<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01687725</url>
  </required_header>
  <id_info>
    <org_study_id>RD-TRH</org_study_id>
    <nct_id>NCT01687725</nct_id>
  </id_info>
  <brief_title>Renal Denervation in Treatment Resistant Hypertension</brief_title>
  <official_title>Renal Denervation in Treatment Resistant Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Erlangen-Nürnberg Medical School</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Erlangen-Nürnberg Medical School</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In patients with treatment resistant hypertension renal nerve ablation emerged as an&#xD;
      effective interventional approach of treating hypertensive disease with a progressively&#xD;
      increasing fall in blood pressure. Decreased activity of the sympathetic nervous system is&#xD;
      one of the major underlying pathogenetic mechanism of the fall in blood pressure but the&#xD;
      precise mechanisms that causes the fall in blood pressure in the short-term and, in&#xD;
      particular, long-term remains elusive. The objective of the study is to understand the&#xD;
      pathogenetic mechanisms of renal denervation beyond the reduced activity of the sympathetic&#xD;
      nervous system. In 100 hypertensive patients most advanced technology will be applied, before&#xD;
      and repeatedly after renal denervation, throughout the follow-up period of 1 year. Systemic&#xD;
      activity of the renin angiotensin aldosterone system, renal perfusion (by MRI spin labeling&#xD;
      technique), local activity of the renin angiotensin system in the kidney (urinary&#xD;
      angiotensinogen concentrations), sodium excretion and total sodium content (23 Na-MRI&#xD;
      technique) and vascular remodelling of small (retinal arterioles 50 - 150 µm) and large&#xD;
      arteries (carotid - femoral pulse wave velocity and augmentation index, both measured over 24&#xD;
      hours) will be assessed. Identification of the pathogenetic mechanisms involved in the fall&#xD;
      in blood pressure after renal denervation may help to identify those hypertensive patients&#xD;
      that profit most from renal nerve ablation in terms of blood pressure reduction.&#xD;
&#xD;
      The investigators propose the following hypotheses why a progressive decrease in blood&#xD;
      pressure happens, in addition to the decreased activity of the central nervous system, after&#xD;
      renal nerve ablation:&#xD;
&#xD;
      Short term effects:&#xD;
&#xD;
      A)Preservation of renal function and perfusion B)Reduction of local RAS activity in the&#xD;
      kidney C)Exaggerated sodium excretion immediately after renal nerve ablation&#xD;
&#xD;
      Long term effects:&#xD;
&#xD;
      D)Decrease of total sodium content after 6 and 12 months E)Improvement of vascular wall&#xD;
      properties after 6 and 12 months&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2010</start_date>
  <completion_date type="Actual">December 2018</completion_date>
  <primary_completion_date type="Actual">June 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>office BP</measure>
    <time_frame>baseline, 6 months</time_frame>
    <description>change in office blood pressure from baseline to 6 months post-renal denervation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>24-ABPM</measure>
    <time_frame>baseline, 6 months</time_frame>
    <description>change in 24 hour ambulatory blood pressure (ABPM) from baseline to 6 months post-renal denervation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Magnetic resonance imaging (MRI)</measure>
    <time_frame>baseline, 3 and 6 months</time_frame>
    <description>change in total sodium content measured by MRI from baseline to 6 months post-renal denervation&#xD;
change in renal perfusion measured by MRI from baseline to 3 months post-renal denervation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Albuminuria</measure>
    <time_frame>baseline, 6 months</time_frame>
    <description>change in urinary albumin/creatinine ratio from baseline to 6 months post-renal denervation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Systemic RAS activity</measure>
    <time_frame>baseline, 6 months</time_frame>
    <description>change in sodium, potassium and creatinine from baseline to 6 months post-renal denervation&#xD;
change in aldosterone excretion from baseline to 6 months post-renal denervation&#xD;
change in sodium/potassium ratio from baseline to 6 months post-renal denervation&#xD;
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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vascular structure and function of large and small arteries</measure>
    <time_frame>baseline, 6 months</time_frame>
    <description>change in flow-mediated vasodilation (FMD)from baseline to 6 months post-renal denervation&#xD;
change in scanning laser Doppler flowmetry (SLDF) from baseline to 6 months post-renal denervation&#xD;
change in funduscopy from baseline to 6 months post-renal denervation&#xD;
change in pulse wave analysis (PWA) from baseline to 6 months post-renal denervation&#xD;
change in pulse wave velocity (PWV) from baseline to 6 months post-renal denervation&#xD;
change in urinary albumine/creatinine ratio (UACR) of the morning spot urine sample from baseline to 6 months post-renal denervation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Local RAS activity</measure>
    <time_frame>baseline, 6 months</time_frame>
    <description>change in urinary angiotensinogen concentration from the morning spot urine from baseline to 6 months post-renal denervation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>BP</measure>
    <time_frame>3 and 12 months</time_frame>
    <description>change in office BP from baseline to 3 and 12 months post-renal denervation&#xD;
change in 24 hour ABPM from baseline to 3 and 12 months post-renal denervation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRI</measure>
    <time_frame>1 day and 12 months</time_frame>
    <description>change in total sodium content measured by MRI from baseline to 12 months post-renal denervation&#xD;
change in renal perfusion measured by MRI spin labelling technique from baseline to 1 day post-renal denervation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local RAS activity</measure>
    <time_frame>1 day, 3 and 12 months</time_frame>
    <description>change urinary angiotensinogen concentration from the morning spot urine from baseline to 1 day, 3 and 12 months post-renal denervation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic RAS activity</measure>
    <time_frame>1 day, 3 and 12 months</time_frame>
    <description>change in sodium potassium and creatinine from baseline to 1 day, 3 and 12 months post-renal denervation&#xD;
change in aldosterone excretion from baseline to 1 day, 3 and 12 months post-renal denervation&#xD;
change in sodium/potassium ratio from baseline to 1 day, 3 and 12 months post-renal denervation&#xD;
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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Albuminuria</measure>
    <time_frame>3 and 12 months</time_frame>
    <description>- change in albuminuria from baseline to 3 and 12 months post-renal denervation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular structure and function of large and small arteries</measure>
    <time_frame>3 and 12 months</time_frame>
    <description>change in flow mediated vasodilation (FMD) from baseline to 12 months post-renal denervation&#xD;
change in scanning laser Doppler flowmetry (SLDF) from baseline to 12 months post-renal denervation&#xD;
change in funduscopy from baseline to 3 and 12 months post-renal denervation&#xD;
change in pulse wave analysis (PWA) from baseline to 12 months post-renal denervation&#xD;
change in pulse wave velocity (PWV) from baseline to 12 months post-renal denervation&#xD;
change in urinary albumine/creatinine ratio of the morning spot urine sample from baseline to 3 and 12 months post-renal denervation</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">41</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Renal denervation</arm_group_label>
    <description>Renal denervation using Symplicity Catheter system</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Renal denervation using Symplicity Catheter system</intervention_name>
    <description>percutaneous selective renal sympathetic nerve ablation with the use of the Symplicity Catheter system</description>
    <arm_group_label>Renal denervation</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        treatment resistant hypertensive adults&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  treatment resistant hypertension&#xD;
&#xD;
          -  male of female aged over 18 years&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
          -  agreement to attend all study visits as planned in the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  chronic kidney disease 3 - 5&#xD;
&#xD;
          -  any contradictions for MRI&#xD;
&#xD;
          -  claustrophobia&#xD;
&#xD;
          -  strabismus&#xD;
&#xD;
          -  severe ocular diseases&#xD;
&#xD;
          -  history of epilepsia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roland E Schmieder, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Erlangen-Nürnberg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik für Innere Medizin, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes</name>
      <address>
        <city>Homburg/Saar</city>
        <zip>66421</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>25916737</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>27607458</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25923731</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2012</study_first_posted>
  <last_update_submitted>February 17, 2020</last_update_submitted>
  <last_update_submitted_qc>February 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01687725
org study id: RD-TRH
nct id: NCT01687725
lead sponsor: 
has dmc: No
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
observational model: Cohort
time perspective: Prospective
measure: office BP
time frame: baseline, 6 months
description: change in office blood pressure from baseline to 6 months post-renal denervation
measure: 24-ABPM
time frame: baseline, 6 months
description: change in 24 hour ambulatory blood pressure (ABPM) from baseline to 6 months post-renal denervation
measure: Magnetic resonance imaging (MRI)
time frame: baseline, 3 and 6 months
description: 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
measure: Albuminuria
time frame: baseline, 6 months
description: change in urinary albumin/creatinine ratio from baseline to 6 months post-renal denervation
measure: Systemic RAS activity
time frame: baseline, 6 months
description: 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
measure: Vascular structure and function of large and small arteries
time frame: baseline, 6 months
description: 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
measure: Local RAS activity
time frame: baseline, 6 months
description: change in urinary angiotensinogen concentration from the morning spot urine from baseline to 6 months post-renal denervation
measure: BP
time frame: 3 and 12 months
description: 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
measure: MRI
time frame: 1 day and 12 months
description: 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
measure: Local RAS activity
time frame: 1 day, 3 and 12 months
description: change urinary angiotensinogen concentration from the morning spot urine from baseline to 1 day, 3 and 12 months post-renal denervation
measure: Systemic RAS activity
time frame: 1 day, 3 and 12 months
description: 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
measure: Albuminuria
time frame: 3 and 12 months
description: - change in albuminuria from baseline to 3 and 12 months post-renal denervation
measure: Vascular structure and function of large and small arteries
time frame: 3 and 12 months
description: 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
arm group label: Renal denervation
description: Renal denervation using Symplicity Catheter system
intervention type: Device
intervention name: Renal denervation using Symplicity Catheter system
description: percutaneous selective renal sympathetic nerve ablation with the use of the Symplicity Catheter system
arm group label: Renal denervation
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Roland E Schmieder, MD
role: Principal Investigator
affiliation: University of Erlangen-Nürnberg
facility: 
facility: 
country: Germany
citation: 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
citation: 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
citation: 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
responsible party type: Sponsor
mesh term: Hypertension