Overview

The objective of this early feasibility study is to evaluate the safety and performance of intravascular hepatic denervation using the Metavention Integrated Radio Frequency Denervation System (iRF System) to improve glycemic control in type 2 diabetes subjects.

Eligibility

Inclusion Criteria:

1. Age 22 and 65 years old
2. Type 2 Diabetes diagnosis meeting the following criteria:
3. Hb1Ac > 7.0% and 9.0% (53 mmol/mol - 75 mmol/mol), AND
4. On two OAD medications; one at the highest tolerated dose with no changes in medication dose in the 12 weeks prior to the first screening visit
5. Waist circumference 102 cm (male) and 88cm (female)
6. Diagnosis of hypertension: SBP 140mmHg OR SBP 130mmHg on hypertension medications (2 or less)
7. MRI-PDFF 10% indicating non-alcoholic fatty liver disease (NAFLD)
8. Documented status of stable lifestyle modifications
9. Women of childbearing potential (WOCBP) must be using at least one acceptable method of contraception throughout the study

Exclusion Criteria:

1. BMI >40 kg/m2
2. Diagnosis of type 1 diabetes
3. Current or previous use of injectable diabetes medications (e.g., insulin and GLP-1RA)
4. Current use of >2 hypertension medications
5. 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
6. One or more documented hyperglycemia episodes requiring hospitalization in the 180-days prior to Index Procedure
7. 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)
8. 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
9. Any surgical procedure within 30 days prior to Index Procedure
10. History of gallstones without a cholecystectomy being performed or current gallstones (Note: subjects who have had a cholecystectomy are not excluded)
11. Previous hepatobiliary surgery/intervention that in the opinion of the investigator could preclude the ability to perform denervation of the common hepatic artery
12. 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:
13. Systemic Corticosteroids
14. Anticonvulsants
15. Centrally acting sympatholytics
16. Use of anticoagulation therapy which cannot be discontinued from 7 days before to 14 days after the Index Procedure
17. Any other condition(s) that would compromise the safety of the Subject or compromise study quality as judged by the Investigator
18. eGFR <60 mL/min/1.73 m2
19. 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)
20. Unstable cardiovascular disease, myocardial infarction, unstable angina, widespread atherosclerosis with documented intravascular thrombosis or unstable plaques
21. 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 Baseline they may enter study
22. Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count <100,000/microliter, or documented coagulopathy
23. 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
24. Active substance abuse, based on Investigator judgment, including inhaled or injected drugs, within 1 year prior to the initial screening
25. Significant weight loss within the last 6 months (e.g., >10% total body weight loss)
26. Hepatic decompensation defined as the presence of any of the following:
27. Serum albumin less than 3.5 g/dL
28. International normalized ratio (INR) greater than 1.4 (unless due to therapeutic anticoagulants)
29. Total bilirubin greater than 2 mg/dL with the exception of Gilbert syndrome
30. History of esophageal varices, ascites, or hepatic encephalopathy
31. ALT or AST greater than 200 U/L
32. Diagnosis of liver cirrhosis
33. Chronic liver or biliary disease of the following etiology:
34. History or diagnosis of Hepatitis B
35. History or diagnosis of Hepatitis C
36. History or diagnosis of current active autoimmune hepatitis
37. History or diagnosis of primary biliary cholangitis (PBC)
38. History or diagnosis of primary sclerosing cholangitis
39. History or diagnosis of Wilson's disease
40. History or diagnosis of alpha-1-antitrypsin deficiency
41. History or diagnosis of hemochromatosis
42. History or evidence of drug-induced liver disease, as defined on the basis of typical exposure and history
43. Known bile duct obstruction
44. Suspected or proven liver cancer
45. History of acute or chronic pancreatitis
46. Subjects unable to undergo MRI-PDFF or CT for any reason
47. Currently enrolled in any other investigational trial
48. History of an acute neurologic event including epilepsy, seizures, stroke, and transient ischemic attack.
49. Iliac/femoral artery stenosis precluding insertion of the catheter
50. Human immunodeficiency virus (HIV)
51. Subjects with a history of adverse reaction to heparin or heparin induced thrombocytopenia (HIT)
52. 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
53. Not a candidate for surgery or general anesthesia
54. Unwilling to comply with study requirements, including medication run-in, SMBG, patient diary and follow-up visits
55. Subjects with implantable pacemakers, implantable cardiac defibrillators or implantable neurostimulators Anatomic Exclusions from CT Angiogram
56. Replaced or accessory LHA or RHA determined on CT angiogram.
57. Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the device from the femoral artery to the target location
58. Evidence of CHA and/or portal vein intraluminal thrombus
59. CHA vessel diameter <4.0mm or >7.0mm
60. CHA diameter stenosis >30%
61. CHA vessel length <20mm