liver cancer
• History of acute or chronic pancreatitis
• Subjects unable to undergo CT for any reason
• Currently enrolled in any other investigational trial
• History of an acute neurologic event including epilepsy, seizures, stroke, and transient ischemic attack.
• Iliac/femoral artery stenosis precluding insertion of the catheter
• Human immunodeficiency virus (HIV)
• Subjects with a history of adverse reaction to heparin or heparin induced thrombocytopenia (HIT)
• Subjects with conditions that can affect RBC turnover, those who have received a blood transfusion in the past 90 days, or expect to have an elective procedure during the course of the study that may require blood transfusion
• Not a candidate for surgery or general anesthesia
• Unwilling to comply with study requirements, including medication run-in, SMBG, patient diary and follow-up visits
• Subjects with implantable pacemakers, implantable cardiac defibrillators or implantable neurostimulators

Anatomic Exclusions from CT Angiogram

• Replaced or accessory LHA or RHA determined on CT angiogram.
• Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the device from the femoral artery to the target location
• Evidence of CHA and/or portal vein intraluminal thrombus
• CHA vessel diameter <4.0mm or >7.0mm
• CHA diameter stenosis >30%
• CHA vessel length <20mm