<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/NCT03031626</url>
  </required_header>
  <id_info>
    <org_study_id>1000053577</org_study_id>
    <nct_id>NCT03031626</nct_id>
  </id_info>
  <brief_title>Oxygen Versus Medical Air for Treatment of CSA in Prader Will Syndrome</brief_title>
  <official_title>Comparison of Therapeutic Oxygen Versus Medical Air for the Treatment of Central Sleep Apnea in Infants and Children With Prader Willi Syndrome: A Proof of Concept Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Hospital for Sick Children</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The aim of this study is to determine if treatment with Medical Air (21% oxygen in room air)&#xD;
      compared to supplemental oxygen (100% oxygen) will lead to similar improvements in the&#xD;
      central apnea-hypopnea index (CAHI) for infants with Prader-Willi Syndrome.&#xD;
&#xD;
      Despite the vast amount of research investigating the cause of central sleep apnea, there&#xD;
      remain gaps in knowledge, lending to further research efforts. The decision to compare oxygen&#xD;
      to medical air is based on several theorized mechanisms. The first of which is the&#xD;
      supposition that provision of medical air may act as an arousal stimulus for the&#xD;
      hypothalamus, thereby preventing sleep disordered breathing. Secondly, the hypercapnic&#xD;
      challenge performed by Livingston et al demonstrated a delayed hypercapneic arousal response&#xD;
      in PWS subjects despite simultaneous hyperoxia, leading us to question if therapeutic oxygen&#xD;
      really plays a significant role in treating CSA. Lastly, the delivery of medical air via&#xD;
      nasal prongs may provide sufficient arousal to terminate the cycle of events leading to&#xD;
      central apnea, as described by Urquhart et al.&#xD;
&#xD;
      A deeper understanding of central sleep apnea is essential to ameliorating its adverse&#xD;
      sequelae, which include symptoms of ADHD, impaired attention, behavioral problems, and&#xD;
      academic difficulties.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2016</start_date>
  <completion_date type="Anticipated">December 15, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 15, 2023</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>The screening visit will occur during a regularly scheduled clinic visit. The patients that have consented for the study will all undergo the baseline PSG. Only patients with clinically significant CSA after Visit 1 will undergo randomization and complete Visit 2.&#xD;
Those who have a CAHI greater or equal to 5 will be randomly assigned to Arm A or Arm B. Randomization will be performed using a computer with random numbers drawn. Arm A will receive Medical Air followed by Oxygen and Arm B will receive Oxygen followed by Medical Air.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The split-night polysomnograms (Arm A, Arm B) will be scored by a blinded independent sleep technologist. A Sleep Physician will report the sleep study and be blinded as to the gas assignment (ie Arm A or Arm B).</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Delta CAHI1</measure>
    <time_frame>2 years</time_frame>
    <description>Difference in CAHI at baseline compared to supplemental oxygen Delta CAHI1: CAHIoxygen - CAHIbaseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Delta CAHI2</measure>
    <time_frame>2 years</time_frame>
    <description>Difference in CAHI at baseline compared to medical air Delta CAHI2: CAHImedical air - CAHIbaseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in CAHI1 and CAHI2</measure>
    <time_frame>2 years</time_frame>
    <description>A comparison of change in CAHI1 and change in CAHI2 DeltaCAHI1: DeltaCAHI2</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Arousal Index1</measure>
    <time_frame>2 years</time_frame>
    <description>Difference in Arousal Index at baseline compared to medical air Delta Arousal Index: Arousal Indexmedical air - Arousal Indexbaseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arousal Index2</measure>
    <time_frame>2 years</time_frame>
    <description>Difference in Arousal Index at baseline compared to Supplemental oxygen Delta Arousal Index: Arousal Indexoxygen - Arousal Indexbaseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Desaturation Index1</measure>
    <time_frame>2 years</time_frame>
    <description>Difference in Desaturation Index at baseline compared to medical air Delta Arousal Index: Desaturation Indexmedical air - Desaturation Indexbaseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Desaturation Index2</measure>
    <time_frame>2 years</time_frame>
    <description>Difference in Desaturation Index at baseline compared to supplemental oxygen Delta Arousal Index: Desaturation Indexoxygen - Desaturation Indexbaseline</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Sleep Apnea, Central</condition>
  <condition>Prader-Willi Syndrome</condition>
  <arm_group>
    <arm_group_label>Arm A: Medical air followed by oxygen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: Oxygen followed by medical air</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Medical Air vs Oxygen</intervention_name>
    <description>Medical Air/Oxygen will be given</description>
    <arm_group_label>Arm A: Medical air followed by oxygen</arm_group_label>
    <arm_group_label>Arm B: Oxygen followed by medical air</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. infants under age two with genetically confirmed Prader-Willi Syndrome&#xD;
&#xD;
          2. referred to HSC sleep clinic for evaluation with polysomnogram prior to initiation of&#xD;
             growth hormone&#xD;
&#xD;
          3. infants found to have clinically significant central sleep apnea, defined as an&#xD;
             apnea-hypopnea index (AHI) equal to or greater than 5&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. infants delivered prematurely (less than 37 weeks gestational age)&#xD;
&#xD;
          2. term infants with a history of hypoxic-ischemic encephalopathy or stroke&#xD;
&#xD;
          3. any concurrent diagnoses that may cause sleep-disordered breathing (ie. craniofacial&#xD;
             abnormalities, arnold-chiari malformation, etc)&#xD;
&#xD;
          4. infants with a need for daytime supplemental oxygen (ie. cardiac anomalies)&#xD;
&#xD;
          5. infants found to have low baseline oxygen saturations on PSG&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>2 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Reshma Amin, MD</last_name>
      <phone>416-813-6346</phone>
      <phone_ext>206346</phone_ext>
      <email>reshma.amin@sickkids.ca</email>
    </contact>
    <contact_backup>
      <last_name>Munazzah Ambreen</last_name>
      <email>munazzah.ambreen@sickkids.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Reshma Amin, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Suhail Al-Saleh, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Haley Fishman, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Reshma Amin, MD</last_name>
      <phone>416-813-6346</phone>
      <phone_ext>206346</phone_ext>
      <email>reshma.amin@sickkids.ca</email>
    </contact>
    <contact_backup>
      <last_name>Munazzah Ambreen</last_name>
      <email>munazzah.ambreen@sickkids.ca</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>October 24, 2022</last_update_submitted>
  <last_update_submitted_qc>October 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Hospital for Sick Children</investigator_affiliation>
    <investigator_full_name>Reshma Amin</investigator_full_name>
    <investigator_title>Respirologist, Clinician Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Central</mesh_term>
    <mesh_term>Prader-Willi Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03031626
org study id: 1000053577
nct id: NCT03031626
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to determine if treatment with Medical Air (21% oxygen in room air)
      compared to supplemental oxygen (100% oxygen) will lead to similar improvements in the
      central apnea-hypopnea index (CAHI) for infants with Prader-Willi Syndrome.

      Despite the vast amount of research investigating the cause of central sleep apnea, there
      remain gaps in knowledge, lending to further research efforts. The decision to compare oxygen
      to medical air is based on several theorized mechanisms. The first of which is the
      supposition that provision of medical air may act as an arousal stimulus for the
      hypothalamus, thereby preventing sleep disordered breathing. Secondly, the hypercapnic
      challenge performed by Livingston et al demonstrated a delayed hypercapneic arousal response
      in PWS subjects despite simultaneous hyperoxia, leading us to question if therapeutic oxygen
      really plays a significant role in treating CSA. Lastly, the delivery of medical air via
      nasal prongs may provide sufficient arousal to terminate the cycle of events leading to
      central apnea, as described by Urquhart et al.

      A deeper understanding of central sleep apnea is essential to ameliorating its adverse
      sequelae, which include symptoms of ADHD, impaired attention, behavioral problems, and
      academic difficulties.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The screening visit will occur during a regularly scheduled clinic visit. The patients that have consented for the study will all undergo the baseline PSG. Only patients with clinically significant CSA after Visit 1 will undergo randomization and complete Visit 2.
Those who have a CAHI greater or equal to 5 will be randomly assigned to Arm A or Arm B. Randomization will be performed using a computer with random numbers drawn. Arm A will receive Medical Air followed by Oxygen and Arm B will receive Oxygen followed by Medical Air.
primary purpose: Treatment
masking: Triple (Care Provider, Investigator, Outcomes Assessor)
masking description: The split-night polysomnograms (Arm A, Arm B) will be scored by a blinded independent sleep technologist. A Sleep Physician will report the sleep study and be blinded as to the gas assignment (ie Arm A or Arm B).
measure: Delta CAHI1
time frame: 2 years
description: Difference in CAHI at baseline compared to supplemental oxygen Delta CAHI1: CAHIoxygen - CAHIbaseline
measure: Delta CAHI2
time frame: 2 years
description: Difference in CAHI at baseline compared to medical air Delta CAHI2: CAHImedical air - CAHIbaseline
measure: Difference in CAHI1 and CAHI2
time frame: 2 years
description: A comparison of change in CAHI1 and change in CAHI2 DeltaCAHI1: DeltaCAHI2
measure: Arousal Index1
time frame: 2 years
description: Difference in Arousal Index at baseline compared to medical air Delta Arousal Index: Arousal Indexmedical air - Arousal Indexbaseline
measure: Arousal Index2
time frame: 2 years
description: Difference in Arousal Index at baseline compared to Supplemental oxygen Delta Arousal Index: Arousal Indexoxygen - Arousal Indexbaseline
measure: Desaturation Index1
time frame: 2 years
description: Difference in Desaturation Index at baseline compared to medical air Delta Arousal Index: Desaturation Indexmedical air - Desaturation Indexbaseline
measure: Desaturation Index2
time frame: 2 years
description: Difference in Desaturation Index at baseline compared to supplemental oxygen Delta Arousal Index: Desaturation Indexoxygen - Desaturation Indexbaseline
arm group label: Arm A: Medical air followed by oxygen
arm group type: Experimental
arm group label: Arm B: Oxygen followed by medical air
arm group type: Experimental
intervention type: Biological
intervention name: Medical Air vs Oxygen
description: Medical Air/Oxygen will be given
arm group label: Arm A: Medical air followed by oxygen
arm group label: Arm B: Oxygen followed by medical air
criteria: 
gender: All
minimum age: N/A
maximum age: 2 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: The Hospital for Sick Children
investigator full name: Reshma Amin
investigator title: Respirologist, Clinician Investigator
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Central
mesh term: Prader-Willi Syndrome
mesh term: Syndrome
sharing ipd: Undecided