<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/NCT02258061</url>
  </required_header>
  <id_info>
    <org_study_id>H-3-2011-034</org_study_id>
    <nct_id>NCT02258061</nct_id>
  </id_info>
  <brief_title>Optimal Cardiac Resynchronization Therapy Pacing Rate</brief_title>
  <official_title>Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-ischemic Heart Failure Patients: a Randomized Crossover Pilot Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The optimal pacing rate during cardiac resynchronization therapy (CRT) is not known.&#xD;
      Investigators investigate the impact of changing basal pacing frequencies on autonomic nerve&#xD;
      function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a double-blinded randomized crossover pilot study testing two basal pacing rates:&#xD;
      DDD-60 versus DDD-80. Each patient is paced for 2 periods of 90 days with DDD-60 and DDD-80&#xD;
      in a randomly sequence.&#xD;
&#xD;
      Blood samples NT-proBNP plasma levels are analysed at baseline and at the end of each phase&#xD;
      using electrochemiluminescence-immunoassay. Patients rest for 15 minutes before the samples&#xD;
      are taken.&#xD;
&#xD;
      These result are monitored by supervisory group to ensure that increase of more than 15% than&#xD;
      baseline values result in termination of study.&#xD;
&#xD;
      Investigators conduct two distinct questionnaires (Minnesota Living with Heart Failure&#xD;
      (LIfHE) questionnaire and Medical Outcome Survey Short Form (SF-36)) A symptom limiting&#xD;
      bicycle (Ergoline, Baden-Württemberg, Germany) exercise test is performed to measure maximum&#xD;
      work capacity and oxygen consumption at each phase.&#xD;
&#xD;
      Recordings of resting muscle sympathetic nerve activity (MSNA) are sought in all patients at&#xD;
      both rates of pacing. All patients are studied on the same set-up in the semi-recumbent&#xD;
      position after 30 minutes of rest. Tungsten microelectrodes (Iowa Bioengineering) are&#xD;
      inserted into the common peroneal nerve just below the knee.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2011</start_date>
  <completion_date type="Actual">June 2013</completion_date>
  <primary_completion_date type="Actual">June 2013</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>N-terminal pro-brain natriuretic peptide</measure>
    <time_frame>3 months</time_frame>
    <description>Observing the change in N-terminal pro-brain natriuretic peptide in 15 patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Autonomic nerve function</measure>
    <time_frame>3 months</time_frame>
    <description>Autonomic nerve function by micro-neurography measured in bursts/min and bursts/cardiac cycle in 15 patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak oxygen consumption (pVO2)</measure>
    <time_frame>3 months</time_frame>
    <description>pVO2 measured by a symptom limiting bicycle exercise test in 15 patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-perceived quality of life</measure>
    <time_frame>3 months</time_frame>
    <description>Measured with the LIfHE and SF-36 questionnaires in 15 patients</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Cardiac Resynchronization Therapy</condition>
  <condition>Heart Failure</condition>
  <condition>Bi-ventricular Pacing</condition>
  <condition>Sympathetic Activity</condition>
  <condition>Quality of Life</condition>
  <arm_group>
    <arm_group_label>DDD-80 pacing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To investigate the impact of basal pacing rates of 80-bpm (DDD-80) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) and (iii) self-perceived quality of life (QoL).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DDD-60 pacing</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>To investigate the impact of basal pacing rates of 60-bpm (DDD-60) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) self-perceived quality of life (QoL).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>DDD-80</intervention_name>
    <description>Basal pacing rate set to 80-bpm. Note:Patients have already pacemaker implanted before this study.</description>
    <arm_group_label>DDD-80 pacing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>DDD-60</intervention_name>
    <description>Basal pacing rate set to 60-bpm. Note:Patients have already pacemaker implanted before this study.</description>
    <arm_group_label>DDD-60 pacing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis with idiopathic dilated cardiomyopathy&#xD;
&#xD;
          -  CRT device implanted (with initial indication in accordance with European guidelines)&#xD;
             at least 6 months prior to inclusion.&#xD;
&#xD;
          -  New York Heart Association functional (NYHA) class II-IV&#xD;
&#xD;
          -  Sinus rhythm,&#xD;
&#xD;
          -  Hemodynamically stable&#xD;
&#xD;
          -  Biventricular pacing &gt; 90% of the time&#xD;
&#xD;
          -  On optimal medical treatment for heart failure with no changes in medications during&#xD;
             the past 3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  NYHA I&#xD;
&#xD;
          -  unable to perform exercise test (e.g. chronic obstructive pulmonary disease, severe&#xD;
             arthritis)&#xD;
&#xD;
          -  cancer&#xD;
&#xD;
          -  plasma creatinine &gt; 200 micromole per litre&#xD;
&#xD;
          -  an admission for decompensated HF or acute coronary syndrome in the preceding 3&#xD;
             months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adam A Ghotbi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rigshospitalet, University hospital of Copenhagen</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>Kuniyoshi RR, Martinelli M, Negrao CE, Siqueira SF, Rondon MU, Trombetta IC, Kuniyoshi FH, Laterza MC, Nishioka SA, Costa R, Tamaki WT, Crevelari ES, Peixoto Gde L, Ramires JA, Kalil R. Effects of cardiac resynchronization therapy on muscle sympathetic nerve activity. Pacing Clin Electrophysiol. 2014 Jan;37(1):11-8. doi: 10.1111/pace.12254. Epub 2013 Aug 16.</citation>
    <PMID>23952584</PMID>
  </reference>
  <reference>
    <citation>Agostoni P, Corra U, Cattadori G, Veglia F, Battaia E, La Gioia R, Scardovi AB, Emdin M, Metra M, Sinagra G, Limongelli G, Raimondo R, Re F, Guazzi M, Belardinelli R, Parati G, Magri D, Fiorentini C, Cicoira M, Salvioni E, Giovannardi M, Mezzani A, Scrutinio D, Di Lenarda A, Mantegazza V, Ricci R, Apostolo A, Iorio A, Paolillo S, Palermo P, Contini M, Vassanelli C, Passino C, Piepoli MF; MECKI Score Research Group. Prognostic value of indeterminable anaerobic threshold in heart failure. Circ Heart Fail. 2013 Sep 1;6(5):977-87. doi: 10.1161/CIRCHEARTFAILURE.113.000471. Epub 2013 Jul 23.</citation>
    <PMID>23881847</PMID>
  </reference>
  <reference>
    <citation>Stockburger M, de Teresa E, Lamas G, Desaga M, Koenig C, Habedank D, Cobo E, Navarro X, Wiegand U. Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy. Europace. 2014 Jan;16(1):63-70. doi: 10.1093/europace/eut217. Epub 2013 Jul 16.</citation>
    <PMID>23861381</PMID>
  </reference>
  <reference>
    <citation>Brenyo A, Barsheshet A, Rao M, Huang DT, Zareba W, McNitt S, Hall WJ, Peterson DR, Solomon SD, Moss AJ, Goldenberg I. Brain natriuretic peptide and cardiac resynchronization therapy in patients with mildly symptomatic heart failure. Circ Heart Fail. 2013 Sep 1;6(5):998-1004. doi: 10.1161/CIRCHEARTFAILURE.112.000174. Epub 2013 Jun 25.</citation>
    <PMID>23801020</PMID>
  </reference>
  <reference>
    <citation>Shukla A, Curtis AB, Mehra MR, Albert NM, Gheorghiade M, Heywood JT, Liu Y, O'Connor CM, Reynolds D, Walsh MN, Yancy CW, Fonarow GC. Factors associated with improvement in utilization of cardiac resynchronization therapy in eligible heart failure patients: findings from IMPROVE HF. Pacing Clin Electrophysiol. 2013 Apr;36(4):433-43. doi: 10.1111/pace.12090. Epub 2013 Feb 4.</citation>
    <PMID>23380000</PMID>
  </reference>
  <reference>
    <citation>Martin DO, Day JD, Lai PY, Murphy AL, Nayak HM, Villareal RP, Weiner S, Kraus SM, Stolen KQ, Gold MR. Atrial support pacing in heart failure: results from the multicenter PEGASUS CRT trial. J Cardiovasc Electrophysiol. 2012 Dec;23(12):1317-25. doi: 10.1111/j.1540-8167.2012.02402.x. Epub 2012 Jul 25.</citation>
    <PMID>22830441</PMID>
  </reference>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <last_update_submitted>October 6, 2014</last_update_submitted>
  <last_update_submitted_qc>October 6, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 7, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Dr. Adam Ali Ghotbi</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</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/NCT02258061
org study id: H-3-2011-034
nct id: NCT02258061
lead sponsor: 
has dmc: Yes
The optimal pacing rate during cardiac resynchronization therapy (CRT) is not known.
      Investigators investigate the impact of changing basal pacing frequencies on autonomic nerve
      function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL).
This is a double-blinded randomized crossover pilot study testing two basal pacing rates:
      DDD-60 versus DDD-80. Each patient is paced for 2 periods of 90 days with DDD-60 and DDD-80
      in a randomly sequence.

      Blood samples NT-proBNP plasma levels are analysed at baseline and at the end of each phase
      using electrochemiluminescence-immunoassay. Patients rest for 15 minutes before the samples
      are taken.

      These result are monitored by supervisory group to ensure that increase of more than 15% than
      baseline values result in termination of study.

      Investigators conduct two distinct questionnaires (Minnesota Living with Heart Failure
      (LIfHE) questionnaire and Medical Outcome Survey Short Form (SF-36)) A symptom limiting
      bicycle (Ergoline, Baden-Württemberg, Germany) exercise test is performed to measure maximum
      work capacity and oxygen consumption at each phase.

      Recordings of resting muscle sympathetic nerve activity (MSNA) are sought in all patients at
      both rates of pacing. All patients are studied on the same set-up in the semi-recumbent
      position after 30 minutes of rest. Tungsten microelectrodes (Iowa Bioengineering) are
      inserted into the common peroneal nerve just below the knee.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: N-terminal pro-brain natriuretic peptide
time frame: 3 months
description: Observing the change in N-terminal pro-brain natriuretic peptide in 15 patients
measure: Autonomic nerve function
time frame: 3 months
description: Autonomic nerve function by micro-neurography measured in bursts/min and bursts/cardiac cycle in 15 patients
measure: Peak oxygen consumption (pVO2)
time frame: 3 months
description: pVO2 measured by a symptom limiting bicycle exercise test in 15 patients
measure: Self-perceived quality of life
time frame: 3 months
description: Measured with the LIfHE and SF-36 questionnaires in 15 patients
arm group label: DDD-80 pacing
arm group type: Experimental
description: To investigate the impact of basal pacing rates of 80-bpm (DDD-80) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) and (iii) self-perceived quality of life (QoL).
arm group label: DDD-60 pacing
arm group type: Sham Comparator
description: To investigate the impact of basal pacing rates of 60-bpm (DDD-60) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) self-perceived quality of life (QoL).
intervention type: Procedure
intervention name: DDD-80
description: Basal pacing rate set to 80-bpm. Note:Patients have already pacemaker implanted before this study.
arm group label: DDD-80 pacing
intervention type: Procedure
intervention name: DDD-60
description: Basal pacing rate set to 60-bpm. Note:Patients have already pacemaker implanted before this study.
arm group label: DDD-60 pacing
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adam A Ghotbi, MD
role: Principal Investigator
affiliation: Rigshospitalet, Denmark
facility: 
country: Denmark
citation: Kuniyoshi RR, Martinelli M, Negrao CE, Siqueira SF, Rondon MU, Trombetta IC, Kuniyoshi FH, Laterza MC, Nishioka SA, Costa R, Tamaki WT, Crevelari ES, Peixoto Gde L, Ramires JA, Kalil R. Effects of cardiac resynchronization therapy on muscle sympathetic nerve activity. Pacing Clin Electrophysiol. 2014 Jan;37(1):11-8. doi: 10.1111/pace.12254. Epub 2013 Aug 16.
PMID: 23952584
citation: Agostoni P, Corra U, Cattadori G, Veglia F, Battaia E, La Gioia R, Scardovi AB, Emdin M, Metra M, Sinagra G, Limongelli G, Raimondo R, Re F, Guazzi M, Belardinelli R, Parati G, Magri D, Fiorentini C, Cicoira M, Salvioni E, Giovannardi M, Mezzani A, Scrutinio D, Di Lenarda A, Mantegazza V, Ricci R, Apostolo A, Iorio A, Paolillo S, Palermo P, Contini M, Vassanelli C, Passino C, Piepoli MF; MECKI Score Research Group. Prognostic value of indeterminable anaerobic threshold in heart failure. Circ Heart Fail. 2013 Sep 1;6(5):977-87. doi: 10.1161/CIRCHEARTFAILURE.113.000471. Epub 2013 Jul 23.
PMID: 23881847
citation: Stockburger M, de Teresa E, Lamas G, Desaga M, Koenig C, Habedank D, Cobo E, Navarro X, Wiegand U. Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy. Europace. 2014 Jan;16(1):63-70. doi: 10.1093/europace/eut217. Epub 2013 Jul 16.
PMID: 23861381
citation: Brenyo A, Barsheshet A, Rao M, Huang DT, Zareba W, McNitt S, Hall WJ, Peterson DR, Solomon SD, Moss AJ, Goldenberg I. Brain natriuretic peptide and cardiac resynchronization therapy in patients with mildly symptomatic heart failure. Circ Heart Fail. 2013 Sep 1;6(5):998-1004. doi: 10.1161/CIRCHEARTFAILURE.112.000174. Epub 2013 Jun 25.
PMID: 23801020
citation: Shukla A, Curtis AB, Mehra MR, Albert NM, Gheorghiade M, Heywood JT, Liu Y, O'Connor CM, Reynolds D, Walsh MN, Yancy CW, Fonarow GC. Factors associated with improvement in utilization of cardiac resynchronization therapy in eligible heart failure patients: findings from IMPROVE HF. Pacing Clin Electrophysiol. 2013 Apr;36(4):433-43. doi: 10.1111/pace.12090. Epub 2013 Feb 4.
PMID: 23380000
citation: Martin DO, Day JD, Lai PY, Murphy AL, Nayak HM, Villareal RP, Weiner S, Kraus SM, Stolen KQ, Gold MR. Atrial support pacing in heart failure: results from the multicenter PEGASUS CRT trial. J Cardiovasc Electrophysiol. 2012 Dec;23(12):1317-25. doi: 10.1111/j.1540-8167.2012.02402.x. Epub 2012 Jul 25.
PMID: 22830441
responsible party type: Principal Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Dr. Adam Ali Ghotbi
investigator title: MD
mesh term: Heart Failure