Renal Nerve Stimulation in Uncontrolled Hypertensive Patients Undergoing Renal Denervation

Study Overview
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Brief Summary
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Study design: Investigator initiated, single center The study is aimed 1) To investigate the blood pressure (BP) change to renal nerve stimulation(RNS), and subsequently perform a renal denervation(RDN) procedure 1) to verify the cutoff value (RNS-induced systolic BP change <20 mmHg in post-RDN patients) could be a useful clinical endpoint in RDN therapy, and test the hypothesis that intense RDN could improve the efficacy of RDN.

Detailed Description
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Hypertension has become a global public health concern and associated with considerable risk of cardiovascular, cerebrovascular and kidney diseases. Although pharmacological blood pressure (BP) control can reduce these risks, BP control rates remain suboptimal. Resistant hypertension affects 10% to 15% of patients with hypertension and adequate BP control is associated with better clinical outcome of resistant hypertension. Percutaneous renal denervation system (RDN) is designed to disrupt renal afferent and efferent sympathetic nerves to modulate central sympathetic outflow and renal physiology, achieving sustained BP reduction. Although the randomized, sham-controlled trial, SYMPLICITY HTN-3 in 2014, failed to prove the effectiveness of RDN in reducing BP compared to sham procedure, three carefully designed, randomized sham-controlled RDN trials (SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED, and RADIANCE-HTN SOLO), all of which showed similar and clinically meaningful BP reductions without serious adverse events. RDN, therefore, has been approved and well utilized in clinical practice to treat resistant hypertension. However,15-30% of the patients are non-responders. The reason for this is unknown. Experimental data show that renal nerve stimulation (RNS) may serve as a functional endpoint to assess completeness of the RDN procedure. Our preliminary observation study showed low RNS-induced SBP change in post-RDN patients were associated with better BP lowering response. Our study objectives are 1) to investigate the BP change to RNS, and subsequently perform a RDN procedure 1) to verify the cutoff value (RNS-induced systolic BP change <20mmHg in post-RDN patients) could be a useful clinical endpoint in RDN therapy. Hypotheses: We hypothesize that an RNS-induced SBP increase of <20 mmHg in bilateral proximal main renal arteries immediately after RDN was associated with significant BP reductions 6 months following RDN. RNS-induced SBP changes could predict RDN response and even guide RDN strategies Study design: Investigator initiated, single center, prospective study Patient population: 60 patients (20 - 80 years old) Patients with HTN. 1) 24-hour ambulatory blood pressure monitoring (ABPM) was >130 or DBP >80 mmHg Exclusion criteria: Unsuitable renal artery anatomy (main renal artery lumen diameter ≤3 mm or a total length <20 mm of the main arteries). Secondary hypertension, including hyperaldosteronism, pheochromocytoma, renal artery stenosis(>50% stenosis in one or both arteries) Pregnancy Intervention: RNS-guided RDN will be performed Group A (N=35): RNS-induced SBP increase of <20 mmHg in bilateral proximal main renal arteries immediately after RDN Group B(N=25): RNS-induced SBP increase of >20 mmHg in bilateral proximal main renal arteries immediately after RDN Then we will further divided Group B into Group C (N=8): observation group Group D(N=17): intensive intervention group (intensive -RDN again and the goal was post RNS-induced SBP change <20 mmHg) Primary end-points: The primary end points were the low RNS-induced systolic BP changes after RDN, was associated with the lower 24-hour SBP.

Official Title
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National Tawan University Hospital

Conditions
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Hypertension

Intervention / Treatment
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* Procedure: nerve stimulation guided renal denervation procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with hypertension (HTN), including 24-hour ambulatory blood pressure >130/ 80 mmHg Age 20-80 years Glomerular filtration rate >45 mL/min Exclusion Criteria: Unsuitable renal artery anatomy computed tomographic angiography (main renal artery lumen diameter ≤3 mm or a total length <20 mm of the main arteries). untreated secondary HTN, including hyperaldosteronism, pheochromocytoma, renal artery stenosis(>50% stenosis)

Ages Eligible for Study
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Minimum Age: 20 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: RNS checked RDN
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low RNS-induced SBP change group<br>25 patients with the RNS-induced systolic BP change <20mmHg immediately after RDN | Procedure: nerve stimulation guided renal denervation procedure<br>* RNS-in<br>* Other names: RNS-guided RDN;|
| Placebo Comparator: High RNS-induced SBP change group<br>8 patients with the RNS-induced systolic BP change >20mmHg immediately after RDN | Procedure: nerve stimulation guided renal denervation procedure<br>* RNS-in<br>* Other names: RNS-guided RDN;|
| Experimental: intensive RDN group<br>17 patients with the initial RNS-induced systolic BP change >20mmHg immediately after RDN, received intensive RDN therapy and let the second RNS-induced systolic BP change < 20mmHg | Procedure: nerve stimulation guided renal denervation procedure<br>* RNS-in<br>* Other names: RNS-guided RDN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| arterial blood pressure response | Main study parameter will be the arterial blood pressure response to RNS immediately after RDN. | during procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood pressure at 6 months | 24 hours Blood pressure at 6 months after the intervention | 6 months after the intervention | 
| blood pressure at 12 months | 24 hours Blood pressure at 12 months after the intervention | 12 months after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal nerve stimulation, renal nerve denervation, Sympathetic nerve activity