<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/NCT02264353</url>
  </required_header>
  <id_info>
    <org_study_id>UCSD141272</org_study_id>
    <nct_id>NCT02264353</nct_id>
  </id_info>
  <brief_title>The Impact of Arousal Threshold in Obstructive Sleep Apnea</brief_title>
  <official_title>The Impact of Arousal Threshold in Obstructive Sleep Apnea: Donepezil's Effects on the Arousal Threshold and on the Apnea Hypopnea Index</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Diego</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesis is that obstructive sleep apnea (OSA) patients with a low&#xD;
      arousal threshold may wake up too early during a respiratory event, before upper airway&#xD;
      muscles can be activated to achieve stable ventilation. Thus, strategies to manipulate the&#xD;
      respiratory arousal threshold could potentially improve the quality of sleep and sleep&#xD;
      disordered breathing. Agents that raise arousal threshold are therefore likely to benefit&#xD;
      some patients with OSA. The overall goal of this project is to determine the importance of&#xD;
      the arousal threshold in OSA, determine which patients might benefit from a raised arousal&#xD;
      threshold, and test this hypothesis by using pharmacological manipulation of the arousal&#xD;
      threshold to achieve this goal.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a pilot study. The investigators will test whether donepezil has important&#xD;
      effects on the arousal threshold and on the apnea hypopnea index.&#xD;
&#xD;
      Donepezil is a cholinesterase inhibitor approved by the U.S. Food and Drug Administration&#xD;
      (FDA) for the treatment of symptoms of Alzheimer's disease.&#xD;
&#xD;
      Eligible participants will undergo overnight polysomonography as described below and will&#xD;
      receive either donepezil (10 mg immediately prior to sleep) or placebo (in random order)&#xD;
      followed roughly 14 days later with placebo or donepezil. This aim will allow us to test the&#xD;
      impact of donepezil on the apnea hypopnea index. The study plans to enroll approximately 30&#xD;
      subjects.&#xD;
&#xD;
      The change in apnea hypopnea index as well as arousal thresholds/upper airway mechanics will&#xD;
      be compared in the donepezil groups with the placebo group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Apnea Hypopnea Index (AHI)</measure>
    <time_frame>14 days (during overnight sleep study after donepezil or placebo is given)</time_frame>
    <description>The Apnea-Hypopnea Index or Apnoea-Hypopnoea Index (AHI) is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. The apneas (pauses in breathing) must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A higher AHI value indicates more severe sleep apnea</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Respiratory Arousal Threshold</measure>
    <time_frame>14 days (during overnight sleep study after donepezil or placebo is given)</time_frame>
    <description>Arousal Threshold was measured as the average nadir epiglottic airway pressure immediately before electroencephalogram (EEG) arousal. It was measured with an epiglottic pressure catheter. The epiglottic catheter/balloon is linked in a pressure catheter inserted through the de-congested, anesthetized nostril and the tip of the catheter located at hypopharyngeal area.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Loop Gain</measure>
    <time_frame>14 days (during overnight sleep study after donepezil or placebo is given)</time_frame>
    <description>The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of obstructive sleep apnea (OSA). The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of OSA 21. Loop gain is reflected in the size of the ventilatory overshoot following a ventilatory perturbation (hypopnea/apnea), where loop gain = response/disturbance. Ventilatory fluctuations are estimated using the square-root transformed nasal pressure waveform. Loop gain was reported as the ventilatory response to a 1 cycle/min disturbance (LG1); a value of LGn&gt;1 yields periodic central apnea. Calculations were performed using MATLAB</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Obstructive Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>Donepezil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sleep data with Donepezil given</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Sleep data with Placebo given</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donepezil</intervention_name>
    <description>Donepezil 10mg before sleep</description>
    <arm_group_label>Donepezil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>One piece of placebo before sleep</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages 18-70 years&#xD;
&#xD;
          -  sleep study (with apnea hypopnea index&gt;5)&#xD;
&#xD;
          -  Diagnosis of obstructive sleep apnea&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any known unstable cardiac (apart from treated hypertension), pulmonary (including&#xD;
             asthma), renal, neurologic (including epilepsy), neuromuscular, or hepatic disease.&#xD;
&#xD;
          -  Susceptible to stomach ulcers.&#xD;
&#xD;
          -  Pregnant women or Nursing mothers&#xD;
&#xD;
          -  Using positive airway pressure (PAP) therapy over one week or longer&#xD;
&#xD;
          -  Body weight &lt;55kg&#xD;
&#xD;
          -  History of hypersensitivity to Afrin, Lidocaine and/or Donepezil&#xD;
&#xD;
          -  History of bleeding diathesis and/or gastrointestinal bleeding.&#xD;
&#xD;
          -  Use of any medications that may affect sleep or breathing.&#xD;
&#xD;
          -  A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar&#xD;
             disorder, major depression, panic or anxiety disorders.&#xD;
&#xD;
          -  Substantial cigarette (&gt;5/day), alcohol (&gt;3oz/day) or use of illicit drugs.&#xD;
&#xD;
          -  More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day.&#xD;
&#xD;
          -  Deprived from sleep in the recent one week&#xD;
&#xD;
          -  Desaturations to below 70% lasting greater than 10 seconds in duration per event in&#xD;
             the sleep study (without Oxygen).&#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>Robert Owens, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Diego</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <results_first_submitted>March 2, 2017</results_first_submitted>
  <results_first_submitted_qc>August 6, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 8, 2019</results_first_posted>
  <last_update_submitted>August 6, 2019</last_update_submitted>
  <last_update_submitted_qc>August 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Robert L. Owens</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Obstructive</keyword>
  <keyword>Sleep Apnea</keyword>
  <keyword>Arousal threshold</keyword>
  <keyword>Donepezil</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Donepezil</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Donepezil Then Placebo</title>
          <description>Sleep data with Donepezil given during Visit 1 followed by a 14 day washout period followed by Sleep data with Placebo given during Visit 2&#xD;
Donepezil: Donepezil 10mg before sleep</description>
        </group>
        <group group_id="P2">
          <title>Placebo Then Donepezil</title>
          <description>Sleep data with Placebo given during Visit 1 followed by a 14 day washout period followed by Sleep data with Donepezil given during Visit 2&#xD;
placebo: One piece of placebo before sleep</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>Participants who were randomized to receive either Donepezil 10mg tablet or Placebo tablet (matching Donepezil 10mg) before sleep</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="41"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="51.6" spread="11.1"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Apnea Hypopnea Index (AHI)&gt;5 events/hr; lowest Oxygen Saturation (SaO2)&gt;70%</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Apnea Hypopnea Index (AHI)</title>
        <description>The Apnea-Hypopnea Index or Apnoea-Hypopnoea Index (AHI) is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. The apneas (pauses in breathing) must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A higher AHI value indicates more severe sleep apnea</description>
        <time_frame>14 days (during overnight sleep study after donepezil or placebo is given)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Donepezil</title>
            <description>Sleep data with Donepezil given&#xD;
Donepezil: Donepezil 10mg before sleep</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Sleep data with Placebo given&#xD;
placebo: One piece of placebo before sleep</description>
          </group>
        </group_list>
        <measure>
          <title>Apnea Hypopnea Index (AHI)</title>
          <description>The Apnea-Hypopnea Index or Apnoea-Hypopnoea Index (AHI) is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. The apneas (pauses in breathing) must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A higher AHI value indicates more severe sleep apnea</description>
          <units>events/hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0" spread="23.4"/>
                    <measurement group_id="O2" value="51.8" spread="27.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.576</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Respiratory Arousal Threshold</title>
        <description>Arousal Threshold was measured as the average nadir epiglottic airway pressure immediately before electroencephalogram (EEG) arousal. It was measured with an epiglottic pressure catheter. The epiglottic catheter/balloon is linked in a pressure catheter inserted through the de-congested, anesthetized nostril and the tip of the catheter located at hypopharyngeal area.</description>
        <time_frame>14 days (during overnight sleep study after donepezil or placebo is given)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Donepezil</title>
            <description>Sleep data with Donepezil given&#xD;
Donepezil: Donepezil 10mg before sleep</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Sleep data with Placebo given&#xD;
placebo: One piece of placebo before sleep</description>
          </group>
        </group_list>
        <measure>
          <title>Respiratory Arousal Threshold</title>
          <description>Arousal Threshold was measured as the average nadir epiglottic airway pressure immediately before electroencephalogram (EEG) arousal. It was measured with an epiglottic pressure catheter. The epiglottic catheter/balloon is linked in a pressure catheter inserted through the de-congested, anesthetized nostril and the tip of the catheter located at hypopharyngeal area.</description>
          <units>cm H20</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.0" lower_limit="-27.0" upper_limit="-11.8"/>
                    <measurement group_id="O2" value="-18.9" lower_limit="-27.5" upper_limit="-12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.394</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Loop Gain</title>
        <description>The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of obstructive sleep apnea (OSA). The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of OSA 21. Loop gain is reflected in the size of the ventilatory overshoot following a ventilatory perturbation (hypopnea/apnea), where loop gain = response/disturbance. Ventilatory fluctuations are estimated using the square-root transformed nasal pressure waveform. Loop gain was reported as the ventilatory response to a 1 cycle/min disturbance (LG1); a value of LGn&gt;1 yields periodic central apnea. Calculations were performed using MATLAB</description>
        <time_frame>14 days (during overnight sleep study after donepezil or placebo is given)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Donepezil</title>
            <description>Sleep data with Donepezil given&#xD;
Donepezil: Donepezil 10mg before sleep</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Sleep data with Placebo given&#xD;
placebo: One piece of placebo before sleep</description>
          </group>
        </group_list>
        <measure>
          <title>Loop Gain</title>
          <description>The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of obstructive sleep apnea (OSA). The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of OSA 21. Loop gain is reflected in the size of the ventilatory overshoot following a ventilatory perturbation (hypopnea/apnea), where loop gain = response/disturbance. Ventilatory fluctuations are estimated using the square-root transformed nasal pressure waveform. Loop gain was reported as the ventilatory response to a 1 cycle/min disturbance (LG1); a value of LGn&gt;1 yields periodic central apnea. Calculations were performed using MATLAB</description>
          <units>Unitless</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.55" spread="0.15"/>
                    <measurement group_id="O2" value="0.58" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.089</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Donepezil</title>
          <description>Sleep data with Donepezil given&#xD;
Donepezil: Donepezil 10mg before sleep</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Sleep data with Placebo given&#xD;
placebo: One piece of placebo before sleep</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Heart Burn</sub_title>
                <description>Subject reported &quot;heart burn&quot; and decided to quit after taking placebo.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Difficulty Falling Asleep</sub_title>
                <description>Subject reported difficulty falling asleep in laboratory after taking placebo.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Underlying mechanism(s) of sleep apnea is likely to vary across individuals such that one might predict that an intervention may only be effective in a subset of OSA patients. We did not measure upper airway gain.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Atul Malhotra, MD</name_or_title>
      <organization>University of California, San Diego</organization>
      <phone>(858) 657-6159</phone>
      <email>amalhotra@ucsd.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/NCT02264353
org study id: UCSD141272
nct id: NCT02264353
lead sponsor: 
has dmc: No
The investigators hypothesis is that obstructive sleep apnea (OSA) patients with a low
      arousal threshold may wake up too early during a respiratory event, before upper airway
      muscles can be activated to achieve stable ventilation. Thus, strategies to manipulate the
      respiratory arousal threshold could potentially improve the quality of sleep and sleep
      disordered breathing. Agents that raise arousal threshold are therefore likely to benefit
      some patients with OSA. The overall goal of this project is to determine the importance of
      the arousal threshold in OSA, determine which patients might benefit from a raised arousal
      threshold, and test this hypothesis by using pharmacological manipulation of the arousal
      threshold to achieve this goal.
This study is a pilot study. The investigators will test whether donepezil has important
      effects on the arousal threshold and on the apnea hypopnea index.

      Donepezil is a cholinesterase inhibitor approved by the U.S. Food and Drug Administration
      (FDA) for the treatment of symptoms of Alzheimer's disease.

      Eligible participants will undergo overnight polysomonography as described below and will
      receive either donepezil (10 mg immediately prior to sleep) or placebo (in random order)
      followed roughly 14 days later with placebo or donepezil. This aim will allow us to test the
      impact of donepezil on the apnea hypopnea index. The study plans to enroll approximately 30
      subjects.

      The change in apnea hypopnea index as well as arousal thresholds/upper airway mechanics will
      be compared in the donepezil groups with the placebo group.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Apnea Hypopnea Index (AHI)
time frame: 14 days (during overnight sleep study after donepezil or placebo is given)
description: The Apnea-Hypopnea Index or Apnoea-Hypopnoea Index (AHI) is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. The apneas (pauses in breathing) must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A higher AHI value indicates more severe sleep apnea
measure: Respiratory Arousal Threshold
time frame: 14 days (during overnight sleep study after donepezil or placebo is given)
description: Arousal Threshold was measured as the average nadir epiglottic airway pressure immediately before electroencephalogram (EEG) arousal. It was measured with an epiglottic pressure catheter. The epiglottic catheter/balloon is linked in a pressure catheter inserted through the de-congested, anesthetized nostril and the tip of the catheter located at hypopharyngeal area.
measure: Loop Gain
time frame: 14 days (during overnight sleep study after donepezil or placebo is given)
description: The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of obstructive sleep apnea (OSA). The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of OSA 21. Loop gain is reflected in the size of the ventilatory overshoot following a ventilatory perturbation (hypopnea/apnea), where loop gain = response/disturbance. Ventilatory fluctuations are estimated using the square-root transformed nasal pressure waveform. Loop gain was reported as the ventilatory response to a 1 cycle/min disturbance (LG1); a value of LGn>1 yields periodic central apnea. Calculations were performed using MATLAB
arm group label: Donepezil
arm group type: Experimental
description: Sleep data with Donepezil given
arm group label: Placebo
arm group type: Placebo Comparator
description: Sleep data with Placebo given
intervention type: Drug
intervention name: Donepezil
description: Donepezil 10mg before sleep
arm group label: Donepezil
intervention type: Drug
intervention name: placebo
description: One piece of placebo before sleep
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Robert Owens, M.D.
role: Principal Investigator
affiliation: University of California, San Diego
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Robert L. Owens
investigator title: Assistant Professor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Donepezil
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Underlying mechanism(s) of sleep apnea is likely to vary across individuals such that one might predict that an intervention may only be effective in a subset of OSA patients. We did not measure upper airway gain.
point of contact: 