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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Clinical Mechanism of Endovascular Denervation (EDN) for the Treatment of Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Device: Endovascular Denervation System (Netrod)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The endovascular denervation (EDN) group<br>Receive endovascular denervation (EDN) treatment | Device: Endovascular Denervation System (Netrod)<br>* The Netrod system is a percutaneous, catheter- based device which uses radiofrequency energy to denervate the sympathetic nerves surrounding the arteries<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of islet secretory function (HOMA-β) | Changes of islet secretory function (HOMA-β, HOMA-IR) from baseline at 6 months post procedure | From baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From baseline to 12 months post procedure | 
| Changes in Hba1c | Changes in Hba1c from baseline at 12 months post procedure | From baseline to 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 | From baseline to 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 | From baseline 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 | From baseline to 12 months post procedure | 
| Changes in liver fat content | Changes in liver fat content from baseline at 6 months post procedure | From baseline to 6 months post procedure | 
| Changes in liver function | Changes of liver function (ALT, AST, GGT, ALP) from baseline at 6 months post procedure | From baseline to 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 | From baseline to 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 | From baseline to 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 | From baseline to 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 | From baseline to 6 months post procedure | 
| 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 | From baseline to 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 | From baseline to 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 | From baseline to 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 | From baseline to 6 months post procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, Endovascular denervation