<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/NCT01712269</url>
  </required_header>
  <id_info>
    <org_study_id>BWH-2011P002188</org_study_id>
    <secondary_id>5K24HL093218</secondary_id>
    <nct_id>NCT01712269</nct_id>
  </id_info>
  <brief_title>Assessment of Sleep Apnea and Its Causes Before and After Weight Loss Surgery</brief_title>
  <official_title>Understanding the Role Obesity Plays in the Pathogenesis of Obstructive Sleep Apnea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The central aim of this research project is to determine how the ever-growing problem of&#xD;
      obesity in the western world contributes to the pathophysiology of obstructive sleep apnea&#xD;
      (OSA). To complete this aim, the investigators will determine the impact of obesity on the&#xD;
      mechanisms underlying OSA. This will be achieved by making physiological measurements of 4&#xD;
      physiological traits known to cause OSA as well as the patients sleep apnea severity, before&#xD;
      and after weight-loss surgery (i.e. bariatric surgery).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obstructive sleep apnea (OSA) is characterized by repetitive collapse or 'obstruction' of the&#xD;
      pharyngeal airway during sleep. These obstructions result in repetitive hypopneas/apneas and&#xD;
      cause intermittent hypoxia/hypercapnia, as well as surges in sympathetic activity. Such&#xD;
      processes disturb normal sleep and impair neurocognitive function, often resulting in&#xD;
      excessive daytime sleepiness and decreased quality of life. Furthermore, OSA is associated&#xD;
      with cardiovascular morbidity and mortality, making OSA a major health concern. Obesity is&#xD;
      categorically the major risk factor for OSA, with available data indicating a prevalence of&#xD;
      40% in obese men (BMI &gt; 30kg/m2) and up to 90% in morbidly obese individuals (BMI &gt; 40kg/m2).&#xD;
      Given the prevalence of obesity has risen to epidemic proportions, with approximately 60% of&#xD;
      adults considered overweight and 30% obese, it has become one of the world's leading health&#xD;
      care concerns and research priorities. Importantly, as the prevalence of obesity continues to&#xD;
      rise, so too does the number of individuals developing OSA. Surprisingly, despite the&#xD;
      dominant role played by obesity in OSA pathogenesis, the precise mechanisms by which obesity&#xD;
      leads to OSA are unclear&#xD;
&#xD;
      Current evidence suggests that OSA pathogenesis involves the interactions of at least four&#xD;
      physiological traits comprising 1) the pharyngeal anatomy and its propensity towards collapse&#xD;
      2) the ability of the upper airway dilator muscles to activate and reopen the airway during&#xD;
      sleep (i.e. neuromuscular compensation), 3) the arousal threshold from sleep (i.e. the&#xD;
      propensity for hypopneas/apneas to lead to arousal and fragmented sleep) and 4) the stability&#xD;
      of ventilatory feedback loop (i.e. loop gain). The potential mechanisms by which obesity may&#xD;
      alter the four traits has to date not been carefully assessed. Specifically, obesity has been&#xD;
      suggested to a) compromise the anatomy by decreasing the airway size and increasing its&#xD;
      collapsibility, but it may also b) impair neuromuscular compensation by increasing the&#xD;
      mechanical load placed on the upper airway muscles, c) increase the loop gain and destabilize&#xD;
      breathing potentially via reductions in lung volume and increased chemosensitivity or d)&#xD;
      increase the arousal threshold and thereby reduce the propensity to arouse from sleep which&#xD;
      may offset some of the obesity-related deficits in the other traits. However, we do not know&#xD;
      how obesity alters these four traits (in the same individual) and whether it involves&#xD;
      predominantly one or several of the mechanistic pathways.&#xD;
&#xD;
      Therefore the aim of our study is to determine the impact of obesity on the mechanisms&#xD;
      underlying OSA. This will be achieved by making physiological measurements before and after&#xD;
      weight-loss surgery (i.e. bariatric surgery). Specifically we will assess:&#xD;
&#xD;
        1. The severity of OSA (apnea-hypopnea-index or AHI)&#xD;
&#xD;
        2. The physiological traits responsible for OSA:&#xD;
&#xD;
      i. Pharyngeal anatomy and its propensity towards collapse&#xD;
&#xD;
      ii. The ability of the upper airway dilator muscles to activate and reopen the airway during&#xD;
      sleep (i.e. neuromuscular compensation).&#xD;
&#xD;
      iii. Arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to&#xD;
      arousal and fragmented sleep).&#xD;
&#xD;
      iv. Stability of ventilatory feedback loop (i.e. loop gain).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    PI and main Co-I (Dr Edwards) relocated locations&#xD;
  </why_stopped>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Model prediction of absence/presence of OSA</measure>
    <time_frame>Subjects will be assessed at baseline (pre-surgery)</time_frame>
    <description>Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which CPAP is dropped from an optimum to various suboptimum pressures during sleep. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Model prediction of absence/presence of OSA</measure>
    <time_frame>Subjects will be assessed between 9-12 months post surgery</time_frame>
    <description>Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which CPAP is dropped from an optimum to various suboptimum pressures during sleep. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Apnea-Hypopnea Index</measure>
    <time_frame>Subjects will be assessed at baseline (pre-surgery)</time_frame>
    <description>The Apnea-Hypopnea Index (AHI) is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apnea-Hypopnea Index</measure>
    <time_frame>Subjects will be assessed between 9-12 months post surgery</time_frame>
    <description>The Apnea-Hypopnea Index (AHI) is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Sleep Apnea, Obstructive</condition>
  <arm_group>
    <arm_group_label>Weight-loss (bariatric) surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects enrolled will undergo bariatric surgery to assist weight-loss</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Weight-loss (bariatric) surgery</intervention_name>
    <description>Subjects will undergo bariatric surgery which will assist weight loss</description>
    <arm_group_label>Weight-loss (bariatric) surgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages 18 - 65 years&#xD;
&#xD;
          -  BMI &gt; 35kg/m2&#xD;
&#xD;
          -  Scheduled for weight-loss surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous history of bariatric surgery&#xD;
&#xD;
          -  Any serious medical condition (except controlled hypertension and diabetes)&#xD;
&#xD;
          -  Any sleep disorder except OSA (RLS, insomnia, etc.)&#xD;
&#xD;
          -  Use of medications known to affect sleep/arousal, breathing, or muscle physiology&#xD;
&#xD;
          -  Allergy to lidocaine or Afrin&#xD;
&#xD;
          -  History of current cigarette smoking or previous smoking history &gt;10 pack years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Atul Malhotra, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham &amp; Womens Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 23, 2012</study_first_posted>
  <last_update_submitted>February 28, 2017</last_update_submitted>
  <last_update_submitted_qc>February 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Atul Malhotra, MD</investigator_full_name>
    <investigator_title>Associate 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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT01712269
org study id: BWH-2011P002188
secondary id: 5K24HL093218
nct id: NCT01712269
lead sponsor: 
collaborator: 
has dmc: No
The central aim of this research project is to determine how the ever-growing problem of
      obesity in the western world contributes to the pathophysiology of obstructive sleep apnea
      (OSA). To complete this aim, the investigators will determine the impact of obesity on the
      mechanisms underlying OSA. This will be achieved by making physiological measurements of 4
      physiological traits known to cause OSA as well as the patients sleep apnea severity, before
      and after weight-loss surgery (i.e. bariatric surgery).
Obstructive sleep apnea (OSA) is characterized by repetitive collapse or 'obstruction' of the
      pharyngeal airway during sleep. These obstructions result in repetitive hypopneas/apneas and
      cause intermittent hypoxia/hypercapnia, as well as surges in sympathetic activity. Such
      processes disturb normal sleep and impair neurocognitive function, often resulting in
      excessive daytime sleepiness and decreased quality of life. Furthermore, OSA is associated
      with cardiovascular morbidity and mortality, making OSA a major health concern. Obesity is
      categorically the major risk factor for OSA, with available data indicating a prevalence of
      40% in obese men (BMI > 30kg/m2) and up to 90% in morbidly obese individuals (BMI > 40kg/m2).
      Given the prevalence of obesity has risen to epidemic proportions, with approximately 60% of
      adults considered overweight and 30% obese, it has become one of the world's leading health
      care concerns and research priorities. Importantly, as the prevalence of obesity continues to
      rise, so too does the number of individuals developing OSA. Surprisingly, despite the
      dominant role played by obesity in OSA pathogenesis, the precise mechanisms by which obesity
      leads to OSA are unclear

      Current evidence suggests that OSA pathogenesis involves the interactions of at least four
      physiological traits comprising 1) the pharyngeal anatomy and its propensity towards collapse
      2) the ability of the upper airway dilator muscles to activate and reopen the airway during
      sleep (i.e. neuromuscular compensation), 3) the arousal threshold from sleep (i.e. the
      propensity for hypopneas/apneas to lead to arousal and fragmented sleep) and 4) the stability
      of ventilatory feedback loop (i.e. loop gain). The potential mechanisms by which obesity may
      alter the four traits has to date not been carefully assessed. Specifically, obesity has been
      suggested to a) compromise the anatomy by decreasing the airway size and increasing its
      collapsibility, but it may also b) impair neuromuscular compensation by increasing the
      mechanical load placed on the upper airway muscles, c) increase the loop gain and destabilize
      breathing potentially via reductions in lung volume and increased chemosensitivity or d)
      increase the arousal threshold and thereby reduce the propensity to arouse from sleep which
      may offset some of the obesity-related deficits in the other traits. However, we do not know
      how obesity alters these four traits (in the same individual) and whether it involves
      predominantly one or several of the mechanistic pathways.

      Therefore the aim of our study is to determine the impact of obesity on the mechanisms
      underlying OSA. This will be achieved by making physiological measurements before and after
      weight-loss surgery (i.e. bariatric surgery). Specifically we will assess:

        1. The severity of OSA (apnea-hypopnea-index or AHI)

        2. The physiological traits responsible for OSA:

      i. Pharyngeal anatomy and its propensity towards collapse

      ii. The ability of the upper airway dilator muscles to activate and reopen the airway during
      sleep (i.e. neuromuscular compensation).

      iii. Arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to
      arousal and fragmented sleep).

      iv. Stability of ventilatory feedback loop (i.e. loop gain).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Model prediction of absence/presence of OSA
time frame: Subjects will be assessed at baseline (pre-surgery)
description: Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which CPAP is dropped from an optimum to various suboptimum pressures during sleep. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence.
measure: Model prediction of absence/presence of OSA
time frame: Subjects will be assessed between 9-12 months post surgery
description: Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which CPAP is dropped from an optimum to various suboptimum pressures during sleep. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence.
measure: Apnea-Hypopnea Index
time frame: Subjects will be assessed at baseline (pre-surgery)
description: The Apnea-Hypopnea Index (AHI) is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow)
measure: Apnea-Hypopnea Index
time frame: Subjects will be assessed between 9-12 months post surgery
description: The Apnea-Hypopnea Index (AHI) is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow)
arm group label: Weight-loss (bariatric) surgery
arm group type: Experimental
description: All subjects enrolled will undergo bariatric surgery to assist weight-loss
intervention type: Procedure
intervention name: Weight-loss (bariatric) surgery
description: Subjects will undergo bariatric surgery which will assist weight loss
arm group label: Weight-loss (bariatric) surgery
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Atul Malhotra, MD
role: Principal Investigator
affiliation: Brigham & Womens Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Atul Malhotra, MD
investigator title: Associate Professor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
sharing ipd: No