The Effect of Renal Denervation on Biological Variables

Objective: The objectives of this study are: the investigation of changes in left ventricular mass (LV mass) after RD using MRI, renal perfusion and renal oxygenation after RD using dynamic contrast enhanced MRI (DCE MRI)and blood oxygenation level dependent MRI (BOLD MRI), the evaluation of safety of RD, in terms of structural changes in the renal arteries and kidney using Magnetic resonance angiography (MRA). Secondly the evaluation of changes in various biological functions assessed by analysis of blood and/or urine samples. Thirdly the quantification of changes in blood pressure. Finally the changes in pulse wave velocity (PWV) and heart rate variability (HRV).

Study design: Observational exploratory-study.

Study population: Adults with a systolic BP ≥160 mmHg (≥150 mmHg for type 2 diabetics) with a stable drug regimen including 3 or more antihypertensive medications, including a diuretic, or inability to follow a stable drug regimen due to unacceptable side-effects of antihypertensive medication.

Main study parameters/endpoints: The effect of RD on: radiological variables: left ventricular wall mass, renal perfusion, renal oxygenation and the anatomy of the renal arteries. Secondly the effect of RD on biological variables assessed by analysis of blood and/or urine samples. Thirdly the changes in blood pressure. Finally the changes in PWV and HRV after RD.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risks associated with the tests and procedures performed for the clinical study are limited. There are no known risks associated with MRI when appropriate safety guidelines are followed. Based on the experience form our previous studies, we do not expect any potential risks regarding the cessation of anti-hypertensives.

Inclusion criteria

• Individual has a systolic BP ≥160 mmHg (≥150 mmHg for type 2 diabetics) based on an average of 3 office BP readings measured according to the guidelines in appendix A.
• Individual is adhering to a stable drug regimen including 3 or more antihypertensive medications, including a diuretic (with no changes for a minimum of 2 weeks prior to enrolment) which is expected to be maintained for at least 6 months. Or:
• Has experienced side effects to several anti-hypertensive medications
• Individual is ≥18 years of age.
• Individual agrees to have all study procedures performed, and is competent and willing to provide written, informed consent to participate in this clinical study.

Exclusion criteria

• Individual has a treatable secondary cause of hypertension. (it is possible that during baseline procedures secondary causes of hypertension are discovered, those individuals will be excluded from participation of the study.)
• Individual has renal artery anatomy that is ineligible for treatment including:
• Main renal arteries < 4 mm in diameter or < 20 mm in length.
• Hemodynamically or anatomically significant renal artery abnormality or stenosis in either renal artery which, in the eyes of the operator, would interfere with safe cannulation of the renal artery or meets standards for surgical repair or interventional dilation.
• A history of prior renal artery stenting.
• Multiple main renal arteries in either kidney.
• Individual has an estimated glomerular filtration rate (eGFR) of <30mL/min/1.73m2, using the MDRD calculation.
• Individual has type 1 diabetes mellitus.
• Individual has experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 6 months of the screening visit, or has widespread atherosclerosis, with documented intravascular thrombosis or unstable plaques.
• Individual has scheduled or planned surgery or cardiovascular intervention in the next 6 months.
• Individual has hemodynamically significant valvular heart disease for which reduction of BP would be considered hazardous.
• Individual has an implantable cardioverter defibrillator (ICD) or pacemaker whose settings cannot allow for RF energy delivery.
• Individual has any serious medical condition, which in the opinion of the investigator, may adversely affect the safety and/or effectiveness of the participant or the study (i.e., patients with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, haemophilia, or significant anaemia, or arrhythmias such as atrial fibrillation).
• Individual is pregnant, nursing or planning to be pregnant.
• Individual has a known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or would be unlikely or unable to comply with study follow-up requirements.
• Individual is currently enrolled in another investigational drug or device trial.
• Individual is currently being treated with any of the following medications:

• Drugs that cause salt retention (e.g., systemic corticosteroids and fludrocortisone)
• Warfarin or phenprocoumon that cannot be temporarily stopped for the procedure.
• Any contraindications for MRI:

• The presence of implanted cardiac pacemakers and/or auto-implanted cardioverter defibrillators.
• Mechanical cardiac valves.
• Implanted electronic devices like cochlear implants and nerve stimulators.
• Patients who are unable to fit into the bore of the magnet.
• Claustrophobia.
• Prosthesis of a joint.