Renal Sympathetic Denervation and Potential Effects on Glucose Metabolism and Cardiovascular Risk-Factors
- Conditions
- Hypertension, Resistant to Conventional Therapy
- Interventions
- Procedure: Renal sympathetic denervation
- Registration Number
- NCT01630928
- Lead Sponsor
- University Hospital of North Norway
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Renal sympathetic denervation Renal sympathetic denervation Patients with treatment resistant hypertension
- Primary Outcome Measures
Name Time Method Change in blood pressure from baseline to two years Change in blood pressure from baseline to two years after the intervention
- Secondary Outcome Measures
Name Time Method Change in quality of Life 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.
Effect of RDN on subclinical organ injury: Myocardium 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.Changes in glucose production and insulin sensitivity 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).
Effect of RDN on subclinical organ injury: Endothelial function 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.Effect of RDN on subclinical organ injury: Impedance cardiography 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)
Effect of RDN on subclinical organ injury: Retinal vessels 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).Effect of RDN on subclinical organ injury: Kidneys 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.
Trial Locations
- Locations (1)
University Hospital of North Norway
🇳🇴Tromsø, Norway