<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/NCT03255408</url>
  </required_header>
  <id_info>
    <org_study_id>REB13-0880</org_study_id>
    <nct_id>NCT03255408</nct_id>
  </id_info>
  <brief_title>Cerebral Blood Flow and Ventilatory Responses During Sleep in Normoxia and Intermittent Hypoxia</brief_title>
  <official_title>Role of Cerebral Blood Flow on Ventilatory Stability During Sleep in Normoxia and Intermittent Hypoxia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Calgary</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective double blind, placebo-controlled, randomized cross-over trial to evaluate the&#xD;
      effect of lowering cerebral blood flow on the ventilatory chemoreflexes (acute hypoxic and&#xD;
      hypercapnic ventilatory responses).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will explore the relationship between changes in Cerebral Blood Flow (CBF)&#xD;
      and ventilatory chemoreflexes i.e. Acute Ventilatory Response to Hypoxia (AHVR) and Acute&#xD;
      Hypercapnic Ventilatory Response (HCVR) before, during and after sleep under normoxic&#xD;
      conditions and sleep accompanied by isocapnic Intermittent Hypoxia (IH) among healthy human&#xD;
      study participants.&#xD;
&#xD;
      A pharmacological intervention will be utilized to manipulate the CBF in a randomized order.&#xD;
      The study participants will also be randomly assigned the order to sleep either under&#xD;
      normoxia or IH exposure. The experiments will be separated from one another with an interval&#xD;
      of sufficient drug and IH exposure washout period. The venous blood samples and urinary&#xD;
      samples will be collected for the vascular biomarkers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">January 1, 2023</start_date>
  <completion_date type="Anticipated">December 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in cerebral blood flow and ventilatory chemoreflexes</measure>
    <time_frame>~18 months (from the starting time of recruiting study participants)</time_frame>
    <description>The relationship between changes in cerebral blood flow (CBF) and ventilatory chemoreflexes (acute hypoxic and hypercapnic ventilatory responses) before and after sleeping under normoxia and intermittent hypoxia exposure among healthy human study participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cerebral blood flow responses and ventilatory chemoreflexes during sleep</measure>
    <time_frame>~18 months (from the starting time of recruiting study participants)</time_frame>
    <description>The relationship between cerebral blood flow (CBF) changes and ventilatory chemoreflexes (acute hypoxic and hypercapnic ventilatory responses) during sleep under normoxia and intermittent hypoxia exposure among healthy human study participants.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in reactive oxygen species and vascular biomarkers</measure>
    <time_frame>~24 months (from the starting time of recruiting study participants)</time_frame>
    <description>The changes in vascular biomarkers such as nitric oxide, reactive oxygen species and exosome analysis or urinary prostaglandins before and after sleep under normoxia and intermittent hypoxia exposure with cerebral blood flow changes.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Obstructive Sleep Apnea of Adult</condition>
  <condition>Hypoxia, Brain</condition>
  <condition>Sleep Apnea</condition>
  <condition>Sleep Disorder</condition>
  <condition>Stroke</condition>
  <condition>Blood Pressure</condition>
  <condition>Endothelial Dysfunction</condition>
  <condition>Oxidative Stress</condition>
  <arm_group>
    <arm_group_label>CBF Lowering and Normoxia Sleep</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Study participants will take drug lowering Cerebral Blood Flow (CBF) and sleep under room air i.e. normoxia exposure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CBF Lowering and IH Sleep</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study participants will take drug lowering Cerebral Blood Flow (CBF) and sleep under Intermittent Hypoxia (IH) exposure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and Normoxia Sleep</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Study participants will take Placebo that has no effect on Cerebral Blood Flow (CBF) and sleep under room air i.e. normoxia exposure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and IH Sleep</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Study participants will take Placebo that has no effect on Cerebral Blood Flow (CBF) and sleep under Intermittent Hypoxia (IH) exposure.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Drug Lowering Cerebral Blood Flow (CBF) and Normoxia Sleep</intervention_name>
    <description>The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Normoxia Exposure</description>
    <arm_group_label>CBF Lowering and Normoxia Sleep</arm_group_label>
    <other_name>Cerebral Blood Flow changes and Normoxia Sleep</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Drug Lowering CBF and Intermittent Hypoxia Sleep</intervention_name>
    <description>The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Intermittent Hypoxia (IH) Exposure</description>
    <arm_group_label>CBF Lowering and IH Sleep</arm_group_label>
    <other_name>CBF changes and Intermittent Hypoxia Sleep</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo and Normoxia Sleep</intervention_name>
    <description>The study participants will take Placebo and sleep under Normoxia Exposure</description>
    <arm_group_label>Placebo and Normoxia Sleep</arm_group_label>
    <other_name>Cerebral Blood Flow (CBF) with Placebo in Normoxia Sleep</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo and Intermittent Hypoxia Sleep</intervention_name>
    <description>The study participants will take Placebo and sleep under Intermittent Hypoxia (IH) Exposure</description>
    <arm_group_label>Placebo and IH Sleep</arm_group_label>
    <other_name>CBF with Placebo in Intermittent Hypoxia Sleep</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adults&#xD;
&#xD;
          -  18 - 45 years of age&#xD;
&#xD;
          -  Living in Calgary for the past one year&#xD;
&#xD;
          -  Have no medical condition or should not be taking any blood pressure medications.&#xD;
&#xD;
          -  The participant should not be lactose intolerant&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cerebrovascular, cardio-respiratory, renal and metabolic diseases&#xD;
&#xD;
          -  Bleeding disorders and upper gastrointestinal diseases e.g. peptic ulcer disease&#xD;
&#xD;
          -  Pregnancy, obese and sleep-disordered breathing&#xD;
&#xD;
          -  Drug allergies to non-steroidal anti-inflammatories&#xD;
&#xD;
          -  Currently smoking&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 6, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>November 2, 2022</last_update_submitted>
  <last_update_submitted_qc>November 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Calgary</investigator_affiliation>
    <investigator_full_name>Marc Poulin</investigator_full_name>
    <investigator_title>PhD, DPhil, Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
    <mesh_term>Sleep Wake Disorders</mesh_term>
    <mesh_term>Hypoxia, Brain</mesh_term>
    <mesh_term>Hypoxia</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/NCT03255408
org study id: REB13-0880
nct id: NCT03255408
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
A prospective double blind, placebo-controlled, randomized cross-over trial to evaluate the
      effect of lowering cerebral blood flow on the ventilatory chemoreflexes (acute hypoxic and
      hypercapnic ventilatory responses).
The investigators will explore the relationship between changes in Cerebral Blood Flow (CBF)
      and ventilatory chemoreflexes i.e. Acute Ventilatory Response to Hypoxia (AHVR) and Acute
      Hypercapnic Ventilatory Response (HCVR) before, during and after sleep under normoxic
      conditions and sleep accompanied by isocapnic Intermittent Hypoxia (IH) among healthy human
      study participants.

      A pharmacological intervention will be utilized to manipulate the CBF in a randomized order.
      The study participants will also be randomly assigned the order to sleep either under
      normoxia or IH exposure. The experiments will be separated from one another with an interval
      of sufficient drug and IH exposure washout period. The venous blood samples and urinary
      samples will be collected for the vascular biomarkers.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Changes in cerebral blood flow and ventilatory chemoreflexes
time frame: ~18 months (from the starting time of recruiting study participants)
description: The relationship between changes in cerebral blood flow (CBF) and ventilatory chemoreflexes (acute hypoxic and hypercapnic ventilatory responses) before and after sleeping under normoxia and intermittent hypoxia exposure among healthy human study participants.
measure: Cerebral blood flow responses and ventilatory chemoreflexes during sleep
time frame: ~18 months (from the starting time of recruiting study participants)
description: The relationship between cerebral blood flow (CBF) changes and ventilatory chemoreflexes (acute hypoxic and hypercapnic ventilatory responses) during sleep under normoxia and intermittent hypoxia exposure among healthy human study participants.
measure: Changes in reactive oxygen species and vascular biomarkers
time frame: ~24 months (from the starting time of recruiting study participants)
description: The changes in vascular biomarkers such as nitric oxide, reactive oxygen species and exosome analysis or urinary prostaglandins before and after sleep under normoxia and intermittent hypoxia exposure with cerebral blood flow changes.
arm group label: CBF Lowering and Normoxia Sleep
arm group type: Active Comparator
description: Study participants will take drug lowering Cerebral Blood Flow (CBF) and sleep under room air i.e. normoxia exposure.
arm group label: CBF Lowering and IH Sleep
arm group type: Experimental
description: Study participants will take drug lowering Cerebral Blood Flow (CBF) and sleep under Intermittent Hypoxia (IH) exposure.
arm group label: Placebo and Normoxia Sleep
arm group type: Sham Comparator
description: Study participants will take Placebo that has no effect on Cerebral Blood Flow (CBF) and sleep under room air i.e. normoxia exposure.
arm group label: Placebo and IH Sleep
arm group type: Placebo Comparator
description: Study participants will take Placebo that has no effect on Cerebral Blood Flow (CBF) and sleep under Intermittent Hypoxia (IH) exposure.
intervention type: Drug
intervention name: Drug Lowering Cerebral Blood Flow (CBF) and Normoxia Sleep
description: The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Normoxia Exposure
arm group label: CBF Lowering and Normoxia Sleep
other name: Cerebral Blood Flow changes and Normoxia Sleep
intervention type: Drug
intervention name: Drug Lowering CBF and Intermittent Hypoxia Sleep
description: The study participants will take Cerebral Blood Flow (CBF) lowering drug and sleep under Intermittent Hypoxia (IH) Exposure
arm group label: CBF Lowering and IH Sleep
other name: CBF changes and Intermittent Hypoxia Sleep
intervention type: Drug
intervention name: Placebo and Normoxia Sleep
description: The study participants will take Placebo and sleep under Normoxia Exposure
arm group label: Placebo and Normoxia Sleep
other name: Cerebral Blood Flow (CBF) with Placebo in Normoxia Sleep
intervention type: Drug
intervention name: Placebo and Intermittent Hypoxia Sleep
description: The study participants will take Placebo and sleep under Intermittent Hypoxia (IH) Exposure
arm group label: Placebo and IH Sleep
other name: CBF with Placebo in Intermittent Hypoxia Sleep
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Principal Investigator
investigator affiliation: University of Calgary
investigator full name: Marc Poulin
investigator title: PhD, DPhil, Professor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Sleep Wake Disorders
mesh term: Hypoxia, Brain
mesh term: Hypoxia