The Effects of Renal Denervation on Insulin Sensitivity

Study Overview
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Brief Summary
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Renal sympathetic nerves contribute to development of hypertension. Sympathetic overactivity also induces insulin resistance and it could therefore be assumed that a renal denervation might improve insulin sensitivity. Studies have shown that glucose metabolism is improved in patients with treatment resistant essential hypertension both 1 and 3 months after renal denervation compared to a control group with treatment resistant essential hypertension. Fasting glucose, insulin and C-peptide decreased significantly as did insulin resistance assessed by HOMA-IR. The investigators wish to investigate the effect of renal denervation on insulin sensitivity using the gold standard - the hyperinsulinemic euglycemic clamp and to investigate the degree of insulin resistance in muscle, liver and adipose tissue.

Official Title
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The Effects of Renal Sympathetic Denervation on Insulin Sensitivity in Patients With Resistant Essential Hypertension

Conditions
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Treatment Resistant Essential Hypertension, Insulin Resistance

Intervention / Treatment
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* Procedure: Renal denervation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Systolic daytime ambulatory BP at least 145 mmHg and compliance to a minimum of 3 antihypertensive drugs, including a diuretic Exclusion Criteria: Diabetes Pregnancy Non compliance Heart Failure (NYHA 3-4) LV ejection fraction < 50 % Renal insufficiency (eGFR<30) Unstable coronary heart disease Coronary intervention within 6 months Myocardial infarction within 6 months Claudication Orthostatic syncope within 6 months Secondary Hypertension Permanent atrial fibrillation Significant Heart Valve Disease Clinically Significant abnormal electrolytes, haemoglobin, Liver enzymes, TSH Second and third degree heart block Macroscopic haematuria Proximal significant coronary stenosis Renal artery anatomy not suitable for renal artery ablation (Stenosis, small diameter < 4 mm, length < 2 cm, multiple renal arteries, severe calcifications)

Ages Eligible for Study
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Minimum Age: 30 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: Renal denervation<br>The patients will be examined prior to renal denervation and 6 months after. Thus the patients are their own controls. | Procedure: Renal denervation<br>* The patients are examined prior to and 6 months after renal denervation. On the day of examination the patients will have blood samples taken and the hyperinsulinemic euglycemic clamp and muscle and adipose tissue biopsies will be performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity expressed as an M-value | To assess insulin sensitivity the hyperinsulinemic euglycemic clamp is used. The patients are given 0.8 mU/kg/min insulin as an infusion for 2 hours and the blood glucose is clamped at 5 mmol/l. For assessment of endogenous glucose production (EGP) during the glucose clamps, a tracer (3-3 H glucose) is added to the glucose infusion. The patients will be examined by the hyperinsulinemic euglycemic clamp prior to the renal denervation and 6 months after. | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin signaling | Two biopsies from the lateral vastus muscle and two biopsies from the abdominal subcutaneous adipose tissue are obtained under local anesthesia. Biopsies are taken at baseline and during the clamp. Protein expression involved in the insulin signalling cascade is assessed using standard western blotting techniques. | 6 months |