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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
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.
University Hospital of North Norway
Tromsø, Norway
Change in blood pressure
Change in blood pressure from baseline to six months after the intervention
Time frame: from baseline to six months
Change in blood pressure
Change in blood pressure from baseline to two years after the intervention
Time frame: from baseline to two years
Change in quality of Life
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.
Time frame: From baseline to six months
Changes in glucose production and insulin sensitivity
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).
Time frame: from baseline to six months
Change in quality of Life
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.
Time frame: From baseline to two years
Changes in glucose production and insulin sensitivity
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).
Time frame: from baseline to two years
Effect of RDN on subclinical organ injury: Myocardium
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.
Time frame: from baseline to six months
Effect of RDN on subclinical organ injury: Myocardium
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.
Time frame: from baseline to two years
Effect of RDN on subclinical organ injury: Retinal vessels
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).
Time frame: from baseline to six months
Effect of RDN on subclinical organ injury: Retinal vessels
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).
Time frame: from baseline to two years
Effect of RDN on subclinical organ injury: Kidneys
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.
Time frame: from baseline to six months
Effect of RDN on subclinical organ injury: Kidneys
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.
Time frame: from baseline to two years
Effect of RDN on subclinical organ injury: Endothelial function
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.
Time frame: from baseline to six months
Effect of RDN on subclinical organ injury: Endothelial function
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.
Time frame: from baseline to two years
Effect of RDN on subclinical organ injury: Impedance cardiography
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)
Time frame: from baseline to two years
Effect of RDN on subclinical organ injury: Impedance cardiography
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)
Time frame: from baseline to six months
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