<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/NCT04463121</url>
  </required_header>
  <id_info>
    <org_study_id>BBM MOD PV CS-06</org_study_id>
    <nct_id>NCT04463121</nct_id>
  </id_info>
  <brief_title>Preload and Autonomic Responses With Cardiac Neuromodulation Therapy (CNT) (CS-06)</brief_title>
  <acronym>CS-06</acronym>
  <official_title>Pressure-Volume (PV) Measurements for Evaluating the Changes in the Ventricular Preload and Autonomic Nervous System Using BackBeat Medical Cardiac Neuromodulation Therapy (CNT) Signals in an Acute Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BackBeat Medical Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CD Leycom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>BackBeat Medical Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This investigation will evaluate the effect of RV pacing lead position on cardiac function&#xD;
      and the modulation of the autonomic nervous system with Cardiac Neuromodulation Therapy (CNT)&#xD;
      pacing signals. The study will be performed acutely prior to a pacemaker implant.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects indicated for a dual chamber pacemaker implant or replacement who are not 100%&#xD;
      dependent on right ventricular pacing may be eligible to participate in the study.&#xD;
&#xD;
      This investigation will evaluate the effect of RV pacing lead position on cardiac function&#xD;
      and the modulation of the autonomic nervous system using Cardiac Neuromodulation Therapy&#xD;
      (CNT) pacing signals at different positions of the RV pacing lead.&#xD;
&#xD;
      A standard conductance catheter will be introduced through the femoral artery and advanced&#xD;
      into the left ventricle to measure cardiac volumes and pressure.&#xD;
&#xD;
      Arterial blood pressure will be measured from the other femoral artery with an additional&#xD;
      sheath.&#xD;
&#xD;
      The Moderato® IPG will be used to generate Cardiac Neuromodulation Therapy (CNT) signals and&#xD;
      deliver them to the patient through the cable and leads. A range of CNT signal parameters&#xD;
      will be used to assess the effect on sympathetic activity at different positions of the RV&#xD;
      pacing lead. Ventricular pressure and volume readings from the conductance catheter and&#xD;
      arterial pressure readings will be recorded and analyzed to assess the effect of CNT signals&#xD;
      on cardiac function, sympathetic activity and blood pressure.&#xD;
&#xD;
      The effects of CNT signal over a range of parameter settings will be studied for the&#xD;
      different RV lead positions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 7, 2020</start_date>
  <completion_date type="Anticipated">July 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effects of the Moderato CNT pacing signals on cardiac function</measure>
    <time_frame>approximately one hour</time_frame>
    <description>Left ventricular pressure (mmHg) and Volume (ml) will be obtained by a multisensor catheter which provides real-time, beat-to-beat intra-ventricular measurement of cardiac function and performance. Data will be used to generate Pressure-Volume Loops, an aknowledged way to describe hemodynamic changes. CNT signals (alternating short and long atrioventicular sequences 40-150 ms) will be delivered at the same by right ventricular pacemaker leads temporarely connected to the Moderato device.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of CNT pacing signals on blood pressure</measure>
    <time_frame>aproximately onr hour</time_frame>
    <description>Blood pressure (mmHg) will be obtained in parallel with a Millar catheter from the femoral artery througout the study.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Bradycardia</condition>
  <condition>Hypertension, Systolic</condition>
  <arm_group>
    <arm_group_label>Acute CNT pacing signals testing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acute study procedure will be carried out prior to a pacemaker implantation or replacement: pacemaker Right Atrial (RA) and Right Ventricular (RV) leads will be positioned according to standard procedure for pacemaker implant and connected to a Moderato® System IPG, via a single use, sterile Pacing System Analyzer (PSA) cable. The Moderato IPG will deliver CNT signals.&#xD;
Furthermore, a standard conductance catheter in the left ventricle will measure cardiac volumes and pressure. Arterial blood pressure will be obtained as well.&#xD;
A range of CNT signal parameters will be used to assess the effect on sympathetic activity at different positions of the RV pacing lead while ventricular pressure and volume and arteial pressure signals will be assesed for cardiac function, sympathetic activity and blood pressure. The effects of CNT signal over a range of parameter settings will be studied for the different RV lead positions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Moderato IPG's CNT pacing signals</intervention_name>
    <description>Assesment of cardiac function and sympatheric activity will be obtained simultaneously</description>
    <arm_group_label>Acute CNT pacing signals testing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CD Leycom Pressure/Volume Combination Catheters</intervention_name>
    <description>Simultaneous recording of the Pressure, Volume measurements and ECG signals will be done for constant monitoring of intra-ventricular pressure and volume.</description>
    <arm_group_label>Acute CNT pacing signals testing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is ≥ 18 years of age&#xD;
&#xD;
          2. Subject requires implantation or replacement of a dual chamber pacemaker or requires&#xD;
             an upgrade from a single chamber to a dual chamber pacemaker&#xD;
&#xD;
          3. Subject has known Hypertension&#xD;
&#xD;
          4. Subject is willing and able to comply with the study and procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has symptoms of heart failure, NYHA Class II or greater&#xD;
&#xD;
          2. Subject has significant (&gt;2+) mitral regurgitation, aortic regurgitation or aortic&#xD;
             stenosis.&#xD;
&#xD;
          3. Subject has permanent atrial fibrillation&#xD;
&#xD;
          4. Subject has atrial fibrillation on the day of the study.&#xD;
&#xD;
          5. Subject has hypertrophic cardiomyopathy, restrictive cardiomyopathy or&#xD;
             interventricular septal thickness ≥15 mm&#xD;
&#xD;
          6. Subject is on dialysis&#xD;
&#xD;
          7. Subject has a history of prior neurological events (stroke or TIA) within the past&#xD;
             year or a neurological event (stroke or TIA) at any prior time that has resulted in&#xD;
             residual neurologic deficit.&#xD;
&#xD;
          8. Subject has a history of autonomic dysfunction&#xD;
&#xD;
          9. Women who are pregnant or breast-feeding&#xD;
&#xD;
         10. Subject cannot or is unwilling to provide informed consent.&#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>Petr Neuzil, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Na Homolce Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yuval Mika, PhD</last_name>
    <phone>+18569123155</phone>
    <email>ymika@orchestrabiomed.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Norbert Rosenthal</last_name>
    <phone>+491792482543</phone>
    <email>nrosenthal@orchestrabiomed.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Na Homolce Hospital</name>
      <address>
        <city>Praha</city>
        <zip>15030</zip>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Petr Neuzil, MD, PhD</last_name>
      <phone>+420 257272211</phone>
      <email>Peter.Neuzil@homolka.cz</email>
    </contact>
    <contact_backup>
      <last_name>Libor Dujka, MD</last_name>
      <phone>+420731486352</phone>
      <email>libor.dujka@homolka.cz</email>
    </contact_backup>
    <investigator>
      <last_name>Petr Neuzil, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Filip Malek, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jan Petru, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Milan Chovanec, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Libor Dujka, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Czechia</country>
  </location_countries>
  <reference>
    <citation>Yang B, Wang Y, Zhang F, Ju W, Chen H, Mika Y, Aviv R, Evans SJ, Burkhoff D, Wang J, Chen M. Rationale and evidence for the development of a durable device-based cardiac neuromodulation therapy for hypertension. J Am Soc Hypertens. 2018 May;12(5):381-391. doi: 10.1016/j.jash.2018.03.004. Epub 2018 Mar 21.</citation>
    <PMID>29628351</PMID>
  </reference>
  <reference>
    <citation>Neuzil P, Merkely B, Erglis A, Marinskis G, de Groot JR, Schmidinger H, Rodriguez Venegas M, Voskuil M, Sturmberger T, Petru J, Jongejan N, Aichinger J, Kamzola G, Aidietis A, Geller L, Mraz T, Osztheimer I, Mika Y, Evans S, Burkhoff D, Kuck KH; BackBeat Study Investigators. Pacemaker-Mediated Programmable Hypertension Control Therapy. J Am Heart Assoc. 2017 Dec 23;6(12):e006974. doi: 10.1161/JAHA.117.006974.</citation>
    <PMID>29275370</PMID>
  </reference>
  <reference>
    <citation>de Roest GJ, Allaart CP, Kleijn SA, Delnoy PP, Wu L, Hendriks ML, Bronzwaer JG, van Rossum AC, de Cock CC. Prediction of long-term outcome of cardiac resynchronization therapy by acute pressure-volume loop measurements. Eur J Heart Fail. 2013 Mar;15(3):299-307. doi: 10.1093/eurjhf/hfs190. Epub 2012 Nov 25.</citation>
    <PMID>23183349</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>September 15, 2022</last_update_submitted>
  <last_update_submitted_qc>September 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2022</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>Bradycardia</mesh_term>
    <mesh_term>Isolated Systolic 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/NCT04463121
org study id: BBM MOD PV CS-06
nct id: NCT04463121
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This investigation will evaluate the effect of RV pacing lead position on cardiac function
      and the modulation of the autonomic nervous system with Cardiac Neuromodulation Therapy (CNT)
      pacing signals. The study will be performed acutely prior to a pacemaker implant.
Subjects indicated for a dual chamber pacemaker implant or replacement who are not 100%
      dependent on right ventricular pacing may be eligible to participate in the study.

      This investigation will evaluate the effect of RV pacing lead position on cardiac function
      and the modulation of the autonomic nervous system using Cardiac Neuromodulation Therapy
      (CNT) pacing signals at different positions of the RV pacing lead.

      A standard conductance catheter will be introduced through the femoral artery and advanced
      into the left ventricle to measure cardiac volumes and pressure.

      Arterial blood pressure will be measured from the other femoral artery with an additional
      sheath.

      The Moderato® IPG will be used to generate Cardiac Neuromodulation Therapy (CNT) signals and
      deliver them to the patient through the cable and leads. A range of CNT signal parameters
      will be used to assess the effect on sympathetic activity at different positions of the RV
      pacing lead. Ventricular pressure and volume readings from the conductance catheter and
      arterial pressure readings will be recorded and analyzed to assess the effect of CNT signals
      on cardiac function, sympathetic activity and blood pressure.

      The effects of CNT signal over a range of parameter settings will be studied for the
      different RV lead positions.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Effects of the Moderato CNT pacing signals on cardiac function
time frame: approximately one hour
description: Left ventricular pressure (mmHg) and Volume (ml) will be obtained by a multisensor catheter which provides real-time, beat-to-beat intra-ventricular measurement of cardiac function and performance. Data will be used to generate Pressure-Volume Loops, an aknowledged way to describe hemodynamic changes. CNT signals (alternating short and long atrioventicular sequences 40-150 ms) will be delivered at the same by right ventricular pacemaker leads temporarely connected to the Moderato device.
measure: Effects of CNT pacing signals on blood pressure
time frame: aproximately onr hour
description: Blood pressure (mmHg) will be obtained in parallel with a Millar catheter from the femoral artery througout the study.
arm group label: Acute CNT pacing signals testing
arm group type: Experimental
description: Acute study procedure will be carried out prior to a pacemaker implantation or replacement: pacemaker Right Atrial (RA) and Right Ventricular (RV) leads will be positioned according to standard procedure for pacemaker implant and connected to a Moderato® System IPG, via a single use, sterile Pacing System Analyzer (PSA) cable. The Moderato IPG will deliver CNT signals.
Furthermore, a standard conductance catheter in the left ventricle will measure cardiac volumes and pressure. Arterial blood pressure will be obtained as well.
A range of CNT signal parameters will be used to assess the effect on sympathetic activity at different positions of the RV pacing lead while ventricular pressure and volume and arteial pressure signals will be assesed for cardiac function, sympathetic activity and blood pressure. The effects of CNT signal over a range of parameter settings will be studied for the different RV lead positions.
intervention type: Device
intervention name: Moderato IPG's CNT pacing signals
description: Assesment of cardiac function and sympatheric activity will be obtained simultaneously
arm group label: Acute CNT pacing signals testing
intervention type: Device
intervention name: CD Leycom Pressure/Volume Combination Catheters
description: Simultaneous recording of the Pressure, Volume measurements and ECG signals will be done for constant monitoring of intra-ventricular pressure and volume.
arm group label: Acute CNT pacing signals testing
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Petr Neuzil, MD, PhD
role: Principal Investigator
affiliation: Na Homolce Hospital
last name: Yuval Mika, PhD
phone: +18569123155
email: ymika@orchestrabiomed.com
last name: Norbert Rosenthal
phone: +491792482543
email: nrosenthal@orchestrabiomed.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Czechia
citation: Yang B, Wang Y, Zhang F, Ju W, Chen H, Mika Y, Aviv R, Evans SJ, Burkhoff D, Wang J, Chen M. Rationale and evidence for the development of a durable device-based cardiac neuromodulation therapy for hypertension. J Am Soc Hypertens. 2018 May;12(5):381-391. doi: 10.1016/j.jash.2018.03.004. Epub 2018 Mar 21.
PMID: 29628351
citation: Neuzil P, Merkely B, Erglis A, Marinskis G, de Groot JR, Schmidinger H, Rodriguez Venegas M, Voskuil M, Sturmberger T, Petru J, Jongejan N, Aichinger J, Kamzola G, Aidietis A, Geller L, Mraz T, Osztheimer I, Mika Y, Evans S, Burkhoff D, Kuck KH; BackBeat Study Investigators. Pacemaker-Mediated Programmable Hypertension Control Therapy. J Am Heart Assoc. 2017 Dec 23;6(12):e006974. doi: 10.1161/JAHA.117.006974.
PMID: 29275370
citation: de Roest GJ, Allaart CP, Kleijn SA, Delnoy PP, Wu L, Hendriks ML, Bronzwaer JG, van Rossum AC, de Cock CC. Prediction of long-term outcome of cardiac resynchronization therapy by acute pressure-volume loop measurements. Eur J Heart Fail. 2013 Mar;15(3):299-307. doi: 10.1093/eurjhf/hfs190. Epub 2012 Nov 25.
PMID: 23183349
responsible party type: Sponsor
mesh term: Bradycardia
mesh term: Isolated Systolic Hypertension