Renal Denervation in Treatment Resistant Hypertension

NCT01687725 | Completed

• 1 other identifier: RD-TRH
• Study Type: observational
• Target: 41
• Locations: 1 country
• Sites: 2

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

Conditions

Hypertension

Outcome Measures

Primary Outcomes (7)

• office BP

  change in office blood pressure from baseline to 6 months post-renal denervation

  baseline, 6 months

• 24-ABPM

  change in 24 hour ambulatory blood pressure (ABPM) from baseline to 6 months post-renal denervation

  baseline, 6 months

• Magnetic resonance imaging (MRI)

  * 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

  baseline, 3 and 6 months

• Albuminuria

  change in urinary albumin/creatinine ratio from baseline to 6 months post-renal denervation

  baseline, 6 months

• Systemic RAS activity

  * 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

  baseline, 6 months

• Vascular structure and function of large and small arteries

  * 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

  baseline, 6 months

• Local RAS activity

  change in urinary angiotensinogen concentration from the morning spot urine from baseline to 6 months post-renal denervation

  baseline, 6 months

Secondary Outcomes (6)

• BP

  3 and 12 months

• MRI

  1 day and 12 months

• Local RAS activity

  1 day, 3 and 12 months

• Systemic RAS activity

  1 day, 3 and 12 months

• Albuminuria

  3 and 12 months

Study Arms (1)

Renal denervation

Renal denervation using Symplicity Catheter system

Device: Renal denervation using Symplicity Catheter system

Interventions

Renal denervation using Symplicity Catheter system DEVICE

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

Renal denervation

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

treatment resistant hypertensive adults

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (2)

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

Erlangen, 91054, Germany

Location

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

Homburg/Saar, 66421, Germany

Location

Related Publications (10)

• 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.

  PMID: 25916737 BACKGROUND

• 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.

  PMID: 27607458 BACKGROUND

• 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.

  PMID: 25923731 BACKGROUND

• Guenes-Altan M, Schmid A, Kannenkeril D, Linz P, Ott C, Bosch A, Schiffer M, Uder M, Schmieder RE. Skin sodium content as a predictor of blood pressure response to renal denervation. Hypertens Res. 2024 Feb;47(2):361-371. doi: 10.1038/s41440-023-01450-4. Epub 2023 Oct 25.

  PMID: 37880499 DERIVED

• 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.

  PMID: 31555795 DERIVED

• 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.

  PMID: 28845508 DERIVED

• 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.

  PMID: 26873693 DERIVED

• 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.

  PMID: 25982653 DERIVED

• 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.

  PMID: 24681017 DERIVED

• 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.

  PMID: 23850901 DERIVED

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Roland E Schmieder, MD

  University of Erlangen-Nürnberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: September 19, 2012
• Study Start: November 1, 2010
• Primary Completion: June 1, 2018
• Study Completion: December 1, 2018
• Last Updated: February 18, 2020

Record last verified: 2020-02

Locations

DE (2)