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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Tromso
The Royal Norwegian Ministry of Health
Odd Berg Medical research Foundation
Information provided by (Responsible Party):
University Hospital of North Norway
ClinicalTrials.gov Identifier:
NCT01630928
First received: June 26, 2012
Last updated: February 24, 2014
Last verified: March 2013
  Purpose

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.


Condition Intervention
Hypertension, Resistant to Conventional Therapy
Procedure: Renal sympathetic denervation

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Renal Sympathetic Denervation for Treatment Resistant Hypertension and Potential Effects on Glucose Metabolism and Cardiovascular Risk-Factors (The Re-Shape CV-Risk Study)

Resource links provided by NLM:


Further study details as provided by University Hospital of North Norway:

Primary Outcome Measures:
  • Change in blood pressure [ Time Frame: from baseline to six months ] [ Designated as safety issue: No ]
    Change in blood pressure from baseline to six months after the intervention

  • Change in blood pressure [ Time Frame: from baseline to two years ] [ Designated as safety issue: No ]
    Change in blood pressure from baseline to two years after the intervention


Secondary Outcome Measures:
  • Change in quality of Life [ Time Frame: From baseline to six months ] [ Designated as safety issue: No ]
    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.

  • Changes in glucose production and insulin sensitivity [ Time Frame: from baseline to six months ] [ Designated as safety issue: No ]
    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).

  • Change in quality of Life [ Time Frame: From baseline to two years ] [ Designated as safety issue: No ]
    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.

  • Changes in glucose production and insulin sensitivity [ Time Frame: from baseline to two years ] [ Designated as safety issue: No ]
    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).

  • Effect of RDN on subclinical organ injury: Myocardium [ Time Frame: from baseline to six months ] [ Designated as safety issue: No ]

    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.


  • Effect of RDN on subclinical organ injury: Myocardium [ Time Frame: from baseline to two years ] [ Designated as safety issue: No ]

    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.


  • Effect of RDN on subclinical organ injury: Retinal vessels [ Time Frame: from baseline to six months ] [ Designated as safety issue: No ]

    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).


  • Effect of RDN on subclinical organ injury: Retinal vessels [ Time Frame: from baseline to two years ] [ Designated as safety issue: No ]

    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).


  • Effect of RDN on subclinical organ injury: Kidneys [ Time Frame: from baseline to six months ] [ Designated as safety issue: No ]

    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.


  • Effect of RDN on subclinical organ injury: Kidneys [ Time Frame: from baseline to two years ] [ Designated as safety issue: No ]

    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.


  • Effect of RDN on subclinical organ injury: Endothelial function [ Time Frame: from baseline to six months ] [ Designated as safety issue: No ]

    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.


  • Effect of RDN on subclinical organ injury: Endothelial function [ Time Frame: from baseline to two years ] [ Designated as safety issue: No ]

    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.


  • Effect of RDN on subclinical organ injury: Impedance cardiography [ Time Frame: from baseline to two years ] [ Designated as safety issue: No ]
    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)

  • Effect of RDN on subclinical organ injury: Impedance cardiography [ Time Frame: from baseline to six months ] [ Designated as safety issue: No ]
    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)


Estimated Enrollment: 50
Study Start Date: March 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Symplicity Catheter (Medtronic)

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01630928

Locations
Norway
University Hospital of North Norway
Tromsø, Norway, N-9038
Sponsors and Collaborators
University Hospital of North Norway
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 Dahl Solbu, MD, PhD Dept of Nephrology, University Hospital of North Norway and University of Tromsø
  More Information

No publications provided

Responsible Party: University Hospital of North Norway
ClinicalTrials.gov Identifier: NCT01630928     History of Changes
Other Study ID Numbers: 2011/1296 (REK)
Study First Received: June 26, 2012
Last Updated: February 24, 2014
Health Authority: Norway:National Committee for Medical and Health Research Ethics
Norway: Data Protection Authority
Norway: Directorate of Health

Keywords provided by University Hospital of North Norway:
Renal denervation
Resistant Hypertension
Cardiovascular disease
Diabetes
Quality of LIfe

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 22, 2014