<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/NCT03287973</url>
  </required_header>
  <id_info>
    <org_study_id>OSA-Craniofacial study</org_study_id>
    <nct_id>NCT03287973</nct_id>
  </id_info>
  <brief_title>Effect of Weight Loss and CPAP on OSA and Metabolic Profile Stratified by Craniofacial Phenotype</brief_title>
  <official_title>Effect of Weight Loss and CPAP on OSA and Metabolic Profile Stratified by Craniofacial Phenotype</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese University of Hong Kong</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>
      Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing (SDB). Weight&#xD;
      reduction has always been advocated in patients with OSA who are overweight and may lead to&#xD;
      improvement in the severity of OSA. Previous study reported a randomized controlled trial of&#xD;
      dietician-led lifestyle modification program (LMP) in 104 patients and found that LMP group&#xD;
      had significantly more weight loss and reduced OSA severity, and the response was sustained&#xD;
      after 8 months.&#xD;
&#xD;
      This study is aimed to compare the effect of weight loss or CPAP alone on subclinical&#xD;
      inflammation, insulin resistance and blood pressure in patients with obesity and&#xD;
      moderate-to-severe obstructive sleep apnea, stratified according to the degree of&#xD;
      craniofacial restriction.&#xD;
&#xD;
      The study plans to recruit consecutive patients who have been referred to the Respiratory&#xD;
      Clinic at the Prince of Wales Hospital with clinical suspicion of sleep-disordered breathing&#xD;
      with specific study entry criteria including an age of 18 or more, body mass index (BMI) &gt;25&#xD;
      kg/m2, and moderate to severe OSA diagnosed by home sleep study. Patients having conditions&#xD;
      that will affect the serum level of hsCRP will be excluded.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing (SDB). It causes&#xD;
      sleep fragmentation, disabling daytime sleepiness, impaired cognitive function, poor quality&#xD;
      of life and cardiovascular diseases. Weight reduction has always been advocated in patients&#xD;
      with OSA who are overweight and may lead to improvement in the severity of OSA. Previous&#xD;
      study reported a randomized controlled trial of dietician-led lifestyle modification program&#xD;
      (LMP) in 104 patients and found that LMP group had significantly more weight loss and reduced&#xD;
      OSA severity, and the response was sustained after 8 months. However, a wide variety of&#xD;
      response to the therapy was observed with 21.3% of patients with severe disease that&#xD;
      converted to mild to moderate and only 6.6% of those with severe disease who became mild in&#xD;
      severity. Apart from obesity, craniofacial factors are well recognized in the pathogenesis of&#xD;
      OSA and are likely to play an important role in influencing the response to weight loss. For&#xD;
      the same degree of OSA severity, Caucasians were more overweight whereas Chinese exhibited&#xD;
      more craniofacial bony restriction. Recent studies showed that a smaller craniofacial&#xD;
      skeleton is associated with better response from weight loss program in terms of OSA&#xD;
      improvement. With vast majority of studies investigating the cardiometabolic changes after&#xD;
      CPAP or weight loss on patients with OSA, evaluation based on craniofacial restriction, the&#xD;
      key factor in the pathogenesis, is lacking.&#xD;
&#xD;
      This study aimed to compare the effect of weight loss or CPAP alone on subclinical&#xD;
      inflammation, insulin resistance and blood pressure in patients with obesity and&#xD;
      moderate-to-severe obstructive sleep apnea, stratified according to the degree of&#xD;
      craniofacial restriction.&#xD;
&#xD;
      The study plans to recruit consecutive patients who have been referred to the Respiratory&#xD;
      Clinic at the Prince of Wales Hospital with clinical suspicion of sleep-disordered breathing&#xD;
      with specific study entry criteria including an age of 18 or more, body mass index (BMI) &gt;25&#xD;
      kg/m2, and moderate to severe OSA diagnosed by home sleep study. Patients having conditions&#xD;
      that will affect the serum level of hsCRP will be excluded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">August 31, 2020</completion_date>
  <primary_completion_date type="Actual">August 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The research assistant who scores the sleep study and the laboratory technician who does the blood test are blinded to the intervention arm.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>changes in hsCRP</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>change in Epworth Sleepiness Scale (ESS)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of insulin sensitivity by Matsuda index</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of facial measurements on photography</measure>
    <time_frame>6 months</time_frame>
    <description>Frontal and profile digital photographs of the head and neck are obtained with a standardized setup. A digital camera is mounted on a tripod at a distance of 160 cm from the subject alignment plane.&#xD;
Subjects are photographed standing upright while assuming the natural head position. Standardized methods are used to align subjects for the photographs. For the frontal photograph, the subject's facial landmark nasion is aligned along the subject alignment plane while ensuring both ears are seen equally from the front. For the profile photograph, the subject is instructed to turn 90 degrees to the left after the frontal photograph was taken.&#xD;
The subject's mid-sagittal plane is aligned to the subject alignment plane. Using image analysis software (Image J v1.36, NIH, Bethesda, MD), the photographs are examined for landmark digitization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of anatomic measurements of upper airway on computed tomography imaging</measure>
    <time_frame>6 months</time_frame>
    <description>All subjects will perform a three-dimensional (3D) computed tomography (CT) scans of the head/neck region to evaluate the size of the maxillomandibular volume (MMV) based on the mandibular cephalometric landmarks (left and right condylion, left and right gonion, and menton). All measurements will be made by a single assessor and the analysis will be performed blind to knowledge of AHI data.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">194</enrollment>
  <condition>Obstructive Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>Lifestyle modification program group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with apnea-hypopnea index (AHI) ≥ 15/hr on home sleep study will participate in a dietitian-led lifestyle modification program (LMP) for 6 months. Patients will attend dietary consultation weekly in the first 4 months, and then monthly in the following two months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CPAP group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients randomized into the continuous positive airway pressure (CPAP) group in each arm will be interviewed by the physician on duty and invited to start autoCPAP treatment for 6 months. They will be offered a CPAP education package. Patients will then commence autoCPAP treatment for 6 months at home.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Lifestyle modification</intervention_name>
    <description>A caloric reduction of 10-20% in daily energy intake from the patient's usual diet (i.e. a deficit ≥ 200 calories per day) will be set as the general initial goal, which will be adjusted subsequently based on changes in body weight with target body mass index (BMI) towards 23 kg/m2.</description>
    <arm_group_label>Lifestyle modification program group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Continuous positive airway pressure (CPAP)</intervention_name>
    <description>Patients randomized into the continuous positive airway pressure (CPAP) group in each arm will be interviewed by the physician on duty and invited to start autoCPAP treatment for 6 months. They will be offered a CPAP education package. Patients will then commence autoCPAP treatment for 6 months at home.</description>
    <arm_group_label>CPAP group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with moderate or severe obstructive sleep apnea ( apnea hypopnea&#xD;
             index (AHI) ≥ 15); body mass index ≥25 kg/m2; age 18-70 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Predominant central sleep apnea; conditions that will affect the level of hsCRP;&#xD;
             unstable cardiovascular disease (e.g. recent unstable angina, myocardial infarction,&#xD;
             stroke or transient ischemic attack within the previous 6 months or severe left&#xD;
             ventricular failure; neuromuscular disease affecting or potentially affecting&#xD;
             respiratory muscles; moderate to severe respiratory disease (i.e. breathlessness&#xD;
             affecting activities of daily living) or documented hypoxemia or awake SaO2 &lt;92%);&#xD;
             psychiatric disease that limits the ability to give informed consent or complete the&#xD;
             study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susanna SS Ng, MBChB</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese University of Hong Kong</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Susanna Ng, MBChB</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese University of Hong Kong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chinese University of Hong</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <last_update_submitted>February 11, 2021</last_update_submitted>
  <last_update_submitted_qc>February 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Susanna SS Ng</investigator_full_name>
    <investigator_title>Honorary assistant professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
    <mesh_term>Weight Loss</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/NCT03287973
org study id: OSA-Craniofacial study
nct id: NCT03287973
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing (SDB). Weight
      reduction has always been advocated in patients with OSA who are overweight and may lead to
      improvement in the severity of OSA. Previous study reported a randomized controlled trial of
      dietician-led lifestyle modification program (LMP) in 104 patients and found that LMP group
      had significantly more weight loss and reduced OSA severity, and the response was sustained
      after 8 months.

      This study is aimed to compare the effect of weight loss or CPAP alone on subclinical
      inflammation, insulin resistance and blood pressure in patients with obesity and
      moderate-to-severe obstructive sleep apnea, stratified according to the degree of
      craniofacial restriction.

      The study plans to recruit consecutive patients who have been referred to the Respiratory
      Clinic at the Prince of Wales Hospital with clinical suspicion of sleep-disordered breathing
      with specific study entry criteria including an age of 18 or more, body mass index (BMI) >25
      kg/m2, and moderate to severe OSA diagnosed by home sleep study. Patients having conditions
      that will affect the serum level of hsCRP will be excluded.
Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing (SDB). It causes
      sleep fragmentation, disabling daytime sleepiness, impaired cognitive function, poor quality
      of life and cardiovascular diseases. Weight reduction has always been advocated in patients
      with OSA who are overweight and may lead to improvement in the severity of OSA. Previous
      study reported a randomized controlled trial of dietician-led lifestyle modification program
      (LMP) in 104 patients and found that LMP group had significantly more weight loss and reduced
      OSA severity, and the response was sustained after 8 months. However, a wide variety of
      response to the therapy was observed with 21.3% of patients with severe disease that
      converted to mild to moderate and only 6.6% of those with severe disease who became mild in
      severity. Apart from obesity, craniofacial factors are well recognized in the pathogenesis of
      OSA and are likely to play an important role in influencing the response to weight loss. For
      the same degree of OSA severity, Caucasians were more overweight whereas Chinese exhibited
      more craniofacial bony restriction. Recent studies showed that a smaller craniofacial
      skeleton is associated with better response from weight loss program in terms of OSA
      improvement. With vast majority of studies investigating the cardiometabolic changes after
      CPAP or weight loss on patients with OSA, evaluation based on craniofacial restriction, the
      key factor in the pathogenesis, is lacking.

      This study aimed to compare the effect of weight loss or CPAP alone on subclinical
      inflammation, insulin resistance and blood pressure in patients with obesity and
      moderate-to-severe obstructive sleep apnea, stratified according to the degree of
      craniofacial restriction.

      The study plans to recruit consecutive patients who have been referred to the Respiratory
      Clinic at the Prince of Wales Hospital with clinical suspicion of sleep-disordered breathing
      with specific study entry criteria including an age of 18 or more, body mass index (BMI) >25
      kg/m2, and moderate to severe OSA diagnosed by home sleep study. Patients having conditions
      that will affect the serum level of hsCRP will be excluded.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The research assistant who scores the sleep study and the laboratory technician who does the blood test are blinded to the intervention arm.
measure: changes in hsCRP
time frame: 6 months
measure: change in Epworth Sleepiness Scale (ESS)
time frame: 6 months
measure: Change of insulin sensitivity by Matsuda index
time frame: 6 months
measure: Change of facial measurements on photography
time frame: 6 months
description: Frontal and profile digital photographs of the head and neck are obtained with a standardized setup. A digital camera is mounted on a tripod at a distance of 160 cm from the subject alignment plane.
Subjects are photographed standing upright while assuming the natural head position. Standardized methods are used to align subjects for the photographs. For the frontal photograph, the subject's facial landmark nasion is aligned along the subject alignment plane while ensuring both ears are seen equally from the front. For the profile photograph, the subject is instructed to turn 90 degrees to the left after the frontal photograph was taken.
The subject's mid-sagittal plane is aligned to the subject alignment plane. Using image analysis software (Image J v1.36, NIH, Bethesda, MD), the photographs are examined for landmark digitization.
measure: Change of anatomic measurements of upper airway on computed tomography imaging
time frame: 6 months
description: All subjects will perform a three-dimensional (3D) computed tomography (CT) scans of the head/neck region to evaluate the size of the maxillomandibular volume (MMV) based on the mandibular cephalometric landmarks (left and right condylion, left and right gonion, and menton). All measurements will be made by a single assessor and the analysis will be performed blind to knowledge of AHI data.
arm group label: Lifestyle modification program group
arm group type: Active Comparator
description: Patients with apnea-hypopnea index (AHI) ≥ 15/hr on home sleep study will participate in a dietitian-led lifestyle modification program (LMP) for 6 months. Patients will attend dietary consultation weekly in the first 4 months, and then monthly in the following two months.
arm group label: CPAP group
arm group type: Other
description: Patients randomized into the continuous positive airway pressure (CPAP) group in each arm will be interviewed by the physician on duty and invited to start autoCPAP treatment for 6 months. They will be offered a CPAP education package. Patients will then commence autoCPAP treatment for 6 months at home.
intervention type: Behavioral
intervention name: Lifestyle modification
description: A caloric reduction of 10-20% in daily energy intake from the patient's usual diet (i.e. a deficit ≥ 200 calories per day) will be set as the general initial goal, which will be adjusted subsequently based on changes in body weight with target body mass index (BMI) towards 23 kg/m2.
arm group label: Lifestyle modification program group
intervention type: Device
intervention name: Continuous positive airway pressure (CPAP)
description: Patients randomized into the continuous positive airway pressure (CPAP) group in each arm will be interviewed by the physician on duty and invited to start autoCPAP treatment for 6 months. They will be offered a CPAP education package. Patients will then commence autoCPAP treatment for 6 months at home.
arm group label: CPAP group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Susanna SS Ng, MBChB
role: Principal Investigator
affiliation: Chinese University of Hong Kong
last name: Susanna Ng, MBChB
role: Principal Investigator
affiliation: Chinese University of Hong Kong
facility: 
country: Hong Kong
responsible party type: Principal Investigator
investigator affiliation: Chinese University of Hong Kong
investigator full name: Susanna SS Ng
investigator title: Honorary assistant professor
mesh term: Sleep Apnea, Obstructive
mesh term: Weight Loss
sharing ipd: No