None listed
Conditions
Brief summary
Overactive SNS signaling to central metabolic organs, the kidneys and liver, can play a pivotal role in the development and progression of conditions associated with the MetS, including HTN and diabetes. Inhibition of this overactive sympathetic signaling, through intravascular denervation, is a proposed therapy to address these sympathetically mediated disorders. The purpose of the DeLIVER Study is to evaluate the safety of renal and hepatic denervation, in one procedure, using the Integrated Radio Frequency (iRF) Denervation System and to detect any improvement in controlling hypertension, blood sugar and other parameters involved in your metabolism following the denervation procedure.
Interventions
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) and the renal arteries while minimizing injury to the arterial wall. The iRF System consists of the following components:
1. Single-use, monopolar, iRF Catheter that contains four (4) electrodes; provided sterile
2. Reusable, Radiofrequency Generator (RFG) with an Integrated Syringe Pump
3. Single-use, Generator Accessory K
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) and the renal arteries while minimizing injury to the arterial wall. The iRF System consists of the following components: 1. Single-use, monopolar, iRF Catheter that contains four (4) electrodes; provided sterile 2. Reusable, Radiofrequency Generator (RFG) with an Integrated Syringe Pump 3. Single-use, Generator Accessory Kit that contains a Syringe Cassette, two (2) tubing sets, and a waste collection bag, provided sterile 4. Single-use, Extension Cable, provided sterile This procedure will be completed by an Interventional Cardiologist/Radiologist that has been trained on the device. It will occur in a catheterization laboratory or appropriate surgical setting. Up to 2 ablations will be administered during one procedure which will last no more than 2 hours. Clinical observation and monitoring by the treating physician of the iRF system will be conducted throughout the procedure. The generator will also display system progress. Each denervation cycle will provide 6 Watts of energy for 150 seconds to the common hepatic artery. Up to 2 cycles can be administered per procedure.
Sponsors
Metavention, Inc.
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
22 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1) Age greater than or equal to 22 and less than or equal to 70 years old 2) Waist circumference greater than or equal to 102 cm (male) and greater than or equal to 88 cm (female) 3) Office systolic blood pressure (SBP) greater than or equal to 140 mmHg and less than 180 mmHg on a stable dose of antihypertensive medication(s) for at least 30 days 4) Documented daytime systolic ambulatory blood pressure (ABP) greater than or equal to 135 and less than 175 mmHg 5) Documented status of stable lifestyle modifications 6) Willing to comply with study requirements, including follow-up visits 7) Women of childbearing potential (WOCBP) must be using at least one acceptable method of contraception throughout the study
Exclusion criteria
8) BMI of greater than 40 kg/m2 9) Type 1 diabetes mellitus or uncontrolled Type 2 diabetes (uncontrolled defined as HbA1c greater than 8.5 % / 69 mmol/mol) 10) One or more documented hyperglycemia episodes (requiring hospitalization) in the 90 days prior to Index Procedure 11) One or more severe hypoglycemic events (severe cognitive impairment requiring external assistance for recovery) in the 90 days prior to Index Procedure 12) One or more documented severe hypertensive crisis (persistent or elevated hypertension greater than 180 mmHg accompanied by clinical symptoms) in the 90 days prior to Index Procedure 13) 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 14) Any surgical procedure within 30 days prior to Index Procedure 15) 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) 16) Previous hepatobiliary surgery/intervention that in the opinion of the investigator could preclude the ability to perform denervation of the common hepatic artery 17) Use of anticoagulation therapy which cannot be discontinued from 7 days before to 14 days after the Index Procedure 18) Any other condition(s) that would compromise the safety of the Subject or compromise study quality as judged by the Investigator 19) eGFR less than 45 mL/min/1.73 m2 20) 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) 21) Myocardial infarction, unstable angina, stroke, or transient ischemic attack within the 180 days prior to Baseline, or has widespread atherosclerosis, with documented intravascular thrombosis or unstable plaques 22) Heart failure (New York Heart Association [NYHA] Class III-IV) at time of consent 23) Documented history of persistent or permanent atrial tachyarrhythmia 24) Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea 25) Night shift workers 26) Chronic regular use (e.g., daily use) of NSAIDs for 6 months or greater. Aspirin therapy is allowed. 27) Active implantable medical device (e.g., ICD or CRT-D, neuromodulator/spinal stimulator, baroreflex stimulator) 28) Known primary pulmonary HTN (greater 60 mmHg pulmonary artery or right ventricular systolic pressure) 29) Evidence of active infection within 7 days prior to Index Procedure 30) Documented history of chronic active inflammatory bowel disorders such as Crohn’s disease or ulcerative colitis 31) Individual has known pheochromocytoma, Cushing syndrome, primary hyperaldosteronism, coarctation of the aorta, untreated hyperthyroidism, untreated hypothyroidism, or primary hyperparathyroidism. (Note: Treated hyperthyroidism and treated hypothyroidism are permissible.) 32) Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count <100,000/microliter, or documented coagulopathy 33) Any known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements or whose participation may result in data analysis confounders 34) Significant weight loss within the last 6 months (e.g., greater than 10% total body weight loss) 35) Hepatic decompensation defined as the presence of any of the following: a) Serum albumin less than 3.5 g/dL b) International normalized ratio (INR) greater than 1.4 (unless due to therapeutic anticoagulants) c) Total bilirubin greater than 2 mg/dL with the exception of Gilbert syndrome d) History of esophageal varices, ascites, or hepatic encephalopathy 36) ALT or AST greater than 200 U/L 37) Diagnosis of liver cirrhosis 38) Chronic liver or biliary disease of the following etiology: a) Evidence of Hepatitis B note: subjects who have recovered from a past Hepatitis B infection and demonstrated negative for Hepatitis B surface antigen are not excluded b) History or evidence of Hepatitis C c) History or evidence of current active autoimmune hepatitis d) History or evidence of primary biliary cholangitis e) History or evidence of primary sclerosing cholangitis f) History or evidence of Wilson's disease g) History or evidence of alpha-1-antitrypsin deficiency h) History or evidence of hemochromatosis i) History or evidence of drug-induced liver disease, as defined on the basis of typical exposure and history j) Known bile duct obstruction k) Suspected or proven liver cancer 39) History of acute or chronic pancreatitis 40) Subjects unable to undergo CT for any reason 41) Currently enrolled in any other investigational trial (participation in non-interventional registries is acceptable) 42) History of epilepsy 43) Iliac/femoral artery stenosis precluding insertion of the catheter 44) Human Immunodeficiency Virus (HIV) 45) Pregnant, nursing, or planning to become pregnant (documented negative pregnancy test result required documented within a maximum of 7 days before Index Procedure for all women of childbearing potential) 46) Limited life expectancy of less than 1 year at the discretion of the investigator Anatomic Exclusions from CT Angiogram 47) Renal artery (RA) anatomy on either side or Common hepatic artery (CHA) anatomy, ineligible for treatment including the following: a) CHA or RA diameter less than 4.0 mm or greater than 7.0 mm b) CHA or RA length less than 20.0 mm c) Only one functioning kidney d) Presence of abnormal kidney tumors e) CHA or RA with aneurysm f) Pre-existing stent or history of angioplasty in target arteries g) Fibromuscular dysplasia of the CHA or renal arteries h) Presence of CHA or RA diameter stenosis greather than 30% i) Individual lacks appropriate arterial anatomy for effective treatment or for maneuvering of the device from the femoral artery to the target location(s)
Outcome results
None listed