<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/NCT02203383</url>
  </required_header>
  <id_info>
    <org_study_id>14/LO/0078</org_study_id>
    <nct_id>NCT02203383</nct_id>
  </id_info>
  <brief_title>The Effect of CRT on the Hypercapnic Ventilatory Response</brief_title>
  <official_title>Sleep Disordered Breathing in Patients With Implanted Cardiac Devices: Assessment of the Change in Sensitivity to Carbon Dioxide With Cardiac Resynchronization Therapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Brompton &amp; Harefield NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boston Scientific Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Royal Brompton &amp; Harefield NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Central Sleep Apnoea (CSA) affects up to half of patients with severe heart failure and is&#xD;
      associated with a poor prognosis. CSA is manifest as episodes of deep breathing interspersed&#xD;
      with very shallow or absent breathing and is largely due to an exaggerated response to rising&#xD;
      carbon dioxide in the blood, which normally drives how hard we breathe. Cardiac&#xD;
      Resynchronization therapy (CRT), in which a pacemaker is implanted to improve co-ordinated&#xD;
      contraction of the heart, has been shown to reduce the severity of CSA in some patient&#xD;
      groups. We aim to determine whether this improvement is due to normalization of the body's&#xD;
      response to carbon dioxide in the blood. Our hypothesis is that CRT improves CSA by&#xD;
      normalizing the brain's response to carbon dioxide.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sleep disordered Breathing is common in heart failure, affecting around half of patients.&#xD;
      This may be Obstructive Sleep Apnoea due to loss of pharyngeal muscle tone (OSA, associated&#xD;
      with obesity and snoring and predisposing to hypertension, heart attack and stroke) or&#xD;
      Central Sleep Apnoea (CSA). CSA is particularly prevalent in severe heart failure and&#xD;
      associated with an adverse prognosis. The mechanism involves reflex hyperventilation due to&#xD;
      pulmonary oedema, exaggerated chemosensor response to hypercapnoea associated with increased&#xD;
      sympathetic nervous system activation and a prolonged circulation time.&#xD;
&#xD;
      It is known that CRT improved CSA in 'responders' but the mechanism is unknown. We hypothesis&#xD;
      that CRT normalizes the respiratory response to carbon dioxide (the hypercapnic ventilatory&#xD;
      response - HCVR).&#xD;
&#xD;
      We will screen patients undergoing CRT with an Embletta sleep study to identify a group with&#xD;
      moderate to severe CSA and a group with no sleep apnoea (controls). Patients will undergo&#xD;
      assessment of the hypercapnic ventilatory response with a Read Re-Breathe test prior to&#xD;
      device implantation and 6 weeks and 6 months afterwards. The gradient of minute ventilation&#xD;
      vs PaCO2 will be compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Pending further equipment and staff&#xD;
  </why_stopped>
  <start_date>June 2014</start_date>
  <completion_date type="Anticipated">October 2017</completion_date>
  <primary_completion_date type="Anticipated">October 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The change in gradient of minute ventilation vs end tidal CO2 before and after CRT (the hypercapnic ventilatory response).</measure>
    <time_frame>6 weeks and 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>6 minute walk distance</measure>
    <time_frame>6 weeks and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in resting PaCO2</measure>
    <time_frame>6 weeks and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in left ventricular ejection fraction</measure>
    <time_frame>6 weeks and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasma B-Type Natriuretic Peptide level</measure>
    <time_frame>6 weeks and 6 months</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Sleep Disordered Breathing</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Pts with CSA for CRT implantation</arm_group_label>
    <description>Patients with heart failure (EF&lt;40%) and moderate to severe CSA (&gt;15 events per hour, &gt;50% Central)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Sleep Apnoea for CRT implantation</arm_group_label>
    <description>Heart failure (EF &lt; 40%) but no significant sleep apnoea (&lt;5 events per hour).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CRT Implantation</intervention_name>
    <description>Implantation of a biventricular pacemaker or defibrillator.</description>
    <arm_group_label>No Sleep Apnoea for CRT implantation</arm_group_label>
    <arm_group_label>Pts with CSA for CRT implantation</arm_group_label>
    <other_name>INVIVE</other_name>
    <other_name>INCEPTA</other_name>
    <other_name>AUTOGEN</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with heart failure with reduced ejection fraction (&lt;40% on echocardiography) due&#xD;
        to undergo implantation of a biventricular pacemaker, with either no significant sleep&#xD;
        disordered breathing or moderate to severe CSA.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Heart failure with reduced ejection fraction (&lt;40%)&#xD;
&#xD;
          -  Either no significant sleep disordered breathing or moderate to severe CSA&#xD;
&#xD;
          -  Able to consent to the study&#xD;
&#xD;
          -  Ambulatory&#xD;
&#xD;
          -  Aged 18-100 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients on Non-Invasive Ventilation&#xD;
&#xD;
          -  Predominant OSA&#xD;
&#xD;
          -  Unable to consent or attend for the study&#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>Ali Vazir, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College. Royal Brompton Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Martin Cowie, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Brompton and Harefield NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SW6 6NP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>November 8, 2016</last_update_submitted>
  <last_update_submitted_qc>November 8, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 9, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cardiac Resynchronization Therapy</keyword>
  <keyword>Central Sleep Apnoea</keyword>
  <keyword>Sleep Disordered Breathing</keyword>
  <keyword>Heart Failure</keyword>
  <keyword>Hypercapnic Ventilatory Response</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Aspiration</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <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/NCT02203383
org study id: 14/LO/0078
nct id: NCT02203383
lead sponsor: 
collaborator: 
has dmc: Yes
Central Sleep Apnoea (CSA) affects up to half of patients with severe heart failure and is
      associated with a poor prognosis. CSA is manifest as episodes of deep breathing interspersed
      with very shallow or absent breathing and is largely due to an exaggerated response to rising
      carbon dioxide in the blood, which normally drives how hard we breathe. Cardiac
      Resynchronization therapy (CRT), in which a pacemaker is implanted to improve co-ordinated
      contraction of the heart, has been shown to reduce the severity of CSA in some patient
      groups. We aim to determine whether this improvement is due to normalization of the body's
      response to carbon dioxide in the blood. Our hypothesis is that CRT improves CSA by
      normalizing the brain's response to carbon dioxide.
Sleep disordered Breathing is common in heart failure, affecting around half of patients.
      This may be Obstructive Sleep Apnoea due to loss of pharyngeal muscle tone (OSA, associated
      with obesity and snoring and predisposing to hypertension, heart attack and stroke) or
      Central Sleep Apnoea (CSA). CSA is particularly prevalent in severe heart failure and
      associated with an adverse prognosis. The mechanism involves reflex hyperventilation due to
      pulmonary oedema, exaggerated chemosensor response to hypercapnoea associated with increased
      sympathetic nervous system activation and a prolonged circulation time.

      It is known that CRT improved CSA in 'responders' but the mechanism is unknown. We hypothesis
      that CRT normalizes the respiratory response to carbon dioxide (the hypercapnic ventilatory
      response - HCVR).

      We will screen patients undergoing CRT with an Embletta sleep study to identify a group with
      moderate to severe CSA and a group with no sleep apnoea (controls). Patients will undergo
      assessment of the hypercapnic ventilatory response with a Read Re-Breathe test prior to
      device implantation and 6 weeks and 6 months afterwards. The gradient of minute ventilation
      vs PaCO2 will be compared.
observational model: Case-Control
time perspective: Prospective
measure: The change in gradient of minute ventilation vs end tidal CO2 before and after CRT (the hypercapnic ventilatory response).
time frame: 6 weeks and 6 months
measure: 6 minute walk distance
time frame: 6 weeks and 6 months
measure: Change in resting PaCO2
time frame: 6 weeks and 6 months
measure: Change in left ventricular ejection fraction
time frame: 6 weeks and 6 months
measure: Change in plasma B-Type Natriuretic Peptide level
time frame: 6 weeks and 6 months
arm group label: Pts with CSA for CRT implantation
description: Patients with heart failure (EF<40%) and moderate to severe CSA (>15 events per hour, >50% Central)
arm group label: No Sleep Apnoea for CRT implantation
description: Heart failure (EF < 40%) but no significant sleep apnoea (<5 events per hour).
intervention type: Device
intervention name: CRT Implantation
description: Implantation of a biventricular pacemaker or defibrillator.
arm group label: No Sleep Apnoea for CRT implantation
arm group label: Pts with CSA for CRT implantation
other name: INVIVE
other name: INCEPTA
other name: AUTOGEN
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ali Vazir, PhD
role: Principal Investigator
affiliation: Imperial College. Royal Brompton Hospital
last name: Martin Cowie, MD
role: Study Chair
affiliation: Imperial College London
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Respiratory Aspiration
mesh term: Sleep Apnea Syndromes
mesh term: Heart Failure