The MILESTONE Study

Not Applicable

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Device: Endovascular Denervation

• Registration Number: NCT04086043
• Lead Sponsor: Zhongda Hospital

Brief Summary

Sympathetic overactivity induces insulin resistance and type 2 diabetes mellitus (T2DM), so it is assumed that denervation might reduce sympathetic overactivity and improve glucose metabolism and insulin sensitivity. The purpose of this study is to evaluate the effects of multi-electrode catheter-based endovascular denervation on glucose metabolism and insulin sensitivity in patients with T2DM.

Detailed Description

Sympathetic overactivity induces insulin resistance and type 2 diabetes mellitus (T2DM), so it is assumed that denervation might improve glucose metabolism and insulin sensitivity. Some clinical studies have shown that glucose metabolism is improved in patients with resistant hypertension both 1 and 3 months after denervation, and fasting glucose, insulin and C-peptide decreased significantly as did insulin resistance assessed by HOMA-IR. But in some clinical studies, denervation did not lead to a significant improvement of insulin sensitivity ≤12 months after treatment, and no effect in systemic sympathetic activity was observed after denervation. Therefore, the efficacy of denervation on glucose metabolism is still in controversy. The investigators wish to investigate the effect of multi-electrode catheter-based endovascular denervation on glucose metabolism and insulin sensitivity in patients with T2DM.

Study Timeline

• Status Verified: 2019-09
• Study First Submitted: 2019-09-05
• Study Start: 2019-09-10
• Study First Submitted QC: 2019-09-10
• Last Update Submitted: 2019-09-10
• Study First Posted: 2019-09-11
• Last Update Posted: 2019-09-11
• Primary Completion: 2022-09-09
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Over 18 years and ≤ 70 years old
• Able and willing to provide informed consent
• Patients with established type II diabetes mellitus (HbA1C>7.5%, diet or oral hypoglycaemic agents)
• Clinical stable as demonstrated by no change in background anti-diabetic medication in the last 30 days.
• Anticipated that patients are able to maintain a stable dose of medication for the duration of the study

Exclusion Criteria

• Arterial anatomy ineligible for endovascular denervation
• History of prior renal artery intervention including balloon angioplasty, stenting or previous renal denervation
• Type 1 diabetes mellitus
• Pregnant, nursing or planning to be pregnant
• Orthostatic hypotension
• eGFR <30 ml/min (MDRD formula)
• Patients that have allergy to contrast agent
• Myocardial infarction, unstable angina pectoris, coronary bypass or percutaneous angioplasty within 3 months before inclusion
• Cerebrovascular accidents and alimentary tract hemorrhage within 3 months before inclusion
• Any medical condition which, in the investigators opinion, may adversely affect the participants safety in the trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Endovascular Denervation	Endovascular Denervation	-

Primary Outcome Measures

Name	Time	Method
Changes in Oral Glucose Tolerance Test from baseline to 6 months	6 months	To investigate the influence of endovascular denervation on Oral Glucose Tolerance Test (OGTT).
Changes in glycosylated hemoglobin from baseline to 6 months	6 months	To investigate the influence of endovascular denervation on glycosylated hemoglobin (HbA1c).

Secondary Outcome Measures

Name	Time	Method
Changes in glycosylated hemoglobin up to 2 years	3, 12 and 24 months	To investigate the influence of endovascular denervation on glycosylated hemoglobin (HbA1c).
Changes in Oral Glucose Tolerance Test up to 2 years	3, 12 and 24 months	To investigate the influence of endovascular denervation on Oral Glucose Tolerance Test (OGTT).
Changes in catecholamine up to 2 years	3, 6, 12 and 24 months	To investigate the influence of endovascular denervation on catecholamine.
Changes in creatinine up to 2 years	3, 6, 12 and 24 months	To investigate the influence of endovascular denervation on creatinine.
Changes in insulin up to 2 years	3, 6, 12 and 24 months	To investigate the influence of endovascular denervation on insulin.
Changes in glucagon up to 2 years	3, 6, 12 and 24 months	To investigate the influence of endovascular denervation on glucagon.
Changes in blood pressure up to 2 years	3, 6, 12 and 24 months	To investigate the influence of endovascular denervation on blood pressure.
Changes in blood urea nitrogen (BUN) up to 2 years	3, 6, 12 and 24 months	To investigate the influence of endovascular denervation on BUN.

Trial Locations

Locations (1)

Zhongda Hospital, Southeast University; 🇨🇳 Nanjing, Jiangsu, China