Effect of Renal Denervation on NO-mediated Sodium Excretion and Plasma Levels of Vasoactive Hormones

Study Overview
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Brief Summary
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Catheter based renal denervation (CRD) in humans represents a promising new treatment of resistant hypertension. CRD is currently investigated as a treatment option in patients with resistant hypertension defined as at least 3 antihypertensive drugs (including a diuretic) in a randomized, sham-controlled, multicenter trial in Denmark (ReSet). In ReSet, patients are randomized to either CRD or a sham procedure with 6 months follow up. The mechanisms by which CRD reduce blood pressure are only partly understood and the interaction between renal sympathetic nerves and nitric oxide (NO) has not been investigated in humans. To Study the interaction between NO and renal sympathetic nerves, we designed the present substudy, where the effects of NO-inhibition on renal, hemodynamic and hormonal variables are studied before and after CRD.

Official Title
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Effect of Renal Denervation on NO-mediated Regulation of Salt- and Water Excretion, Vasoactive Hormones and Tubular Transport Proteins in Patients With Resistant Hypertension

Conditions
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Essential Hypertension

Intervention / Treatment
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* Drug: NG-monomethyl-L-arginine (L-NMMA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 30-70 years Stable antihypertensive treatment for 1-month with at least 3 antihypertensive drugs including a diuretic Day-time ambulatory blood pressure > 145/75 mmHg Exclusion Criteria: Non compliance Pregnancy/no-anticonception in fertile women Radiocontrast allergy Malignancy Congestive heart failure (EF < 50) eGFR < 45 Unstable angina pectoris Recent myocardial infarction or PCI (< 6 mdr) Secondary hypertension Renal artery stenosis or multiple renal arteries on CT Claudication

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Renal denervation<br>Patient group randomized to renal denervation | Drug: NG-monomethyl-L-arginine (L-NMMA)<br>* Acute L-NMMA treatment (4,5 mg/kg loading dose followed by 3 mg/kg sustain infusion for 1 hour)<br>|
| Sham Comparator: Sham<br>Patients randomized to sham procedure | Drug: NG-monomethyl-L-arginine (L-NMMA)<br>* Acute L-NMMA treatment (4,5 mg/kg loading dose followed by 3 mg/kg sustain infusion for 1 hour)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional excretion of sodium after acute L-NMMA treatment |  | 1 month before and after CRD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular filtration rate (GFR) before and after L-NMMA treatment |  | 1 month before and after CRD | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal denervation, Sodium, GFR, Essential hypertension, Nitric oxide