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

Study Overview
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Brief Summary
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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.

Official Title
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A Prospective, Single-Arm, Multi-Center Study of the Metavention Integrated Radio Frequency Denervation System to Improve Glycemic Control in Type 2 Diabetic Subjects

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Device: iRF System Hepatic Denervation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: The study is a prospective, single-arm, multi-center, non-randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hepatic Denervation<br> | Device: iRF System Hepatic Denervation<br>* The iRF System is a percutaneous, catheter-based device which uses RF energy to circumferentially denervate the sympathetic nerves surrounding the common hepatic artery (CHA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Serious Adverse Device Effects | The incidence rate of serious adverse device effects (SADEs) from time of Index Procedure through 90 days. | Index Procedure through 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glycemic control: HbA1c | Change from baseline in glycemic control as indicated by HbA1c blood test | 30, 90, 180 and 365 days | 
| Change in glycemic control - FPG | Change from baseline in glycemic control as indicated by fasting plasma glucose blood test | 30, 90, 180 and 365 days | 
| Change in glycemic control - Insulin | Change from baseline in glycemic control as indicated by insulin blood test during Mixed Meal Tolerance Test | 30, 90, 180 and 365 days | 
| Change in glycemic control - C-peptide | Change from baseline in glycemic control as indicated by c-peptide blood test during Mixed Meal Tolerance Test | 30, 90, 180 and 365 days | 
| Change in office blood pressure | Change from baseline in office blood pressure: systolic and diastolic | 30, 90, 180 and 365 days | 
| Change in liver steatosis | Change from baseline in liver steatosis from baseline as measured using MRI-PDFF | 90 and 365 days | 
| Adverse Event rate 365 days | Adverse Event rate: Summary of all reported adverse events during the study | Consent through 365 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic Syndrome, NAFLD, Hypertension, High Blood Pressure, Glycemic Control, Diabetes, Denervation, Sympathetic Nervous System