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Endovascular Denervation (EDN) for the Treatment of Type 2 Diabetes Mellitus

Primary Purpose

Type 2 Diabetes Mellitus (T2DM)

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Endovascular Denervation System (Netrod)
Sponsored by
Zhongda Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus (T2DM) focused on measuring Type 2 Diabetes Mellitus, Endovascular denervation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subject with age of #18 years old and#75 years old (both ends included) Subject (or legal guardian) understands the requirements and treatment of this clinical trial and agrees to and is able to complete the trial Diagnosed with T2DM for ≤15 years (according to WHO criteria) On the basis of metformin (daily dose ≥1000mg), using a combination of 1-3 OADs for more than last 3 months, with or without insulin (dose not limited). Defined OADs were: sulfonylureas/ glienides, thiazolidinediones and α-glycosidase inhibitors Glycosylated hemoglobin (HbA1c) levels between 7.5% and 10.5% (based on baseline tests) Body mass index (BMI) ≥ 18 and ≤40kg/m2 Exclusion Criteria: T1DM or any secondary diabetes History of aortic disease (such as aortic aneurysm or aortic dissection) or aortic surgery (including celiac artery dissection) Baseline CTA examination revealed aortic aneurysm or aortic dissection, or abnormal anatomical structure of hepatic artery and its branches, or other vascular structure/status abnormalities (such as severe tortuosity or narrowing of the artery, endovascular thrombosis or unstable plaque, etc.) that were not suitable for endovascular denervation as determined by the researcher More than 2 self-reported or documented events of severe hypoglycemia (defined as hypoglycemia with severe cognitive impairment requiring assistance) within the past 6 months Patients who had a major cardiovascular and cerebrovascular event (MACCE), major surgery, severe infection, gastrointestinal bleeding, and acute pancreatitis in the past 6 months Severe autonomic neuropathy (postural hypotension, etc.) Severe liver insufficiency (ALT and/or AST above 3 times the normal upper limit or serum total bilirubin above 2 times the normal upper limit), renal insufficiency (eGFR < 60mL/ min/1.73m2). eGFR calculation formula is shown in Note e of Table 4.3 Data collection table.), chronic pancreatitis, cocoagulation disorder (PT, APTT or INR higher than 2 times of the normal upper limit; Platelet count < 80×109/L or ≥ 700×109/L) and malignant tumors Suffering from mental illness and unable to cooperate Pregnant There were conditions that the researchers determined will affect the safety of the subjects or interfere with the evaluation of the test results Patients not eligible for MRI (e.g. paramagnetic metal implants, claustrophobia, etc.) Participating in or currently participating in other clinical studies within 3 months prior to enrollment

Sites / Locations

  • Zhongda Hospital, Southeast UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

The endovascular denervation (EDN) group

Arm Description

Receive endovascular denervation (EDN) treatment

Outcomes

Primary Outcome Measures

Changes of islet secretory function (HOMA-β)
Changes of islet secretory function (HOMA-β, HOMA-IR) from baseline at 6 months post procedure

Secondary Outcome Measures

Incidence of device or procedure-related major adverse events
Incidence of device or procedure-related major adverse events from baseline to 12 months post procedure
Changes in Hba1c
Changes in Hba1c from baseline at 12 months post procedure
Changes in the time in range (TIR) over 14 days of glucose
Changes in the time in range (TIR) over 14 days of using continuous glucose monitoring at 12 months post procedure
Changes in the area under OGTT insulin release curve
Change in the area under OGTT insulin release curve from base line to 12 months post procedure
Changes in the area under OGTT C-peptide release curve
Changes in the area under OGTT C-peptide release curve from base line to 12 months post procedure
Changes in liver fat content
Changes in liver fat content from baseline at 6 months post procedure
Changes in liver function
Changes of liver function (ALT, AST, GGT, ALP) from baseline at 6 months post procedure
Changes in blood lipids
Changes in blood lipid as indicated by triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol from baseline at 12 months post procedure
Changes in the gastric emptying
Changes in the gastric emptying as indicated by 13C-acetate breath test from baseline at 12 months post procedure
Changes in insulin sensitivity
Changes in insulin sensitivity as indicated by glucose infusion rate and M value in hyperinsulinemic-euglycemic clamp from baseline at 6 months post procedure
Changes in metabolic-related hormones
Changes in metabolic-related hormones including glucagon, pancreatic polypeptide, glucagon-like peptide-1, gastric inhibitory polypeptide, neuropeptide Y, peptide YY, ghrelin, adiponectin and leptin
Changes in plasma cytokines
Changes in plasma cytokines including IFN-γ、IL-1β、IL-2、IL-4、IL-6、IL-10、IL-12p70、IL-17A、TNF-α、IL-13、IL-15、MCP-1、FGF21/23 and BDNF from baseline at 6 months post procedure
Changes in blood and fecal metabolome
Changes in blood and fecal metabolome (Using liquid-mass combination (LC - MS) method) from baseline at 6 months post procedure
Changes in fecal microbiota
Changes in fecal microbiota (Using liquid-mass combination (LC - MS) method assess fecal 16S-rRNA sequencing and non-targeted metabolomics) from baseline at 6 months post procedure
Change of sympathetic nervous system activity
Change of sympathetic nervous system activity (cardiac strain capacity was evaluated by autonomic nervous function and Cardiopulmonary resonance assesses sympathetic nervous system excitability) from baseline at 6 months post procedure

Full Information

First Posted
November 28, 2022
Last Updated
July 20, 2023
Sponsor
Zhongda Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05673668
Brief Title
Endovascular Denervation (EDN) for the Treatment of Type 2 Diabetes Mellitus
Official Title
Clinical Mechanism of Endovascular Denervation (EDN) for the Treatment of Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 27, 2022 (Actual)
Primary Completion Date
October 30, 2023 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhongda Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective, single-center, single-arm, self-controlled study to evaluate the effects of endovascular denervation (EDN) on insulin secretory function and insulin sensitivity in the treatment of type 2 diabetes mellitus (T2DM) .
Detailed Description
This is a prospective, single-center, single-arm, self-controlled study. Patients with diagnosed T2DM and poor glycemic control (i.e.. glycated hemoglobin A1c (HbA1c) between 7.5% and 10.5% despite one to three oral antidiabetic drugs (OAD) and/or insulin on the basis of metformin. All included subjects will accept EDN treatment and were followed up at 7, 30 days and 3, 6, 12 months. The primary objectives were evaluate the effects of EDN on insulin secretory function and insulin sensitivity in the treatment of T2DM.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus (T2DM)
Keywords
Type 2 Diabetes Mellitus, Endovascular denervation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
The endovascular denervation (EDN) group
Arm Type
Experimental
Arm Description
Receive endovascular denervation (EDN) treatment
Intervention Type
Device
Intervention Name(s)
Endovascular Denervation System (Netrod)
Intervention Description
The Netrod system is a percutaneous, catheter- based device which uses radiofrequency energy to denervate the sympathetic nerves surrounding the arteries
Primary Outcome Measure Information:
Title
Changes of islet secretory function (HOMA-β)
Description
Changes of islet secretory function (HOMA-β, HOMA-IR) from baseline at 6 months post procedure
Time Frame
From baseline to 6 months
Secondary Outcome Measure Information:
Title
Incidence of device or procedure-related major adverse events
Description
Incidence of device or procedure-related major adverse events from baseline to 12 months post procedure
Time Frame
From baseline to 12 months post procedure
Title
Changes in Hba1c
Description
Changes in Hba1c from baseline at 12 months post procedure
Time Frame
From baseline to 12 months post procedure
Title
Changes in the time in range (TIR) over 14 days of glucose
Description
Changes in the time in range (TIR) over 14 days of using continuous glucose monitoring at 12 months post procedure
Time Frame
From baseline to 12 months post procedure
Title
Changes in the area under OGTT insulin release curve
Description
Change in the area under OGTT insulin release curve from base line to 12 months post procedure
Time Frame
From baseline to 12 months post procedure
Title
Changes in the area under OGTT C-peptide release curve
Description
Changes in the area under OGTT C-peptide release curve from base line to 12 months post procedure
Time Frame
From baseline to 12 months post procedure
Title
Changes in liver fat content
Description
Changes in liver fat content from baseline at 6 months post procedure
Time Frame
From baseline to 6 months post procedure
Title
Changes in liver function
Description
Changes of liver function (ALT, AST, GGT, ALP) from baseline at 6 months post procedure
Time Frame
From baseline to 6 months post procedure
Title
Changes in blood lipids
Description
Changes in blood lipid as indicated by triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol from baseline at 12 months post procedure
Time Frame
From baseline to 12 months post procedure
Title
Changes in the gastric emptying
Description
Changes in the gastric emptying as indicated by 13C-acetate breath test from baseline at 12 months post procedure
Time Frame
From baseline to 12 months post procedure
Title
Changes in insulin sensitivity
Description
Changes in insulin sensitivity as indicated by glucose infusion rate and M value in hyperinsulinemic-euglycemic clamp from baseline at 6 months post procedure
Time Frame
From baseline to 6 months post procedure
Title
Changes in metabolic-related hormones
Description
Changes in metabolic-related hormones including glucagon, pancreatic polypeptide, glucagon-like peptide-1, gastric inhibitory polypeptide, neuropeptide Y, peptide YY, ghrelin, adiponectin and leptin
Time Frame
From baseline to 6 months post procedure
Title
Changes in plasma cytokines
Description
Changes in plasma cytokines including IFN-γ、IL-1β、IL-2、IL-4、IL-6、IL-10、IL-12p70、IL-17A、TNF-α、IL-13、IL-15、MCP-1、FGF21/23 and BDNF from baseline at 6 months post procedure
Time Frame
From baseline to 6 months post procedure
Title
Changes in blood and fecal metabolome
Description
Changes in blood and fecal metabolome (Using liquid-mass combination (LC - MS) method) from baseline at 6 months post procedure
Time Frame
From baseline to 6 months post procedure
Title
Changes in fecal microbiota
Description
Changes in fecal microbiota (Using liquid-mass combination (LC - MS) method assess fecal 16S-rRNA sequencing and non-targeted metabolomics) from baseline at 6 months post procedure
Time Frame
From baseline to 6 months post procedure
Title
Change of sympathetic nervous system activity
Description
Change of sympathetic nervous system activity (cardiac strain capacity was evaluated by autonomic nervous function and Cardiopulmonary resonance assesses sympathetic nervous system excitability) from baseline at 6 months post procedure
Time Frame
From baseline to 6 months post procedure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject with age of #18 years old and#75 years old (both ends included) Subject (or legal guardian) understands the requirements and treatment of this clinical trial and agrees to and is able to complete the trial Diagnosed with T2DM for ≤15 years (according to WHO criteria) On the basis of metformin (daily dose ≥1000mg), using a combination of 1-3 OADs for more than last 3 months, with or without insulin (dose not limited). Defined OADs were: sulfonylureas/ glienides, thiazolidinediones and α-glycosidase inhibitors Glycosylated hemoglobin (HbA1c) levels between 7.5% and 10.5% (based on baseline tests) Body mass index (BMI) ≥ 18 and ≤40kg/m2 Exclusion Criteria: T1DM or any secondary diabetes History of aortic disease (such as aortic aneurysm or aortic dissection) or aortic surgery (including celiac artery dissection) Baseline CTA examination revealed aortic aneurysm or aortic dissection, or abnormal anatomical structure of hepatic artery and its branches, or other vascular structure/status abnormalities (such as severe tortuosity or narrowing of the artery, endovascular thrombosis or unstable plaque, etc.) that were not suitable for endovascular denervation as determined by the researcher More than 2 self-reported or documented events of severe hypoglycemia (defined as hypoglycemia with severe cognitive impairment requiring assistance) within the past 6 months Patients who had a major cardiovascular and cerebrovascular event (MACCE), major surgery, severe infection, gastrointestinal bleeding, and acute pancreatitis in the past 6 months Severe autonomic neuropathy (postural hypotension, etc.) Severe liver insufficiency (ALT and/or AST above 3 times the normal upper limit or serum total bilirubin above 2 times the normal upper limit), renal insufficiency (eGFR < 60mL/ min/1.73m2). eGFR calculation formula is shown in Note e of Table 4.3 Data collection table.), chronic pancreatitis, cocoagulation disorder (PT, APTT or INR higher than 2 times of the normal upper limit; Platelet count < 80×109/L or ≥ 700×109/L) and malignant tumors Suffering from mental illness and unable to cooperate Pregnant There were conditions that the researchers determined will affect the safety of the subjects or interfere with the evaluation of the test results Patients not eligible for MRI (e.g. paramagnetic metal implants, claustrophobia, etc.) Participating in or currently participating in other clinical studies within 3 months prior to enrollment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhi Wang, MD
Phone
+8618652918783
Email
wangzhiseu@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gaojun Teng, MD
Organizational Affiliation
Zhongda Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhongda Hospital, Southeast University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gaojun Teng, MD

12. IPD Sharing Statement

Learn more about this trial

Endovascular Denervation (EDN) for the Treatment of Type 2 Diabetes Mellitus

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