<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/NCT02192684</url>
  </required_header>
  <id_info>
    <org_study_id>5U01HL108647-04</org_study_id>
    <nct_id>NCT02192684</nct_id>
  </id_info>
  <brief_title>Obesity, Sleep Apnea, and Insulin Resistance</brief_title>
  <official_title>Interfacing Adiposity, Sleep Apnea, and Insulin Resistance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Obstructive sleep apnea (OSA) and type 2 diabetes confer increasing economic, social, and&#xD;
      public health burdens in the United States. That these diseases appear to co-exist and&#xD;
      together increase one's risk of cardiovascular disease renders investigation into their&#xD;
      shared pathophysiology even more urgent. Investigators will assess prevalence of insulin&#xD;
      resistance, a precursor to diabetes, among overweight patients with OSA. Among those at&#xD;
      highest risk of diabetes, investigators will randomize participants to pioglitazone or&#xD;
      placebo to see the efficacy of the intervention on improving OSA, insulin resistance, and/or&#xD;
      insulin secretion. In a separate intervention, investigators will evaluate the&#xD;
      cardiometabolic benefits of continuous positive airway pressure (CPAP) for 12 weeks in&#xD;
      patients with OSA. Investigators will also study subjects from the community without known&#xD;
      sleep apnea, and assess whether insulin-resistant individuals are at risk for sleep apnea&#xD;
      using clinical screening questionnaires.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2010</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">July 2014</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>Other</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Apnea-hypopnea Index (AHI) Outcome Measure in Response to Pioglitazone or Placebo</measure>
    <time_frame>8 weeks</time_frame>
    <description>To evaluate the effects of pioglitazone versus placebo on AHI in patients with OSA.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Insulin Sensitivity</condition>
  <condition>Obstructive Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>pioglitazone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>pioglitazone 45 mg, oral, daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, one pill daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pioglitazone</intervention_name>
    <description>45 mg daily Insulin sensitizing</description>
    <arm_group_label>pioglitazone</arm_group_label>
    <other_name>actos</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Compare with pioglitazone</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy Individuals&#xD;
&#xD;
          -  Age 30-70 years old&#xD;
&#xD;
          -  BMI- 25-40 kg/m2&#xD;
&#xD;
          -  Must meet criteria for obstructive sleep apnea by overnight in-laboratory&#xD;
             polysomnography&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any significant co-morbidities, such as diabetes, active heart, kidney, liver&#xD;
             diseases, or active or history of bladder cancer.&#xD;
&#xD;
          -  Must not have previously received treatment for OSA, including CPAP.&#xD;
&#xD;
          -  Must not be receiving any medications intended for weight loss, or those known to&#xD;
             influence insulin sensitivity.&#xD;
&#xD;
          -  Pregnancy/lactation is also an exclusion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gerald M Reaven, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <results_first_submitted>November 18, 2016</results_first_submitted>
  <results_first_submitted_qc>March 14, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 21, 2017</results_first_posted>
  <last_update_submitted>March 14, 2017</last_update_submitted>
  <last_update_submitted_qc>March 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Gerald M Reaven</investigator_full_name>
    <investigator_title>Professor Emeritus</investigator_title>
  </responsible_party>
  <keyword>obstructive sleep apnea</keyword>
  <keyword>insulin sensitivity</keyword>
  <keyword>cardiovascular risk</keyword>
  <keyword>positive airway pressure therapy</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>Insulin Resistance</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pioglitazone</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment Dates: July 10 2010 - March 2014</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Pioglitazone</title>
          <description>pioglitazone 45 mg, oral, daily&#xD;
Pioglitazone: 45 mg daily Insulin sensitizing</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo, one pill daily&#xD;
placebo: Compare with pioglitazone</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Pioglitazone</title>
          <description>pioglitazone 45 mg, oral, daily&#xD;
Pioglitazone: 45 mg daily Insulin sensitizing</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo, one pill daily&#xD;
placebo: Compare with pioglitazone</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="45"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51" spread="11"/>
                    <measurement group_id="B2" value="50" spread="12"/>
                    <measurement group_id="B3" value="50.5" spread="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Changes in sleep measure</title>
          <description>apnea-hypopnea index (AHI) events per hour</description>
          <units>Apnea-hypopnea index (AHI) events/hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.9" spread="11.9"/>
                    <measurement group_id="B2" value="40.8" spread="12.3"/>
                    <measurement group_id="B3" value="38.9" spread="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Insulin Sensitivity</title>
          <description>Steady-state plasma glucose (mmol/L)</description>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11.9" spread="2.1"/>
                    <measurement group_id="B2" value="12.3" spread="2.0"/>
                    <measurement group_id="B3" value="12.1" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Apnea-hypopnea Index (AHI) Outcome Measure in Response to Pioglitazone or Placebo</title>
        <description>To evaluate the effects of pioglitazone versus placebo on AHI in patients with OSA.</description>
        <time_frame>8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone</title>
            <description>pioglitazone 45 mg, oral, daily&#xD;
Pioglitazone: 45 mg daily Insulin sensitizing</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo, one pill daily&#xD;
placebo: Compare with pioglitazone</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Apnea-hypopnea Index (AHI) Outcome Measure in Response to Pioglitazone or Placebo</title>
          <description>To evaluate the effects of pioglitazone versus placebo on AHI in patients with OSA.</description>
          <units>AHI events/hour</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.8" lower_limit="21" upper_limit="49"/>
                    <measurement group_id="O2" value="34.4" lower_limit="18" upper_limit="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Pioglitazone</title>
          <description>pioglitazone 45 mg, oral, daily&#xD;
Pioglitazone: 45 mg daily Insulin sensitizing</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo, one pill daily&#xD;
placebo: Compare with pioglitazone</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>Other</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>weight gain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Unrecognized adverse effect of pioglitazone could have obviated a beneficial effect of enhanced insulin sensitivity on OSA related sleep measures.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Gerald Reaven</name_or_title>
      <organization>Stanford Universtiy</organization>
      <phone>650-724-3416</phone>
      <email>greaven@stanford.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02192684
org study id: 5U01HL108647-04
nct id: NCT02192684
lead sponsor: 
has dmc: Yes
Obstructive sleep apnea (OSA) and type 2 diabetes confer increasing economic, social, and
      public health burdens in the United States. That these diseases appear to co-exist and
      together increase one's risk of cardiovascular disease renders investigation into their
      shared pathophysiology even more urgent. Investigators will assess prevalence of insulin
      resistance, a precursor to diabetes, among overweight patients with OSA. Among those at
      highest risk of diabetes, investigators will randomize participants to pioglitazone or
      placebo to see the efficacy of the intervention on improving OSA, insulin resistance, and/or
      insulin secretion. In a separate intervention, investigators will evaluate the
      cardiometabolic benefits of continuous positive airway pressure (CPAP) for 12 weeks in
      patients with OSA. Investigators will also study subjects from the community without known
      sleep apnea, and assess whether insulin-resistant individuals are at risk for sleep apnea
      using clinical screening questionnaires.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Participant)
measure: Change in Apnea-hypopnea Index (AHI) Outcome Measure in Response to Pioglitazone or Placebo
time frame: 8 weeks
description: To evaluate the effects of pioglitazone versus placebo on AHI in patients with OSA.
arm group label: pioglitazone
arm group type: Active Comparator
description: pioglitazone 45 mg, oral, daily
arm group label: placebo
arm group type: Placebo Comparator
description: Placebo, one pill daily
intervention type: Drug
intervention name: Pioglitazone
description: 45 mg daily Insulin sensitizing
arm group label: pioglitazone
other name: actos
intervention type: Drug
intervention name: placebo
description: Compare with pioglitazone
arm group label: placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Gerald M Reaven, M.D.
role: Principal Investigator
affiliation: Stanford University
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Gerald M Reaven
investigator title: Professor Emeritus
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Insulin Resistance
mesh term: Hypersensitivity
mesh term: Pioglitazone
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Unrecognized adverse effect of pioglitazone could have obviated a beneficial effect of enhanced insulin sensitivity on OSA related sleep measures.
point of contact: 