<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/NCT01723189</url>
  </required_header>
  <id_info>
    <org_study_id>EOC.NSI.12.04</org_study_id>
    <nct_id>NCT01723189</nct_id>
  </id_info>
  <brief_title>Pathophysiology of Central Apnoeas in Stroke Patients</brief_title>
  <official_title>Central Apnoeas in the Course of Transient Ischemic Attack/Ischemic Stroke: Clinical, Prognostic, Pathophysiological Elements.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MPons</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Advisory Board of scientific Reserch Ente Ospedaliero Cantonale, ABREOC</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Geneva, Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Milan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ospedale Civico, Lugano</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      40% of patients with Sleep Disorder Breathing (SDB) appearing during the acute phase of&#xD;
      stroke show a respiratory pattern characterized by central apnoeas and/or periodic breathing.&#xD;
&#xD;
      Clinical studies conducted in patients with hearth failure and central apnoeas have&#xD;
      demonstrated the pathogenetic central role of hypersensitivity of central and peripheral&#xD;
      chemoreceptors in association with baroreflex hypersensitivity, expression of hyperactivity&#xD;
      of sympathetic nervous system.&#xD;
&#xD;
      The joint study of chemoreflexes and baroreflexes in patients with central apneas during the&#xD;
      acute and subacute phase of ischemic stroke represents, to our knowledge, a novelty in&#xD;
      literature, that should supply useful elements to clarify the pathogenesis and the clinical&#xD;
      and prognostic significance of these disorders.&#xD;
&#xD;
      Investigators expect a difference in the analysis of the baroreflexes and chemoreflexes in&#xD;
      patients with ischemic stroke/transient ischemic attack (TIA) and central apnoeas than&#xD;
      patients with ischemic stroke not accompanied by respiratory problems and compared with&#xD;
      healthy controls.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Investigators expected to include in the study of 120 patients, aged between 35 and 75 years,&#xD;
      belonging to the following diagnostic categories:&#xD;
&#xD;
        -  30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence&#xD;
           at polysomnography of central apnoea (central apnoea index&gt; 10 / h, or Cheyne-Stokes&#xD;
           breathing for more than 30% of total sleep time or mixed apneas with central apnoeas&gt;&#xD;
           50% of total apneas)&#xD;
&#xD;
        -  30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence&#xD;
           at polysomnography of obstructive sleep apnea (apnea-hypopnea index&gt; 20 / h)&#xD;
&#xD;
        -  30 patients diagnosed with TIA / stroke within 7 days of admission and no evidence of&#xD;
           sleep respiratory disorders at polysomnography&#xD;
&#xD;
        -  30 healthy controls matched for age, sex, race and BMI.&#xD;
&#xD;
      For the study of the baroreflexes, patients will be subjected to continuous monitoring of&#xD;
      ECG, beat-to-beat blood pressure measured at the finger by Portapress system, respiratory&#xD;
      rate and ventilation by pneumotachograph. The tests will be performed in the supine position&#xD;
      and then repeated in a sitting position. Data from such monitoring will be used for analysis&#xD;
      of the harmonic components of the cardiac rate (RR interval) and the variability of blood&#xD;
      pressure and respiratory rate, through the method of auto regressive analysis.&#xD;
&#xD;
      For the study of central chemoreceptors, investigator will use the steady-state hypercapnic&#xD;
      test, which measures the ventilatory response to hypercapnia at a constant level of Oxygen&#xD;
      partial pressure (PaO2). The ventilatory response to hypercapnia is calculated by the method&#xD;
      of linear regression and is represented by the angular coefficient of the straight line that&#xD;
      describes the variation of ventilation for each variation of alveolar carbon dioxide partial&#xD;
      pressure (PCO2).&#xD;
&#xD;
      For the study of peripheral chemoreceptors will be used the single-breath or transient&#xD;
      hypercapnia test. The patient makes a single deep breath of a gas mixture containing 85% O2&#xD;
      and 15% CO2 and then resume normal breathing. It is expected, therefore, a period of 3&#xD;
      seconds, required because the gases contained in the mixture may come from the pulmonary&#xD;
      circulation to the peripheral circulation, at the level of peripheral chemoreceptors. The&#xD;
      ventilation is recorded within the next 20-30 seconds, because in this time interval is&#xD;
      evaluated only the sensitivity of the peripheral chemoreceptors, being the latency of&#xD;
      response of the central chemoreceptors greater than 1 minute.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">August 2014</completion_date>
  <primary_completion_date type="Anticipated">August 2014</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>Baroreflexes</measure>
    <time_frame>3 months</time_frame>
    <description>For the study of the baroreflexes, patients will be subjected to continuous monitoring of ECG, beat-to-beat blood pressure measured at the finger by Portapress system, respiratory rate and ventilation by pneumotachograph. The tests will be performed in the supine position and then repeated in a sitting position. Data from such monitoring will be used for analysis of the harmonic components of the RR interval and the variability of blood pressure and respiratory rate, through the method of auto regressive analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chemoreflexes</measure>
    <time_frame>3 months</time_frame>
    <description>For the study of central and peripheral chemoreceptors, investigator will use the steady-state hypercapnic test, which measures the ventilatory response to hypercapnia at a constant level of PaO2, and the single-breath test in wich the subject makes a single deep breath of a gas mixture containing 85% O2 and 15% CO2 and then resume normal breathing. The ventilation is recorded within the next 20-30 seconds, because in this time interval is evaluated only the sensitivity of the peripheral chemoreceptors, being the latency of response of the central chemoreceptors greater than 1 minute.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Apnoea-hypopnoea index (AHI)</measure>
    <time_frame>3 months</time_frame>
    <description>Assessing prognosis and spontaneous temporal evolution of central apnoeas in patients with cerebral ischemic events.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Central Apnoeas</condition>
  <condition>Stroke Patients</condition>
  <arm_group>
    <arm_group_label>Central Apnoeas Patients</arm_group_label>
    <description>• 30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence at polysomnography of central apnoea (central apnoea index&gt; 10 / h, or Cheyne-Stokes breathing for more than 30% of total sleep time or mixed apneas with central apnoeas&gt; 50% of total apneas)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Obstructive apnoea patients</arm_group_label>
    <description>• 30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence at polysomnography of obstructive sleep apnea (apnea-hypopnea index&gt; 20 / h)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No SDB patients</arm_group_label>
    <description>• 30 patients diagnosed with TIA / stroke within 7 days of admission and no evidence of sleep respiratory disorders at polysomnography</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy controls</arm_group_label>
    <description>• 30 healthy controls matched for age, sex, race and BMI.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Primary care clinic&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients&#xD;
&#xD;
               -  ≥35 years old and &lt; 75 years old&#xD;
&#xD;
               -  with clinical diagnosis of TIA or ischemic stroke&#xD;
&#xD;
               -  admitted in a Stroke Unit within 2 days from onset of symptoms&#xD;
&#xD;
               -  signed Informed Consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients&#xD;
&#xD;
               -  with unstable clinical situation (cardio-respiratory or life-threatening medical&#xD;
                  conditions)&#xD;
&#xD;
               -  currently on continuous positive airway pressure (CPAP) or on CPAP during the&#xD;
                  last 3 months before stroke&#xD;
&#xD;
               -  with non-ischemic events (intracerebral/subarachnoid haemorrhage)&#xD;
&#xD;
               -  Patients with coma/stupor&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marco Pons, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ospedale Regionale di Lugano - Civico</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marco Pons, Professor</last_name>
    <phone>0041-91-8116449</phone>
    <email>marco.pons@eoc.ch</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Alessia Riglietti, MD</last_name>
    <phone>0041-91-8116317</phone>
    <email>alessia.riglietti@eoc.ch</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ospedale Civico</name>
      <address>
        <city>Lugano</city>
        <state>Ticino</state>
        <zip>6903</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marco Pons, MD</last_name>
      <phone>+41 91 811 6449</phone>
      <email>marco.pons@eoc.ch</email>
    </contact>
    <contact_backup>
      <last_name>Alessia Riglietti, MD</last_name>
      <phone>+41 91 811 6317</phone>
      <email>alessia.riglietti@eoc.ch</email>
    </contact_backup>
    <investigator>
      <last_name>Marco Pons, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alessia Riglietti, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <link>
    <url>http://www.eoc.ch</url>
    <description>Homepage of study center</description>
  </link>
  <reference>
    <citation>Bassetti CL. Sleep and stroke. Semin Neurol. 2005 Mar;25(1):19-32. doi: 10.1055/s-2005-867073.</citation>
    <PMID>15798934</PMID>
  </reference>
  <reference>
    <citation>Giannoni A, Emdin M, Poletti R, Bramanti F, Prontera C, Piepoli M, Passino C. Clinical significance of chemosensitivity in chronic heart failure: influence on neurohormonal derangement, Cheyne-Stokes respiration and arrhythmias. Clin Sci (Lond). 2008 Apr;114(7):489-97. doi: 10.1042/CS20070292.</citation>
    <PMID>17961123</PMID>
  </reference>
  <reference>
    <citation>Nopmaneejumruslers C, Kaneko Y, Hajek V, Zivanovic V, Bradley TD. Cheyne-Stokes respiration in stroke: relationship to hypocapnia and occult cardiac dysfunction. Am J Respir Crit Care Med. 2005 May 1;171(9):1048-52. doi: 10.1164/rccm.200411-1591OC. Epub 2005 Jan 21.</citation>
    <PMID>15665317</PMID>
  </reference>
  <reference>
    <citation>Siccoli MM, Valko PO, Hermann DM, Bassetti CL. Central periodic breathing during sleep in 74 patients with acute ischemic stroke - neurogenic and cardiogenic factors. J Neurol. 2008 Nov;255(11):1687-92. doi: 10.1007/s00415-008-0981-9. Epub 2008 Nov 13.</citation>
    <PMID>19009334</PMID>
  </reference>
  <reference>
    <citation>Robinson TG, James M, Youde J, Panerai R, Potter J. Cardiac baroreceptor sensitivity is impaired after acute stroke. Stroke. 1997 Sep;28(9):1671-6. doi: 10.1161/01.str.28.9.1671.</citation>
    <PMID>9303008</PMID>
  </reference>
  <reference>
    <citation>Eames PJ, Blake MJ, Dawson SL, Panerai RB, Potter JF. Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke. J Neurol Neurosurg Psychiatry. 2002 Apr;72(4):467-72. doi: 10.1136/jnnp.72.4.467.</citation>
    <PMID>11909905</PMID>
  </reference>
  <reference>
    <citation>Sykora M, Diedler J, Turcani P, Hacke W, Steiner T. Baroreflex: a new therapeutic target in human stroke? Stroke. 2009 Dec;40(12):e678-82. doi: 10.1161/STROKEAHA.109.565838. Epub 2009 Oct 15.</citation>
    <PMID>19834010</PMID>
  </reference>
  <reference>
    <citation>Yumino D, Bradley TD. Central sleep apnea and Cheyne-Stokes respiration. Proc Am Thorac Soc. 2008 Feb 15;5(2):226-36. doi: 10.1513/pats.200708-129MG.</citation>
    <PMID>18250216</PMID>
  </reference>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>October 19, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 7, 2012</study_first_posted>
  <last_update_submitted>November 5, 2012</last_update_submitted>
  <last_update_submitted_qc>November 5, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 7, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ospedale Civico, Lugano</investigator_affiliation>
    <investigator_full_name>MPons</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>central apnoeas</keyword>
  <keyword>stroke</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea, Central</mesh_term>
    <mesh_term>Stroke</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/NCT01723189
org study id: EOC.NSI.12.04
nct id: NCT01723189
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
40% of patients with Sleep Disorder Breathing (SDB) appearing during the acute phase of
      stroke show a respiratory pattern characterized by central apnoeas and/or periodic breathing.

      Clinical studies conducted in patients with hearth failure and central apnoeas have
      demonstrated the pathogenetic central role of hypersensitivity of central and peripheral
      chemoreceptors in association with baroreflex hypersensitivity, expression of hyperactivity
      of sympathetic nervous system.

      The joint study of chemoreflexes and baroreflexes in patients with central apneas during the
      acute and subacute phase of ischemic stroke represents, to our knowledge, a novelty in
      literature, that should supply useful elements to clarify the pathogenesis and the clinical
      and prognostic significance of these disorders.

      Investigators expect a difference in the analysis of the baroreflexes and chemoreflexes in
      patients with ischemic stroke/transient ischemic attack (TIA) and central apnoeas than
      patients with ischemic stroke not accompanied by respiratory problems and compared with
      healthy controls.
Investigators expected to include in the study of 120 patients, aged between 35 and 75 years,
      belonging to the following diagnostic categories:

        -  30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence
           at polysomnography of central apnoea (central apnoea index> 10 / h, or Cheyne-Stokes
           breathing for more than 30% of total sleep time or mixed apneas with central apnoeas>
           50% of total apneas)

        -  30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence
           at polysomnography of obstructive sleep apnea (apnea-hypopnea index> 20 / h)

        -  30 patients diagnosed with TIA / stroke within 7 days of admission and no evidence of
           sleep respiratory disorders at polysomnography

        -  30 healthy controls matched for age, sex, race and BMI.

      For the study of the baroreflexes, patients will be subjected to continuous monitoring of
      ECG, beat-to-beat blood pressure measured at the finger by Portapress system, respiratory
      rate and ventilation by pneumotachograph. The tests will be performed in the supine position
      and then repeated in a sitting position. Data from such monitoring will be used for analysis
      of the harmonic components of the cardiac rate (RR interval) and the variability of blood
      pressure and respiratory rate, through the method of auto regressive analysis.

      For the study of central chemoreceptors, investigator will use the steady-state hypercapnic
      test, which measures the ventilatory response to hypercapnia at a constant level of Oxygen
      partial pressure (PaO2). The ventilatory response to hypercapnia is calculated by the method
      of linear regression and is represented by the angular coefficient of the straight line that
      describes the variation of ventilation for each variation of alveolar carbon dioxide partial
      pressure (PCO2).

      For the study of peripheral chemoreceptors will be used the single-breath or transient
      hypercapnia test. The patient makes a single deep breath of a gas mixture containing 85% O2
      and 15% CO2 and then resume normal breathing. It is expected, therefore, a period of 3
      seconds, required because the gases contained in the mixture may come from the pulmonary
      circulation to the peripheral circulation, at the level of peripheral chemoreceptors. The
      ventilation is recorded within the next 20-30 seconds, because in this time interval is
      evaluated only the sensitivity of the peripheral chemoreceptors, being the latency of
      response of the central chemoreceptors greater than 1 minute.
observational model: Case-Control
time perspective: Prospective
measure: Baroreflexes
time frame: 3 months
description: For the study of the baroreflexes, patients will be subjected to continuous monitoring of ECG, beat-to-beat blood pressure measured at the finger by Portapress system, respiratory rate and ventilation by pneumotachograph. The tests will be performed in the supine position and then repeated in a sitting position. Data from such monitoring will be used for analysis of the harmonic components of the RR interval and the variability of blood pressure and respiratory rate, through the method of auto regressive analysis.
measure: Chemoreflexes
time frame: 3 months
description: For the study of central and peripheral chemoreceptors, investigator will use the steady-state hypercapnic test, which measures the ventilatory response to hypercapnia at a constant level of PaO2, and the single-breath test in wich the subject makes a single deep breath of a gas mixture containing 85% O2 and 15% CO2 and then resume normal breathing. The ventilation is recorded within the next 20-30 seconds, because in this time interval is evaluated only the sensitivity of the peripheral chemoreceptors, being the latency of response of the central chemoreceptors greater than 1 minute.
measure: Apnoea-hypopnoea index (AHI)
time frame: 3 months
description: Assessing prognosis and spontaneous temporal evolution of central apnoeas in patients with cerebral ischemic events.
arm group label: Central Apnoeas Patients
description: • 30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence at polysomnography of central apnoea (central apnoea index> 10 / h, or Cheyne-Stokes breathing for more than 30% of total sleep time or mixed apneas with central apnoeas> 50% of total apneas)
arm group label: Obstructive apnoea patients
description: • 30 patients diagnosed with TIA / ischemic stroke within 7 days of admission and evidence at polysomnography of obstructive sleep apnea (apnea-hypopnea index> 20 / h)
arm group label: No SDB patients
description: • 30 patients diagnosed with TIA / stroke within 7 days of admission and no evidence of sleep respiratory disorders at polysomnography
arm group label: Healthy controls
description: • 30 healthy controls matched for age, sex, race and BMI.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 35 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marco Pons, MD
role: Principal Investigator
affiliation: Ospedale Regionale di Lugano - Civico
last name: Marco Pons, Professor
phone: 0041-91-8116449
email: marco.pons@eoc.ch
last name: Alessia Riglietti, MD
phone: 0041-91-8116317
email: alessia.riglietti@eoc.ch
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Switzerland
url: http://www.eoc.ch
description: Homepage of study center
citation: Bassetti CL. Sleep and stroke. Semin Neurol. 2005 Mar;25(1):19-32. doi: 10.1055/s-2005-867073.
PMID: 15798934
citation: Giannoni A, Emdin M, Poletti R, Bramanti F, Prontera C, Piepoli M, Passino C. Clinical significance of chemosensitivity in chronic heart failure: influence on neurohormonal derangement, Cheyne-Stokes respiration and arrhythmias. Clin Sci (Lond). 2008 Apr;114(7):489-97. doi: 10.1042/CS20070292.
PMID: 17961123
citation: Nopmaneejumruslers C, Kaneko Y, Hajek V, Zivanovic V, Bradley TD. Cheyne-Stokes respiration in stroke: relationship to hypocapnia and occult cardiac dysfunction. Am J Respir Crit Care Med. 2005 May 1;171(9):1048-52. doi: 10.1164/rccm.200411-1591OC. Epub 2005 Jan 21.
PMID: 15665317
citation: Siccoli MM, Valko PO, Hermann DM, Bassetti CL. Central periodic breathing during sleep in 74 patients with acute ischemic stroke - neurogenic and cardiogenic factors. J Neurol. 2008 Nov;255(11):1687-92. doi: 10.1007/s00415-008-0981-9. Epub 2008 Nov 13.
PMID: 19009334
citation: Robinson TG, James M, Youde J, Panerai R, Potter J. Cardiac baroreceptor sensitivity is impaired after acute stroke. Stroke. 1997 Sep;28(9):1671-6. doi: 10.1161/01.str.28.9.1671.
PMID: 9303008
citation: Eames PJ, Blake MJ, Dawson SL, Panerai RB, Potter JF. Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke. J Neurol Neurosurg Psychiatry. 2002 Apr;72(4):467-72. doi: 10.1136/jnnp.72.4.467.
PMID: 11909905
citation: Sykora M, Diedler J, Turcani P, Hacke W, Steiner T. Baroreflex: a new therapeutic target in human stroke? Stroke. 2009 Dec;40(12):e678-82. doi: 10.1161/STROKEAHA.109.565838. Epub 2009 Oct 15.
PMID: 19834010
citation: Yumino D, Bradley TD. Central sleep apnea and Cheyne-Stokes respiration. Proc Am Thorac Soc. 2008 Feb 15;5(2):226-36. doi: 10.1513/pats.200708-129MG.
PMID: 18250216
responsible party type: Sponsor-Investigator
investigator affiliation: Ospedale Civico, Lugano
investigator full name: MPons
investigator title: Professor
mesh term: Apnea
mesh term: Sleep Apnea, Central
mesh term: Stroke