The Effects of Renal Denervation on Insulin Sensitivity

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

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.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Treatment Resistant Essential Hypertension
• Intervention / Treatment: Procedure: Renal denervation

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Medical Research Laboratories, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Renal denervation; The patients will be examined prior to renal denervation and 6 months after. Thus the patients are their own controls.	Procedure: Renal denervation; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Per Løgstrup, MD Dr Sci, Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): March 30, 2015
• Study Completion (Actual): March 3, 2016

Study Registration Dates

• First Submitted: June 25, 2012
• First Submitted That Met QC Criteria: June 27, 2012
• First Posted (Estimate): June 29, 2012

Study Record Updates

• Last Update Posted (Actual): May 2, 2018
• Last Update Submitted That Met QC Criteria: May 1, 2018
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Hypertension; Insulin Resistance; Essential Hypertension
• Other Study ID Numbers: UKOM20110071