<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/NCT02967536</url>
  </required_header>
  <id_info>
    <org_study_id>170912</org_study_id>
    <nct_id>NCT02967536</nct_id>
  </id_info>
  <brief_title>Investigating the Neuropathology of Obstructive Sleep Apnoea</brief_title>
  <acronym>INcOSA</acronym>
  <official_title>Investigating the Neuropathology of Obstructive Sleep Apnoea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>King's College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Our multi-disciplinary research group works closely with people who have obstructive sleep&#xD;
      apnoea. This is a life-long illness that causes breathing to stop during sleep, which leads&#xD;
      to low-oxygen in the blood. Breathing restarts when the airway at the back of the throat&#xD;
      reopens, usually during arousal from sleep. In some people the repeated arousals from sleep&#xD;
      cause daytime sleepiness. Our research has shown that the low blood oxygen levels affect&#xD;
      thinking and feeling, and in some cases we think it damages the brain cells involved with&#xD;
      memory, attention, emotions and decision-making.&#xD;
&#xD;
      This study will investigate the relationship between the amount of oxygen in the blood and&#xD;
      the loss (if any) of brain cells. Also how the ability to perform complex tasks is affected&#xD;
      in patients that suffer from sleep apnoea. The results will show whether the brain damage in&#xD;
      patients with sleep apnoea can be reversed with treatment. These findings will guide doctors&#xD;
      in the treatment for sleep apnoea and they will cast light onto the process of memory decline&#xD;
      with the aim to preserve brain function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a cross-sectional physiological study, which is anticipated to last for 4 years. In&#xD;
      order to study the mechanism of cognitive dysfunction in Obstructive Sleep Apnoea (OSA),&#xD;
      patients will start Continuous Positive Airway Pressure (CPAP) treatment following the&#xD;
      confirmed diagnosis of sleep apnoea. CPAP is the treatment of choice for patients with&#xD;
      moderate to severe OSA who are sleepy during the day. It is also used in patients with mild&#xD;
      OSA if they are excessively sleepy or suffer from cardiovascular risk factors. It is&#xD;
      recommended by the National Institute for Clinical Excellence (NICE) as a treatment for&#xD;
      adults with moderate or severe OSA (Sleep apnoea - continuous positive airway pressure, NICE&#xD;
      2008). In the proposed study the initiation of CPAP will be within the 18 week period set out&#xD;
      in the National Health Service (NHS) Improvement Plan and Standards for Better Health&#xD;
      (Standards for Better Health, Department of Health 2004). No patient with a diagnosis of OSA&#xD;
      will commence treatment with CPAP later than advised by the NICE guidelines of clinical&#xD;
      judgement for the best interest of the patient.&#xD;
&#xD;
      In order to investigate the neuroinflammation process and discrete changes in the brain of&#xD;
      patients with OSA, a minimum of 9 patients with mild OSA and 9 patients with severe OSA will&#xD;
      be compared to 9 healthy controls following initial sleep (assessment) study. All&#xD;
      participants will undergo a dynamic Positron Emission Tomography with Magnetic Resonance&#xD;
      Imaging (PET-MR) scan with the Translocator protein (TSPO) tracer [Fluorine-18]&#xD;
      N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide&#xD;
      (DPA-714) at the time of enrolment to the study. Each participant will also have an MRI scan&#xD;
      and cognitive testing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2017</start_date>
  <completion_date type="Actual">September 9, 2019</completion_date>
  <primary_completion_date type="Actual">September 9, 2019</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Levels of neuroinflammation, brain morphology and neurophysiology will be measured via MRI, PET-MRI imaging &amp; EEG.</measure>
    <time_frame>MRI, PET-MRI &amp; EEG data analyses will begin right after the completion of data collection, and the summary of results will be reported as soon as available, expected before the completion date of the study as per IRAS 01/06/2020.</time_frame>
    <description>27 participants, 9 healthy controls, 9 mild patients &amp; 9 severe patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cognitive performance using the CANTAB battery.</measure>
    <time_frame>Cognitive performance data analyses will be conducted after the completion of data collection, and the summary of results will be reported along the rest of results in the summary that will be published before 01/06/2020.</time_frame>
    <description>27 participants, 9 healthy controls, 9 mild patients &amp; 9 severe patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Genetic analysis and linkage to clinical and neuroimaging data will be measured using biological samples (blood or saliva) analysed and stored in the BioResource for Mental and Neurological Health.</measure>
    <time_frame>Genetic analysis and linkage to clinical and neuroimaging data analyses are expected to continue after the end of the primary study and they will be independently reported by the BioResource for Mental and Neurological Health KCL, within 5 years of study</time_frame>
    <description>18 patients, 9 mild &amp; 9 severe.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">27</enrollment>
  <condition>Obstructive Sleep Apnoea</condition>
  <condition>Inflammation</condition>
  <arm_group>
    <arm_group_label>Mild OSA</arm_group_label>
    <description>Untreated OSA patients. Apnoea-Hypopnoea Index (AHI) &gt;5 events/hour and &lt;10 events/hour with Epworth Sleepiness Score (ESS)&gt;9.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Severe OSA</arm_group_label>
    <description>Untreated OSA patients. AHI &gt;30 events/hour, with excessive sleepiness (ESS &gt;9).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy control</arm_group_label>
    <description>Healthy control. AHI &lt;5 events/hour.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Participants will be invited to donate samples (blood or saliva) to the Biomedical Research&#xD;
      Centre (BRC) Bioresource. In order to have statistical power for genetic analysis, samples&#xD;
      from INcOSA participants will need to be combined with those from the OSA BioResource&#xD;
      (Research Tissue Bank) volunteers who have provided consented biological samples for future&#xD;
      research.&#xD;
&#xD;
      These samples may be used for genetic, epigenetic, metabolomic or proteomic analysis.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patient group:&#xD;
&#xD;
          -  Untreated patients with mild Sleep Apnoea - Apnoea-Hypopnoea Index (AHI) &gt;5&#xD;
             events/hour and &lt;10 events/hour with excessive sleepiness (Epworth sleepiness score&#xD;
             &gt;9).&#xD;
&#xD;
          -  Untreated patients with severe Sleep Apnoea - AHI &gt;30 events/hour with excessive&#xD;
             sleepiness (Epworth sleepiness score &gt;9).&#xD;
&#xD;
        Healthy control group:&#xD;
&#xD;
          -  Male participants&#xD;
&#xD;
          -  No history of sleep disorders&#xD;
&#xD;
          -  AHI≤5/hour&#xD;
&#xD;
          -  No current or previous major neurological or psychiatric disease&#xD;
&#xD;
          -  Not currently undertaking neuropharmacological treatment&#xD;
&#xD;
          -  Non-smoker&#xD;
&#xD;
          -  No history of alcohol or recreational drug abuse, major organ failure&#xD;
&#xD;
          -  Not professional drivers or shift workers.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
        Participants with OSA:&#xD;
&#xD;
          -  Male patients&#xD;
&#xD;
          -  With untreated OSA either mild (AHI≥5/hour and ≤10/hour)&#xD;
&#xD;
          -  or severe (AHI≥30/hour)&#xD;
&#xD;
          -  With excessive sleepiness (ESS≥9)&#xD;
&#xD;
          -  Aged 18-69 years&#xD;
&#xD;
        Healthy control group:&#xD;
&#xD;
          -  Male participants&#xD;
&#xD;
          -  No history of sleep disorders&#xD;
&#xD;
          -  AHI≤5/hour&#xD;
&#xD;
          -  No current or previous major neurological or psychiatric disease&#xD;
&#xD;
          -  Not currently undertaking neuropharmacological treatment&#xD;
&#xD;
          -  Non-smoker&#xD;
&#xD;
          -  No history of alcohol or recreational drug abuse&#xD;
&#xD;
          -  No major organ failure&#xD;
&#xD;
          -  Not professional drivers or shift workers&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Having other sleep disorders, neurological or psychiatric disease&#xD;
&#xD;
          -  Undertaking neuropharmacological treatment&#xD;
&#xD;
          -  Has a history of alcohol or recreational drug abuse, major organ failure&#xD;
&#xD;
          -  Professional drivers or shift workers&#xD;
&#xD;
          -  Unable to have MR scan (e.g. too heavy (&gt;200Kg) or have ferromagnetic implants)&#xD;
&#xD;
          -  [18F]DPA-714 affinity too low&#xD;
&#xD;
          -  Inability to comprehend what is proposed&#xD;
&#xD;
          -  Inability to travel to the research sites&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ivana Rosenzweig, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>King's College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Guy's Hospital Sleep Centre</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 17, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>October 8, 2019</last_update_submitted>
  <last_update_submitted_qc>October 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cognitive function</keyword>
  <keyword>microglia</keyword>
  <keyword>neuroinflammation</keyword>
  <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>Inflammation</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/NCT02967536
org study id: 170912
nct id: NCT02967536
lead sponsor: 
collaborator: 
has dmc: No
Our multi-disciplinary research group works closely with people who have obstructive sleep
      apnoea. This is a life-long illness that causes breathing to stop during sleep, which leads
      to low-oxygen in the blood. Breathing restarts when the airway at the back of the throat
      reopens, usually during arousal from sleep. In some people the repeated arousals from sleep
      cause daytime sleepiness. Our research has shown that the low blood oxygen levels affect
      thinking and feeling, and in some cases we think it damages the brain cells involved with
      memory, attention, emotions and decision-making.

      This study will investigate the relationship between the amount of oxygen in the blood and
      the loss (if any) of brain cells. Also how the ability to perform complex tasks is affected
      in patients that suffer from sleep apnoea. The results will show whether the brain damage in
      patients with sleep apnoea can be reversed with treatment. These findings will guide doctors
      in the treatment for sleep apnoea and they will cast light onto the process of memory decline
      with the aim to preserve brain function.
This is a cross-sectional physiological study, which is anticipated to last for 4 years. In
      order to study the mechanism of cognitive dysfunction in Obstructive Sleep Apnoea (OSA),
      patients will start Continuous Positive Airway Pressure (CPAP) treatment following the
      confirmed diagnosis of sleep apnoea. CPAP is the treatment of choice for patients with
      moderate to severe OSA who are sleepy during the day. It is also used in patients with mild
      OSA if they are excessively sleepy or suffer from cardiovascular risk factors. It is
      recommended by the National Institute for Clinical Excellence (NICE) as a treatment for
      adults with moderate or severe OSA (Sleep apnoea - continuous positive airway pressure, NICE
      2008). In the proposed study the initiation of CPAP will be within the 18 week period set out
      in the National Health Service (NHS) Improvement Plan and Standards for Better Health
      (Standards for Better Health, Department of Health 2004). No patient with a diagnosis of OSA
      will commence treatment with CPAP later than advised by the NICE guidelines of clinical
      judgement for the best interest of the patient.

      In order to investigate the neuroinflammation process and discrete changes in the brain of
      patients with OSA, a minimum of 9 patients with mild OSA and 9 patients with severe OSA will
      be compared to 9 healthy controls following initial sleep (assessment) study. All
      participants will undergo a dynamic Positron Emission Tomography with Magnetic Resonance
      Imaging (PET-MR) scan with the Translocator protein (TSPO) tracer [Fluorine-18]
      N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide
      (DPA-714) at the time of enrolment to the study. Each participant will also have an MRI scan
      and cognitive testing.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Levels of neuroinflammation, brain morphology and neurophysiology will be measured via MRI, PET-MRI imaging & EEG.
time frame: MRI, PET-MRI & EEG data analyses will begin right after the completion of data collection, and the summary of results will be reported as soon as available, expected before the completion date of the study as per IRAS 01/06/2020.
description: 27 participants, 9 healthy controls, 9 mild patients & 9 severe patients.
measure: Cognitive performance using the CANTAB battery.
time frame: Cognitive performance data analyses will be conducted after the completion of data collection, and the summary of results will be reported along the rest of results in the summary that will be published before 01/06/2020.
description: 27 participants, 9 healthy controls, 9 mild patients & 9 severe patients.
measure: Genetic analysis and linkage to clinical and neuroimaging data will be measured using biological samples (blood or saliva) analysed and stored in the BioResource for Mental and Neurological Health.
time frame: Genetic analysis and linkage to clinical and neuroimaging data analyses are expected to continue after the end of the primary study and they will be independently reported by the BioResource for Mental and Neurological Health KCL, within 5 years of study
description: 18 patients, 9 mild & 9 severe.
arm group label: Mild OSA
description: Untreated OSA patients. Apnoea-Hypopnoea Index (AHI) >5 events/hour and <10 events/hour with Epworth Sleepiness Score (ESS)>9.
arm group label: Severe OSA
description: Untreated OSA patients. AHI >30 events/hour, with excessive sleepiness (ESS >9).
arm group label: Healthy control
description: Healthy control. AHI <5 events/hour.
Participants will be invited to donate samples (blood or saliva) to the Biomedical Research
      Centre (BRC) Bioresource. In order to have statistical power for genetic analysis, samples
      from INcOSA participants will need to be combined with those from the OSA BioResource
      (Research Tissue Bank) volunteers who have provided consented biological samples for future
      research.

      These samples may be used for genetic, epigenetic, metabolomic or proteomic analysis.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ivana Rosenzweig, MD, PhD
role: Principal Investigator
affiliation: King's College London
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Inflammation