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

Type 2 Diabetes Mellitus (T2DM) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05673668
• Other study ID #: EDN-T2DM
• Status: Recruiting
• Phase: N/A
• Start date: December 27, 2022
• Est. completion date: April 30, 2024

Study information

• Verified date: July 2023
• Source: Zhongda Hospital
• Contact: Zhi Wang, MD
• Phone: +8618652918783
• Email: wangzhiseu[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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) .

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 information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 30, 2024
• Est. primary completion date: October 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 a-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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus (T2DM)

Intervention

Device:
• Endovascular Denervation System (Netrod)
The Netrod system is a percutaneous, catheter- based device which uses radiofrequency energy to denervate the sympathetic nerves surrounding the arteries

Locations

Country	Name	City	State
China	Zhongda Hospital, Southeast University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Zhongda Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of islet secretory function (HOMA-ß)	Changes of islet secretory function (HOMA-ß, HOMA-IR) from baseline at 6 months post procedure	From baseline to 6 months
Secondary	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
Secondary	Changes in Hba1c	Changes in Hba1c from baseline at 12 months post procedure	From baseline to 12 months post procedure
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes in liver fat content	Changes in liver fat content from baseline at 6 months post procedure	From baseline to 6 months post procedure
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes in plasma cytokines	Changes in plasma cytokines including IFN-??IL-1ß?IL-2?IL-4?IL-6?IL-10?IL-12p70?IL-17A?TNF-a?IL-13?IL-15?MCP-1?FGF21/23 and BDNF from baseline at 6 months post procedure	From baseline to 6 months post procedure
Secondary	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
Secondary	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
Secondary	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