Renal Denervation in Treatment Resistant Hypertension

• ClinicalTrials.gov Identifier: NCT01687725
• Recruitment Status: Completed
• First Posted: September 19, 2012
• Last Update Posted: February 18, 2020
• Sponsor: University of Erlangen-Nürnberg Medical School
• Information provided by (Responsible Party): University of Erlangen-Nürnberg Medical School

Study Description

Brief Summary:

In patients with treatment resistant hypertension renal nerve ablation emerged as an effective interventional approach of treating hypertensive disease with a progressively increasing fall in blood pressure. Decreased activity of the sympathetic nervous system is one of the major underlying pathogenetic mechanism of the fall in blood pressure but the precise mechanisms that causes the fall in blood pressure in the short-term and, in particular, long-term remains elusive. The objective of the study is to understand the pathogenetic mechanisms of renal denervation beyond the reduced activity of the sympathetic nervous system. In 100 hypertensive patients most advanced technology will be applied, before and repeatedly after renal denervation, throughout the follow-up period of 1 year. Systemic activity of the renin angiotensin aldosterone system, renal perfusion (by MRI spin labeling technique), local activity of the renin angiotensin system in the kidney (urinary angiotensinogen concentrations), sodium excretion and total sodium content (23 Na-MRI technique) and vascular remodelling of small (retinal arterioles 50 - 150 µm) and large arteries (carotid - femoral pulse wave velocity and augmentation index, both measured over 24 hours) will be assessed. Identification of the pathogenetic mechanisms involved in the fall in blood pressure after renal denervation may help to identify those hypertensive patients that profit most from renal nerve ablation in terms of blood pressure reduction.

The investigators propose the following hypotheses why a progressive decrease in blood pressure happens, in addition to the decreased activity of the central nervous system, after renal nerve ablation:

Short term effects:

A)Preservation of renal function and perfusion B)Reduction of local RAS activity in the kidney C)Exaggerated sodium excretion immediately after renal nerve ablation

Long term effects:

D)Decrease of total sodium content after 6 and 12 months E)Improvement of vascular wall properties after 6 and 12 months

Condition or disease	Intervention/treatment
Hypertension	Device: Renal denervation using Symplicity Catheter system

Study Design

• Study Type: Observational
• Actual Enrollment: 41 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Renal Denervation in Treatment Resistant Hypertension
• Actual Study Start Date: November 2010
• Actual Primary Completion Date: June 2018
• Actual Study Completion Date: December 2018

Groups and Cohorts

Group/Cohort	Intervention/treatment
Renal denervation; Renal denervation using Symplicity Catheter system	Device: Renal denervation using Symplicity Catheter system; percutaneous selective renal sympathetic nerve ablation with the use of the Symplicity Catheter system

Outcome Measures

Primary Outcome Measures :

1. office BP [ Time Frame: baseline, 6 months ]
   change in office blood pressure from baseline to 6 months post-renal denervation
2. 24-ABPM [ Time Frame: baseline, 6 months ]
   change in 24 hour ambulatory blood pressure (ABPM) from baseline to 6 months post-renal denervation
3. Magnetic resonance imaging (MRI) [ Time Frame: baseline, 3 and 6 months ]
   • change in total sodium content measured by MRI from baseline to 6 months post-renal denervation
   • change in renal perfusion measured by MRI from baseline to 3 months post-renal denervation
4. Albuminuria [ Time Frame: baseline, 6 months ]
   change in urinary albumin/creatinine ratio from baseline to 6 months post-renal denervation
5. Systemic RAS activity [ Time Frame: baseline, 6 months ]
   • change in sodium, potassium and creatinine from baseline to 6 months post-renal denervation
   • change in aldosterone excretion from baseline to 6 months post-renal denervation
   • change in sodium/potassium ratio from baseline to 6 months post-renal denervation
   • change in plasma renin activity and angiotensin II concentration at least 30 minutes of rest in a supine position and immediately after standing from baseline to 6 months post-renal denervation
6. Vascular structure and function of large and small arteries [ Time Frame: baseline, 6 months ]
   • change in flow-mediated vasodilation (FMD)from baseline to 6 months post-renal denervation
   • change in scanning laser Doppler flowmetry (SLDF) from baseline to 6 months post-renal denervation
   • change in funduscopy from baseline to 6 months post-renal denervation
   • change in pulse wave analysis (PWA) from baseline to 6 months post-renal denervation
   • change in pulse wave velocity (PWV) from baseline to 6 months post-renal denervation
   • change in urinary albumine/creatinine ratio (UACR) of the morning spot urine sample from baseline to 6 months post-renal denervation
7. Local RAS activity [ Time Frame: baseline, 6 months ]
   change in urinary angiotensinogen concentration from the morning spot urine from baseline to 6 months post-renal denervation

Secondary Outcome Measures :

1. BP [ Time Frame: 3 and 12 months ]
   • change in office BP from baseline to 3 and 12 months post-renal denervation
   • change in 24 hour ABPM from baseline to 3 and 12 months post-renal denervation
2. MRI [ Time Frame: 1 day and 12 months ]
   • change in total sodium content measured by MRI from baseline to 12 months post-renal denervation
   • change in renal perfusion measured by MRI spin labelling technique from baseline to 1 day post-renal denervation
3. Local RAS activity [ Time Frame: 1 day, 3 and 12 months ]
   change urinary angiotensinogen concentration from the morning spot urine from baseline to 1 day, 3 and 12 months post-renal denervation
4. Systemic RAS activity [ Time Frame: 1 day, 3 and 12 months ]
   • change in sodium potassium and creatinine from baseline to 1 day, 3 and 12 months post-renal denervation
   • change in aldosterone excretion from baseline to 1 day, 3 and 12 months post-renal denervation
   • change in sodium/potassium ratio from baseline to 1 day, 3 and 12 months post-renal denervation
   • change in plasma renin activity and angiotensin II concentration at least 30 minutes of rest in a supine position and immediately after standing from baseline to 1 day, 3 and 12 months post-renal denervation
5. Albuminuria [ Time Frame: 3 and 12 months ]
   - change in albuminuria from baseline to 3 and 12 months post-renal denervation
6. Vascular structure and function of large and small arteries [ Time Frame: 3 and 12 months ]
   • change in flow mediated vasodilation (FMD) from baseline to 12 months post-renal denervation
   • change in scanning laser Doppler flowmetry (SLDF) from baseline to 12 months post-renal denervation
   • change in funduscopy from baseline to 3 and 12 months post-renal denervation
   • change in pulse wave analysis (PWA) from baseline to 12 months post-renal denervation
   • change in pulse wave velocity (PWV) from baseline to 12 months post-renal denervation
   • change in urinary albumine/creatinine ratio of the morning spot urine sample from baseline to 3 and 12 months post-renal denervation

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

treatment resistant hypertensive adults

Criteria

Inclusion Criteria:

• treatment resistant hypertension
• male of female aged over 18 years
• written informed consent
• agreement to attend all study visits as planned in the protocol

Exclusion Criteria:

• chronic kidney disease 3 - 5
• any contradictions for MRI
• claustrophobia
• strabismus
• severe ocular diseases
• history of epilepsia

Contacts and Locations

Locations

Germany

Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg

Erlangen, Germany, 91054

Klinik für Innere Medizin, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes

Homburg/Saar, Germany, 66421

Sponsors and Collaborators

University of Erlangen-Nürnberg Medical School

Investigators

• Principal Investigator: Roland E Schmieder, MD; University of Erlangen-Nürnberg

More Information

Publications:

Ott C, Harazny JM, Schmid A, Ditting T, Veelken R, Bladowski M, Michelson G, Uder M, Schmieder RE. Retinal microperfusion after renal denervation in treatment-resistant hypertensive patients. Clin Res Cardiol. 2015 Sep;104(9):782-9. doi: 10.1007/s00392-015-0845-0. Epub 2015 Apr 28.

Ott C, Mahfoud F, Schmid A, Ewen S, Toennes SW, Meyer MR, Helfer AG, Maurer HH, Ditting T, Veelken R, Zivanovic I, Uder M, Bohm M, Schmieder RE. The effect of renal denervation in moderate treatment-resistant hypertension with confirmed medication adherence. J Hypertens. 2016 Dec;34(12):2475-2479. doi: 10.1097/HJH.0000000000001110.

Ott C, Mahfoud F, Schmid A, Toennes SW, Ewen S, Ditting T, Veelken R, Ukena C, Uder M, Bohm M, Schmieder RE. Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension. J Hypertens. 2015 Jun;33(6):1261-6. doi: 10.1097/HJH.0000000000000556.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bosch A, Schmid A, Ott C, Kannenkeril D, Karg MV, Ditting T, Veelken R, Uder M, Schmieder RE. Copeptin Levels in Patients With Treatment-Resistant Hypertension Before and 6 Months After Renal Denervation. Am J Hypertens. 2020 Feb 22;33(2):182-189. doi: 10.1093/ajh/hpz155.

Ott C, Kopp C, Dahlmann A, Schmid A, Linz P, Cavallaro A, Hammon M, Ditting T, Veelken R, Uder M, Titze J, Schmieder RE. Impact of renal denervation on tissue Na+ content in treatment-resistant hypertension. Clin Res Cardiol. 2018 Jan;107(1):42-48. doi: 10.1007/s00392-017-1156-4. Epub 2017 Aug 28.

Schmieder RE, Ott C, Schmid A, Friedrich S, Kistner I, Ditting T, Veelken R, Uder M, Toennes SW. Adherence to Antihypertensive Medication in Treatment-Resistant Hypertension Undergoing Renal Denervation. J Am Heart Assoc. 2016 Feb 12;5(2):e002343. doi: 10.1161/JAHA.115.002343.

Ott C, Schmid A, Toennes SW, Ditting T, Veelken R, Uder M, Schmieder RE. Central pulse pressure predicts BP reduction after renal denervation in patients with treatment-resistant hypertension. EuroIntervention. 2015 May;11(1):110-6. doi: 10.4244/EIJV11I1A19.

Ott C, Mahfoud F, Schmid A, Ditting T, Veelken R, Ewen S, Ukena C, Uder M, Bohm M, Schmieder RE. Improvement of albuminuria after renal denervation. Int J Cardiol. 2014 May 1;173(2):311-5. doi: 10.1016/j.ijcard.2014.03.017. Epub 2014 Mar 15.

Ott C, Mahfoud F, Schmid A, Ditting T, Sobotka PA, Veelken R, Spies A, Ukena C, Laufs U, Uder M, Bohm M, Schmieder RE. Renal denervation in moderate treatment-resistant hypertension. J Am Coll Cardiol. 2013 Nov 12;62(20):1880-6. doi: 10.1016/j.jacc.2013.06.023. Epub 2013 Jul 10.

• Responsible Party: University of Erlangen-Nürnberg Medical School
• ClinicalTrials.gov Identifier: NCT01687725
• Other Study ID Numbers: RD-TRH
• First Posted: September 19, 2012
• Last Update Posted: February 18, 2020
• Last Verified: February 2020

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases