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

Tracking Information

• First Submitted Date: September 13, 2012
• First Posted Date: September 19, 2012
• Last Update Posted Date: February 18, 2020
• Actual Study Start Date: November 2010
• Actual Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 18, 2012)

• office BP [ Time Frame: baseline, 6 months ]
  change in office blood pressure from baseline to 6 months post-renal denervation
• 24-ABPM [ Time Frame: baseline, 6 months ]
  change in 24 hour ambulatory blood pressure (ABPM) from baseline to 6 months post-renal denervation
• 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
• Albuminuria [ Time Frame: baseline, 6 months ]
  change in urinary albumin/creatinine ratio from baseline to 6 months post-renal denervation
• 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
• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 18, 2012)

• 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
• 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
• 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
• 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
• Albuminuria [ Time Frame: 3 and 12 months ]
  - change in albuminuria from baseline to 3 and 12 months post-renal denervation
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Renal Denervation in Treatment Resistant Hypertension
• Official Title: Renal Denervation in Treatment Resistant Hypertension

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

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: treatment resistant hypertensive adults
• Condition: Hypertension

Intervention

Device: Renal denervation using Symplicity Catheter system

percutaneous selective renal sympathetic nerve ablation with the use of the Symplicity Catheter system

Study Groups/Cohorts

Renal denervation

Renal denervation using Symplicity Catheter system

Intervention: Device: Renal denervation using Symplicity Catheter system

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, Böhm 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.
• Ott C, Mahfoud F, Schmid A, Toennes SW, Ewen S, Ditting T, Veelken R, Ukena C, Uder M, Böhm 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.
• 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). pii: 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, Böhm 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, Böhm 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 17, 2020): 41
• Original Estimated Enrollment (submitted: September 18, 2012): 100
• Actual Study Completion Date: December 2018
• Actual Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01687725
• Other Study ID Numbers: RD-TRH
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Erlangen-Nürnberg Medical School
• Study Sponsor: University of Erlangen-Nürnberg Medical School
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Erlangen-Nürnberg Medical School
• Verification Date: February 2020