Renal Sympathetic Denervation and Potential Effects on Glucose Metabolism and Cardiovascular Risk-Factors (Re-Shape)

May 13, 2016 updated by: University Hospital of North Norway

Renal Sympathetic Denervation for Treatment Resistant Hypertension and Potential Effects on Glucose Metabolism and Cardiovascular Risk-Factors (The Re-Shape CV-Risk Study)

The Re-Shape CV-Risk Study is a clinical study where renal adrenergic denervation (RDN) is done in high risk patients with treatment-resistant hypertension. RDN is a mini-invasive, percutaneous technique where an ablation catheter is inserted through a femoral artery into the renal arteries, for destruction of the adrenergic nerve bundles in the artery adventitia by means of radio-frequency ablation. RDN leads to sympathetic denervation of the kidneys, which in the "Symplicity trials" led to an impressive reduction of blood pressure (- 33 /-11 mmHg). In a pilot study, where 40 % of the patients had diabetes, RDN seemed to have beneficial effects not only on blood pressure, but also on insulin sensitivity and hyperinsulinaemia.

The investigators aim to introduce RDN as a clinical study where blood pressure reduction and methodical, technical aspects will be evaluated, but more importantly, also additional effects of RDN on sub-clinical organ damage (endothelial function, vascular stiffness, fundus-, heart-, kidney injury), quality of life, arrhythmia, and glucose metabolism. The investigators hypothesis is that RDN will have positive effect on glucose metabolism, QOL and sub-clinical organ damage.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Tromsø, Norway, N-9038
        • University Hospital of North Norway

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥ 18 Years.
  • Resistant hypertension, as defined in the 2007 ESH-ESC guidelines and confirmed by ambulatory or home blood pressure measurements. (Here office BP > 140/90 mmHg on 4 or more antihypertensive drugs in adequate dosages (including one diuretic) or certified drug intolerance).
  • No known secondary reason for hypertension
  • Negative pregnancy test (preferably blood hCG) for female patients of childbearing potential
  • Estimated GFR (glomerular filtration rate) > 45 mL/min/1.73m².
  • Willing and able to comply with follow-up requirements
  • Signed informed consent

Exclusion Criteria:

  • Type 1 and type 2 diabetes
  • Pregnancy
  • Allergy to the contrast medium used during RDN and Iohexol clearance.
  • Age > 68 years
  • Hemodynamically significant heart valve disease
  • Pacemaker or ICD
  • Medication that may interfere with the procedure (Anticoagulation, Platelet inhibitors, Steroids), if they cannot be temporarily reduced or stopped.
  • Cancer
  • Patients with transplanted kidneys
  • Reno vascular conditions like diameter < 4mm, renal artery stenosis or significant atherosclerosis, previous renal artery stenting

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Renal sympathetic denervation
Patients with treatment resistant hypertension
Procedure: Renal sympathetic denervation
This is a mini-invasive trans-catheter procedure with access via a 6F introducer in one of the femoral arteries. The renal sympathetic nerves arise from T10-L2, arborize around the renal artery and primarily lie within the adventitia. A specialized radiofrequency (RF) ablation catheter is introduced into the renal arteries, first one side, then on the other. Usually, 4-6 two-minute treatments per artery using a proprietary RF generator with automated low power and built-in safety algorithms are sufficient to ablate the sympathetic afferent and efferent fibers.
Other Names:
  • Symplicity Catheter (Medtronic)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in blood pressure
Time Frame: from baseline to six months
Change in blood pressure from baseline to six months after the intervention
from baseline to six months
Change in blood pressure
Time Frame: from baseline to two years
Change in blood pressure from baseline to two years after the intervention
from baseline to two years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in quality of Life
Time Frame: From baseline to six months
The international questionnaires SF-36 and 15-D, with some additional specific questions previously used in international studies will be used for evaluation of RDN effect on symptoms and QOL.
From baseline to six months
Changes in glucose production and insulin sensitivity
Time Frame: from baseline to six months
Glucose metabolism will be assessed with oral glucose tolerance test and 2-step euglycemic, hyperinsulinaemic clamp with tracer technique (6,6-2H2-glucose + HOTGINF / measurement of tracer-to-tracee ratio with mass spectrometry): Assessment of endogenous glucose production at fasting condition, at insulin levels around 30 mU/ml (hepatic insulin sensitivity), and at insulin levels of 65-68 mU/ml, imitating the postprandial state (peripheral insulin resistance). Assessment of glucose uptake at these conditions (insulin sensitivity).
from baseline to six months
Change in quality of Life
Time Frame: From baseline to two years
The international questionnaires SF-36 and 15-D, with some additional specific questions previously used in international studies will be used for evaluation of RDN effect on symptoms and QOL.
From baseline to two years
Changes in glucose production and insulin sensitivity
Time Frame: from baseline to two years
Glucose metabolism will be assessed with oral glucose tolerance test and 2-step euglycemic, hyperinsulinaemic clamp with tracer technique (6,6-2H2-glucose + HOTGINF / measurement of tracer-to-tracee ratio with mass spectrometry): Assessment of endogenous glucose production at fasting condition, at insulin levels around 30 mU/ml (hepatic insulin sensitivity), and at insulin levels of 65-68 mU/ml, imitating the postprandial state (peripheral insulin resistance). Assessment of glucose uptake at these conditions (insulin sensitivity).
from baseline to two years
Effect of RDN on subclinical organ injury: Myocardium
Time Frame: from baseline to six months

Long standing hypertension leads to sub-clinical organ damage:

Myocardial and vascular remodeling measured with echo cardiography. Wall stiffness, left ventricular function, hypertrophy and mass.
from baseline to six months
Effect of RDN on subclinical organ injury: Myocardium
Time Frame: from baseline to two years

Long standing hypertension leads to sub-clinical organ damage:

Myocardial and vascular remodeling measured with echo cardiography. Wall stiffness, left ventricular function, hypertrophy and mass.
from baseline to two years
Effect of RDN on subclinical organ injury: Retinal vessels
Time Frame: from baseline to six months

Long standing hypertension leads to sub-clinical organ damage:

Changes in the microcirculatory vasculature detectable as early changes in retinal vascular caliber or presence of hypertensive retinopathy. High resolution photography (Carl Zeiss Meditec.) and optic coherence tomography of the retina give a direct view to microcirculation. Analyzes will be performed using computer assisted morphometry (IVAN/Retinal Analysis software. Fundus Reading center, University of Wisconsin, Madison USA).
from baseline to six months
Effect of RDN on subclinical organ injury: Retinal vessels
Time Frame: from baseline to two years

Long standing hypertension leads to sub-clinical organ damage:

Changes in the microcirculatory vasculature detectable as early changes in retinal vascular caliber or presence of hypertensive retinopathy. High resolution photography (Carl Zeiss Meditec.) and optic coherence tomography of the retina give a direct view to microcirculation. Analyzes will be performed using computer assisted morphometry (IVAN/Retinal Analysis software. Fundus Reading center, University of Wisconsin, Madison USA).
from baseline to two years
Effect of RDN on subclinical organ injury: Kidneys
Time Frame: from baseline to six months

Long standing hypertension leads to sub-clinical organ damage:

Renal dysfunction. We will measure serum creatinine, cystatin C, GFR (iohexol clearance), albumine/creatinine ratio and N-Acetyl-ß-glucosaminidase (NAG) in morning urine (two different days) before and after RDN. NAG excretion is a sign of tubular injury.
from baseline to six months
Effect of RDN on subclinical organ injury: Kidneys
Time Frame: from baseline to two years

Long standing hypertension leads to sub-clinical organ damage:

Renal dysfunction. We will measure serum creatinine, cystatin C, GFR (iohexol clearance), albumine/creatinine ratio and N-Acetyl-ß-glucosaminidase (NAG) in morning urine (two different days) before and after RDN. NAG excretion is a sign of tubular injury.
from baseline to two years
Effect of RDN on subclinical organ injury: Endothelial function
Time Frame: from baseline to six months

Long standing hypertension leads to sub-clinical organ damage:

Impaired endothelial function; assessed with plethysmography under reactive hyperemia + markers of endothelial dysfunction; Peripheral vasodilator function is measured by digital pulse amplitude tonometry using EndoPAT 2000 (Itamar Medical Ltd., Caesarea, Israel). Reactive hyperemia is produced by applying a blood pressure cuff for 5 min at a pressure of 60 mmHg higher than the systolic pressure on the upper part of the arm.
from baseline to six months
Effect of RDN on subclinical organ injury: Endothelial function
Time Frame: from baseline to two years

Long standing hypertension leads to sub-clinical organ damage:

Impaired endothelial function; assessed with plethysmography under reactive hyperemia + markers of endothelial dysfunction; Peripheral vasodilator function is measured by digital pulse amplitude tonometry using EndoPAT 2000 (Itamar Medical Ltd., Caesarea, Israel). Reactive hyperemia is produced by applying a blood pressure cuff for 5 min at a pressure of 60 mmHg higher than the systolic pressure on the upper part of the arm.
from baseline to two years
Effect of RDN on subclinical organ injury: Impedance cardiography
Time Frame: from baseline to two years
Increased central blood pressure measured in ascending aorta, in addition to "augmentation index" (peak aortic pressure increase/pulse pressure) as a measure of vessel compliance, are independent predictors for hypertensive organ injury (brain, heart, kidneys). Aortic wall-stiffness (compliance) and pulse wave reflection are important determinants for central blood pressure and are among the parameters we indirectly will get from impedance cardiography (Hotman System, HEMO SAPIENS INC, Bucharest, Romania)
from baseline to two years
Effect of RDN on subclinical organ injury: Impedance cardiography
Time Frame: from baseline to six months
Increased central blood pressure measured in ascending aorta, in addition to "augmentation index" (peak aortic pressure increase/pulse pressure) as a measure of vessel compliance, are independent predictors for hypertensive organ injury (brain, heart, kidneys). Aortic wall-stiffness (compliance) and pulse wave reflection are important determinants for central blood pressure and are among the parameters we indirectly will get from impedance cardiography (Hotman System, HEMO SAPIENS INC, Bucharest, Romania)
from baseline to six months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital of North Norway

Collaborators

University of Tromso
The Royal Norwegian Ministry of Health
Odd Berg Medical research Foundation

Investigators

  • Principal Investigator: Terje K. Steigen, MD, PhD, Dept. of Cardiology, University Hospital of North Norway and University of Tromsø, Norway
  • Study Chair: Ingrid Toft, MD, PhD, Dept. of Nephrology, University Hospital of North Norway and University of Tromsø
  • Study Director: Marit D Solbu, MD, PhD, Dept of Nephrology, University Hospital of North Norway and University of Tromsø

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

June 26, 2012

First Submitted That Met QC Criteria

June 27, 2012

First Posted (Estimate)

June 28, 2012

Study Record Updates

Last Update Posted (Estimate)

May 16, 2016

Last Update Submitted That Met QC Criteria

May 13, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011/1296 (REK)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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