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

Not Applicable
Recruiting
Conditions
Type 2 Diabetes Mellitus (T2DM)
Interventions
Device: Endovascular Denervation System (Netrod)
Registration Number
NCT05673668
Lead Sponsor
Zhongda Hospital
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
Inclusion Criteria
  1. Subject with age of #18 years old and#75 years old (both ends included)
  2. Subject (or legal guardian) understands the requirements and treatment of this clinical trial and agrees to and is able to complete the trial
  3. Diagnosed with T2DM for ≤15 years (according to WHO criteria)
  4. 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
  5. Glycosylated hemoglobin (HbA1c) levels between 7.5% and 10.5% (based on baseline tests)
  6. Body mass index (BMI) ≥ 18 and ≤40kg/m2
Exclusion Criteria
  1. T1DM or any secondary diabetes
  2. History of aortic disease (such as aortic aneurysm or aortic dissection) or aortic surgery (including celiac artery dissection)
  3. 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
  4. 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
  5. Patients who had a major cardiovascular and cerebrovascular event (MACCE), major surgery, severe infection, gastrointestinal bleeding, and acute pancreatitis in the past 6 months
  6. Severe autonomic neuropathy (postural hypotension, etc.)
  7. 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
  8. Suffering from mental illness and unable to cooperate
  9. Pregnant
  10. There were conditions that the researchers determined will affect the safety of the subjects or interfere with the evaluation of the test results
  11. Patients not eligible for MRI (e.g. paramagnetic metal implants, claustrophobia, etc.)
  12. Participating in or currently participating in other clinical studies within 3 months prior to enrollment

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
The endovascular denervation (EDN) groupEndovascular Denervation System (Netrod)Receive endovascular denervation (EDN) treatment
Primary Outcome Measures
NameTimeMethod
Changes of islet secretory function (HOMA-β)From baseline to 6 months

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

Secondary Outcome Measures
NameTimeMethod
Changes in the time in range (TIR) over 14 days of glucoseFrom baseline to 12 months post procedure

Changes in the time in range (TIR) over 14 days of using continuous glucose monitoring at 12 months post procedure

Changes in liver fat contentFrom baseline to 6 months post procedure

Changes in liver fat content from baseline at 6 months post procedure

Changes in liver functionFrom baseline to 6 months post procedure

Changes of liver function (ALT, AST, GGT, ALP) from baseline at 6 months post procedure

Incidence of device or procedure-related major adverse eventsFrom baseline to 12 months post procedure

Incidence of device or procedure-related major adverse events from baseline to 12 months post procedure

Changes in the area under OGTT insulin release curveFrom baseline to 12 months post procedure

Change in the area under OGTT insulin release curve from base line to 12 months post procedure

Changes in blood lipidsFrom baseline to 12 months post procedure

Changes in blood lipid as indicated by triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol from baseline at 12 months post procedure

Changes in Hba1cFrom baseline to 12 months post procedure

Changes in Hba1c from baseline at 12 months post procedure

Changes in the area under OGTT C-peptide release curveFrom baseline to 12 months post procedure

Changes in the area under OGTT C-peptide release curve from base line to 12 months post procedure

Changes in the gastric emptyingFrom baseline to 12 months post procedure

Changes in the gastric emptying as indicated by 13C-acetate breath test from baseline at 12 months post procedure

Changes in metabolic-related hormonesFrom baseline to 6 months post procedure

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 insulin sensitivityFrom baseline to 6 months post procedure

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 plasma cytokinesFrom baseline to 6 months post procedure

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 fecal microbiotaFrom baseline to 6 months post procedure

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 activityFrom baseline to 6 months post procedure

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

Changes in blood and fecal metabolomeFrom baseline to 6 months post procedure

Changes in blood and fecal metabolome (Using liquid-mass combination (LC - MS) method) from baseline at 6 months post procedure

Trial Locations

Locations (1)

Zhongda Hospital, Southeast University

🇨🇳

Nanjing, Jiangsu, China

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