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

Sponsor

Metavention (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04285554

Collaborator

(none)

Enrollment

Locations

Arm

28.1

Anticipated Duration (Months)

1.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Device: iRF System Hepatic Denervation	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

The study is a prospective, single-arm, multi-center, non-randomized trialThe study is a prospective, single-arm, multi-center, non-randomized trial

Masking:

None (Open Label)

Primary Purpose:

Device Feasibility

Official Title:

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

Actual Study Start Date :

Jul 28, 2020

Actual Primary Completion Date :

Mar 2, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hepatic Denervation	Device: iRF System Hepatic Denervation 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).

Arm

Intervention/Treatment

Experimental: Hepatic Denervation

Device: iRF System Hepatic Denervation

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).

Outcome Measures

Primary Outcome Measures

Rate of Serious Adverse Device Effects [Index Procedure through 90 days]
The incidence rate of serious adverse device effects (SADEs) from time of Index Procedure through 90 days.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

22 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology, P.C.	Birmingham	Alabama	United States	35211
2	Stanford University Medical Center	Stanford	California	United States	94305
3	AdventHealth Translational Research Institute	Orlando	Florida	United States	32804
4	Prairie Education & Research Cooperative (PERC)	Springfield	Illinois	United States	62701
5	Metropolitan Cardiology Consultants	Coon Rapids	Minnesota	United States	55433
6	South Oklahoma Heart Research, LLC	Oklahoma City	Oklahoma	United States	73135
7	UPMC Pinnacle	Harrisburg	Pennsylvania	United States	17011
8	Soltero Cardiovascular Research Center	Dallas	Texas	United States	75226