The MILESTONE Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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MultI-eLectrode EndovaScular denervaTiOn in patieNts With Type 2 Diabetes mEllitus (MILESTONE) Study

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Device: Endovascular Denervation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Endovascular Denervation<br> | Device: Endovascular Denervation<br>* multi-electrode catheter-based endovascular denervation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Oral Glucose Tolerance Test from baseline to 6 months | To investigate the influence of endovascular denervation on Oral Glucose Tolerance Test (OGTT). | 6 months | 
| Changes in glycosylated hemoglobin from baseline to 6 months | To investigate the influence of endovascular denervation on glycosylated hemoglobin (HbA1c). | 6 months | 

Secondary Outcome Measures

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