ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12619001524189

Ethics application status

Approved

Date submitted

13/09/2019

Date registered

5/11/2019

Date last updated

25/05/2020

Date data sharing statement initially provided

5/11/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

The DeLIVER NZ study will evaluate the safety of the Integrated Radio Frequency (iRF) system which is designed to improve glycemic control in 30 type 2 diabetic patients.

Scientific title

A Prospective, Single-Arm, Multi-Center study of the Metavention Integrated Radio Frequency Nerve Ablation System to improve Hyperglycemia in Type II Diabetic Subjects in New Zealand

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

DeLIVER

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Type II Diabetes Mellitus

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The iRF System is a percutaneous, catheter-based device which uses RF energy to circumferentially ablate the sympathetic nerves surrounding the Common Hepatic Artery (CHA) while minimizing injury to the arterial wall. The iRF System consists of the following components:
1. Single-use, monopolar, Ablation 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

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.

Intervention code [1]

Treatment: Devices

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

The incidence rate of device related serious adverse device effects (SADEs) from time of Index Procedure through 90 days.
Some potential adverse events include but are not limited to: post operative pain, hematoma at the access site, tenderness and swelling at the catheter insertion site, allergic reaction to materials used, high or low blood pressure or damage to the liver. All events will be assessed using a variety of methods including: monitoring of vital signs, blood labs, glucose testing, imaging and self-reporting. Patients will be closely monitored by the study physician throughout study participation.

Timepoint [1]

90 days post procedure

Secondary outcome [1]

Glycemic control will be measured through blood labs of:
HbA1c

Timepoint [1]

30, 90, and 180 days post Index Procedure

Secondary outcome [2]

Change in Office Blood Pressure assessed while in the physicians office using their standard method of assessing blood pressure with a sphygmomanometer.

Timepoint [2]

30, 90, and 180 days post Index Procedure

Secondary outcome [3]

Change in liver MRI-PDFF

Timepoint [3]

90 and 180 days post Index Procedure

Secondary outcome [4]

Clinical and laboratory assessment changes in:
Waist circumference measured through clinical examination (using standard of care items, such as a measuring tape).

Timepoint [4]

30, 90, and 180 days post Index Procedure

Secondary outcome [5]

Adverse Event rate:
Summary of all reported adverse events during the study. At each follow-up visit, the investigator or designee will determine and report any adverse event occurrences using the Adverse Event Case Report From designed for this study. Adverse events can be reported at anytime throughout the study by the patient or study staff.

Timepoint [5]

180 days post Index Procedure

Secondary outcome [6]

Glycemic control will be measured through blood labs of:
Fructosamine

Timepoint [6]

30, 90, and 180 days post Index Procedure

Secondary outcome [7]

Glycemic control will be measured through blood labs of:
Fasting Plasma Glucose

Timepoint [7]

30, 90, and 180 days post Index Procedure

Secondary outcome [8]

Clinical and laboratory assessment changes in:
Alkaline phosphatase (ALP)

Timepoint [8]

30, 90, and 180 days post Index Procedure

Secondary outcome [9]

This is a composite outcome, using the 3 blood tests below.
Clinical and laboratory assessment changes in:
Mixed Meal Tolerance test (MMTT) measuring blood levels of the following taken at regular intervals 30 mins prior to meal and for 180 mins after:
glucose
insulin
C-peptide

Timepoint [9]

30, 90, and 180 days post Index Procedure

Secondary outcome [10]

Clinical and laboratory assessment changes in:
Blood levels of Triglycerides

Timepoint [10]

30, 90, and 180 days post Index Procedure

Secondary outcome [11]

Changes in hepatic function by assessing blood levels of:
Alanine aminotransferase (ALT)

Timepoint [11]

30, 90, and 180 days post Index Procedure

Secondary outcome [12]

Changes in hepatic functions by assessing blood levels of:
Aspartate aminotransferase (AST)

Timepoint [12]

30, 90, 180 days post Index Procedure

Secondary outcome [13]

Changes in hepatic function by assessing blood levels of:
Bilirubin (Total)

Timepoint [13]

30, 90, 180 days post Index Procedure

Secondary outcome [14]

Changes in hepatic functions by assessing blood levels of:
Albumin

Timepoint [14]

30, 90, 180 days post Index Procedure

Secondary outcome [15]

Changes in hepatic functions by assessing blood levels of:
Total protein (TP)

Timepoint [15]

30, 90, 180 days post Index Procedure

Secondary outcome [16]

Changes in hepatic functions by assessing blood levels of:
Globulin

Timepoint [16]

30, 90, 180 days post Index Procedure

Eligibility

Key inclusion criteria

Each subject must meet the following criteria to be eligible for this study:
1) Age greater than or equal to 22 and less than or equal to 65 years old
2) Type II Diabetes diagnosis:
a) Hb1Ac of 53 mmol/mol – 86 mmol/mol (7.0% – 10.0%)
b) On a consistent drug regimen of metformin or metformin/vildagliptin for at least 90 days prior to baseline
3) Diagnosis of the Metabolic Syndrome meeting the following parameters:
a) Waist circumference greater than or equal to 102 cm (male) and greater than or equal to 88 cm (female), AND
b) Fasting plasma triglycerides greater than or equal to1.8mmol/L (150 mg/dL) OR on medication for the treatment of high triglycerides, AND
c) Diagnosis of hypertension: SBP greater than or equal to 140 mmHg OR on 2 or fewer hypertension medications with SBP greater than or equal to 130 mmHg
4) Documented status of stable lifestyle modifications
5) Willing to comply with study requirements, including follow-up visits
6) Women of childbearing potential (WOCBP) must be using at least one acceptable method of contraception throughout the study

Minimum age

22 Years

Maximum age

65 Years

Gender

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Subjects who meet any of the following criteria will not be eligible to participate:
7) BMI >40 kg/m2.
8) Diagnosis of type 1 diabetes.
9) Current use of diabetes medications other than metformin and/or vildagliptin/metformin
10) Current use of >2 hypertension medications
11) Two or more self-reported or documented severe (>13.3 mmol/L fasting plasma glucose level and >16.7 mmol/L non-fasting plasma glucose hyperglycemia events in the 180 days prior to Baseline, or any hyperglycemia event from the time of Baseline until Index Procedure
12) A history of bariatric surgery, renal denervation, baroreflex activation therapy, or liver transplant, or these procedures are planned in the 180 days following Index Procedure
13) Any surgical procedure within 30 days prior to Index Procedure
14) History of gallstones without a cholecystectomy being performed or current gallstones (Note: subjects who have had a cholecystectomy are not excluded)
15) Previous hepatobiliary surgery/intervention that in the opinion of the investigator could preclude the ability to perform denervation of the common hepatic artery
16) 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:
a) Pioglitazone
b) High dose vitamin E (>400 IU/day)
c) Systemic Corticosteroids
d) Anticonvulsants
e) Centrally acting sympatholytics
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 <60 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) 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
23) Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count <100,000/microliter, or documented coagulopathy
24) 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
25) Active substance abuse, based on Investigator judgment, including inhaled or injected drugs, within 1 year prior to the initial screening
26) Significant weight loss within the last 6 months (e.g., >10% total body weight loss)
27) 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
28) ALT or AST greater than 200 U/L
29) Diagnosis of liver cirrhosis
30) Chronic liver or biliary disease of the following etiology:
a) History or evidence of Hepatitis B
b) History or evidence of Hepatitis C
c) History or evidence of current active autoimmune hepatitis
d) History or evidence of primary biliary cholangitis (PBC)
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
31) History of acute or chronic pancreatitis
32) Subjects unable to undergo MRI-PDFF or CT for any reasons:
33) Currently enrolled in any other investigational trial
34) History of epilepsy
35) Iliac/femoral artery stenosis precluding insertion of the catheter
36) Human immunodeficiency virus (HIV)
Anatomic Exclusions from CT Angiogram
37) Replaced or accessory LHA or RHA determined on CT Angiogram
38) Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the device from the femoral artery to the target location
39) Evidence of intraluminal thrombus
40) CHA vessel diameter <4.0mm or >7.0mm
41) CHA diameter stenosis >30%
42) CHA vessel length <20mm

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Not Applicable

Type of endpoint(s)

Safety/efficacy

Statistical methods / analysis

Descriptive Statistics

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

23/01/2020

Actual

5/03/2020

Date of last participant enrolment

Anticipated

30/06/2021

Actual

Date of last data collection

Anticipated

31/12/2021

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Metavention, Inc.

Address [1]

10900 73rd Avenue North
Maple Grove, MN 55369

Country [1]

United States of America

Primary sponsor type

Commercial sector/Industry

Name

Metavention, Inc.

Address

10900 73rd Avenue North
Maple Grove, MN 55369

Country

United States of America

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

New Zealand Northern B Health and Disabilities Ethics Committee

Ethics committee address [1]

Ministry of Health
Health and Disabilities Ethics Committee
P.O. Box 5013
Wellington, NZ 6140

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

19/09/2019

Approval date [1]

15/11/2019

Ethics approval number [1]

19/NTB/164/AM01

Summary

Brief summary

The liver plays a central role in regulating blood glucose levels. The nerves around the liver arteries play a role in stimulating the liver to release glucose in to the blood stream. The process of disrupting the liver artery nerves is called hepatic denervation or hepatic nerve ablation.
The purpose of the DeLIVER Study is to evaluate the safety of hepatic denervation using the integrated radio frequency (iRF) System and to detect any improvement in controlling blood sugar and other parameters involved in your metabolism following the hepatic denervation procedure.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Mark Webster

Address

Consultant Interventional Cardiologist
Green Lane Cardiovascular Service
Auckland City Hospital
Private Bag 92-024
Park Road, Grafton
Auckland 1142
New Zealand

Country

New Zealand

Phone

+6493670000

Fax

mwebster@adhb.govt.nz

Contact person for public queries

Name

Mrs Megan Brandt

Address

Metavention, Inc
10900 73rd Avenue North

Country

United States of America

Phone

+16128148204

Fax

deliver@metavention.com

Contact person for scientific queries

Name

Dr Mark Webster

Address

Consultant Interventional Cardiologist
Green Lane Cardiovascular Service
Auckland City Hospital
Private Bag 92-024
Park Road, Grafton
Auckland 1142
New Zealand

Country

New Zealand

Phone

+6493670000

Fax

mwebster@adhb.govt.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No other documents available

Summary results

No Results

Trial Review