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Renal Denervation in Treatment Resistant Hypertension

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by University of Erlangen-Nürnberg Medical School
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT01687725
First received: September 13, 2012
Last updated: April 16, 2013
Last verified: April 2013
  Purpose

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 Intervention
Hypertension
Device: Renal denervation using Symplicity Catheter system

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Renal Denervation in Treatment Resistant Hypertension

Resource links provided by NLM:


Further study details as provided by University of Erlangen-Nürnberg Medical School:

Primary Outcome Measures:
  • office BP [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    change in office blood pressure from baseline to 6 months post-renal denervation

  • 24-ABPM [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    • 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 ] [ Designated as safety issue: No ]
    change in urinary albumin/creatinine ratio from baseline to 6 months post-renal denervation

  • Systemic RAS activity [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    • 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 ] [ Designated as safety issue: No ]
    • 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 ] [ Designated as safety issue: No ]
    change in urinary angiotensinogen concentration from the morning spot urine from baseline to 6 months post-renal denervation


Secondary Outcome Measures:
  • BP [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]
    • 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 ] [ Designated as safety issue: No ]
    • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    • 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 ] [ Designated as safety issue: No ]
    - 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 ] [ Designated as safety issue: No ]
    • 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


Estimated Enrollment: 100
Study Start Date: November 2010
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01687725

Contacts
Contact: Christian Ott, MD 0049-9131-85 ext 36245 christian.ott@uk-erlangen.de

Locations
Germany
Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg Recruiting
Erlangen, Germany, 91054
Contact: Christian Ott, MD    +49-9131-85 ext 36245    christian.ott@uk-erlangen.de   
Contact: Roland E Schmieder, MD    +49-9131-85 ext 36245    roland.schmieder@uk-erlangen.de   
Sub-Investigator: Christian Ott, MD         
Klinik für Innere Medizin, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes Recruiting
Homburg/Saar, Germany, 66421
Contact: Felix Mahfoud, MD    +496841-16 ext 21346    Felix.Mahfoud@uks.eu   
Contact: Michael Böhm, MD    +496841-16 ext 21346    michael.boehm@uks.eu   
Sub-Investigator: Felix Mahfoud, MD         
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Investigators
Principal Investigator: Roland E Schmieder, MD University of Erlangen-Nürnberg
  More Information

No publications provided by University of Erlangen-Nürnberg Medical School

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT01687725     History of Changes
Other Study ID Numbers: RD-TRH
Study First Received: September 13, 2012
Last Updated: April 16, 2013
Health Authority: Germany: Ethics Commission

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014