<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/NCT03299257</url>
  </required_header>
  <id_info>
    <org_study_id>RES12</org_study_id>
    <nct_id>NCT03299257</nct_id>
  </id_info>
  <brief_title>Donepezil, Residual Excessive Daytime Sleepiness, Obstructive Sleep Apnea</brief_title>
  <official_title>Donepezil for Residual Symptoms in CPAP Treated Obstructive Sleepapnea Patients: A Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Associação Fundo de Incentivo à Pesquisa</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Associação Fundo de Incentivo à Pesquisa</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is a randomized, double-blind, single-center, 30-day study. Patients aged 35-60 years,&#xD;
      with apnea and hypopnea index and respiratory disturbance index normalized with CPAP, and&#xD;
      Epworth Sleepiness Scale&gt; 11. Patients undergo baseline and CPAP titration polysomnography,&#xD;
      liquor and blood collection, Multiple Sleep Latency Test, anxiety and depression and&#xD;
      cognitive assessments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obstructive Sleep Apnea (OSA) is a sleep-disordered breathing characterized by recurrent&#xD;
      episodes of total or partial obstruction of the upper airway during sleep, which can lead to&#xD;
      cognitive, metabolic and cardiovascular consequences. More recently, OSA has been associated&#xD;
      with worsening Alzheimer's disease symptoms. Resolving respiratory events during sleep often&#xD;
      has a beneficial impact on these consequences. However, even after adequate and optimized&#xD;
      treatment with continuous positive airway pressure (CPAP), about 6 to 10% of patients still&#xD;
      remain sleepy. Given the high prevalence of OSA, this percentage represents a large number of&#xD;
      under-treated and at-risk individuals. This residual excessive sleepiness (RES) may be&#xD;
      related to comorbidities and cognitive alterations. Its physiopathology is still unknown. A&#xD;
      few studies have tested modafinil as an adjunct treatment for RES patients. Since a) CPAP is&#xD;
      ineffective in patients with RES; b) previous studies suggest some benefit with wake&#xD;
      promoters; and c) cognitive impairment has also been reported associated with RES; the&#xD;
      hypothesis of the present study is that donepezil improves alertness and cognition in&#xD;
      patients with OSA and RES, evidencing the role of the cholinergic system in the&#xD;
      pathophysiology of RES.&#xD;
&#xD;
      Objective: To evaluate the effects of donepezil on RES in adult patients treated with CPAP.&#xD;
&#xD;
      Thirty-six patients diagnosed with OSA and RES are estimated to be included. Participants&#xD;
      will be treated with CPAP for more than 6 months with a mean use greater than 5 hours per&#xD;
      day. After blood and cerebrospinal fluid collection, patients will be randomized into 2&#xD;
      groups of 30 days of treatment with donepezil or placebo. RES will be evaluated by the&#xD;
      vigilance test and the Epworth Sleepiness Scale.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 6, 2018</start_date>
  <completion_date type="Anticipated">March 2, 2019</completion_date>
  <primary_completion_date type="Anticipated">November 4, 2018</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>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized, parallel groups, 30-day trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>donepezil and placebo will be dispensed to volunteers in similar pills and numbered boxes.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>objective excessive daytime sleepiness</measure>
    <time_frame>40 days</time_frame>
    <description>Maintenance Wakefulness Test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>subjective excessive daytime sleepiness</measure>
    <time_frame>40 days</time_frame>
    <description>Epworth Sleepiness Scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>cognitive improvement (executive functions)</measure>
    <time_frame>40 days</time_frame>
    <description>standard cognitive tests to evaluate executive functions</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>OSA</condition>
  <condition>Sleepiness</condition>
  <arm_group>
    <arm_group_label>donepezil treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>donepezil with 10 mg will be administered for 30 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo treatment</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo with 10 mg placebo will be administered for 30 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>donepezil treatment</intervention_name>
    <description>30-day donepezil treatment</description>
    <arm_group_label>donepezil treatment</arm_group_label>
    <arm_group_label>placebo treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Both gender, Age between 35 and 65 years;&#xD;
&#xD;
          -  Confirmed diagnosis of moderate to severe OSA;&#xD;
&#xD;
          -  Treatment with CPAP for at least six months;&#xD;
&#xD;
          -  Persistent sleepiness with daily CPAP use compliance &gt; 5 hours per night.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Neurological or psychiatric diseases;&#xD;
&#xD;
          -  Chronic use of psychoactive drugs, other sleep disorders than OSA, visual defficiency,&#xD;
             illiteracy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ksdy Maiara Werli, Psy</last_name>
    <phone>+55-11-958491512</phone>
    <email>ksdymaiara@yahoo.com.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dalva Poyares, MD</last_name>
    <phone>+55-11-985937418</phone>
    <email>poyares@unifesp.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Instituto do Sono</name>
      <address>
        <city>Sao Paulo</city>
        <zip>04024-002</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>May 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>June 26, 2018</last_update_submitted>
  <last_update_submitted_qc>June 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Associação Fundo de Incentivo à Pesquisa</investigator_affiliation>
    <investigator_full_name>Dalva Poyares</investigator_full_name>
    <investigator_title>MD Professor</investigator_title>
  </responsible_party>
  <keyword>OSA</keyword>
  <keyword>CPAP</keyword>
  <keyword>sleepiness</keyword>
  <keyword>donepezil</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleepiness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Donepezil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03299257
org study id: RES12
nct id: NCT03299257
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
It is a randomized, double-blind, single-center, 30-day study. Patients aged 35-60 years,
      with apnea and hypopnea index and respiratory disturbance index normalized with CPAP, and
      Epworth Sleepiness Scale> 11. Patients undergo baseline and CPAP titration polysomnography,
      liquor and blood collection, Multiple Sleep Latency Test, anxiety and depression and
      cognitive assessments.
Obstructive Sleep Apnea (OSA) is a sleep-disordered breathing characterized by recurrent
      episodes of total or partial obstruction of the upper airway during sleep, which can lead to
      cognitive, metabolic and cardiovascular consequences. More recently, OSA has been associated
      with worsening Alzheimer's disease symptoms. Resolving respiratory events during sleep often
      has a beneficial impact on these consequences. However, even after adequate and optimized
      treatment with continuous positive airway pressure (CPAP), about 6 to 10% of patients still
      remain sleepy. Given the high prevalence of OSA, this percentage represents a large number of
      under-treated and at-risk individuals. This residual excessive sleepiness (RES) may be
      related to comorbidities and cognitive alterations. Its physiopathology is still unknown. A
      few studies have tested modafinil as an adjunct treatment for RES patients. Since a) CPAP is
      ineffective in patients with RES; b) previous studies suggest some benefit with wake
      promoters; and c) cognitive impairment has also been reported associated with RES; the
      hypothesis of the present study is that donepezil improves alertness and cognition in
      patients with OSA and RES, evidencing the role of the cholinergic system in the
      pathophysiology of RES.

      Objective: To evaluate the effects of donepezil on RES in adult patients treated with CPAP.

      Thirty-six patients diagnosed with OSA and RES are estimated to be included. Participants
      will be treated with CPAP for more than 6 months with a mean use greater than 5 hours per
      day. After blood and cerebrospinal fluid collection, patients will be randomized into 2
      groups of 30 days of treatment with donepezil or placebo. RES will be evaluated by the
      vigilance test and the Epworth Sleepiness Scale.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, parallel groups, 30-day trial
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: donepezil and placebo will be dispensed to volunteers in similar pills and numbered boxes.
measure: objective excessive daytime sleepiness
time frame: 40 days
description: Maintenance Wakefulness Test
measure: subjective excessive daytime sleepiness
time frame: 40 days
description: Epworth Sleepiness Scale
measure: cognitive improvement (executive functions)
time frame: 40 days
description: standard cognitive tests to evaluate executive functions
arm group label: donepezil treatment
arm group type: Active Comparator
description: donepezil with 10 mg will be administered for 30 days.
arm group label: placebo treatment
arm group type: Placebo Comparator
description: placebo with 10 mg placebo will be administered for 30 days.
intervention type: Drug
intervention name: donepezil treatment
description: 30-day donepezil treatment
arm group label: donepezil treatment
arm group label: placebo treatment
criteria: 
gender: All
minimum age: 35 Years
maximum age: 60 Years
healthy volunteers: No
last name: Ksdy Maiara Werli, Psy
phone: +55-11-958491512
email: ksdymaiara@yahoo.com.br
last name: Dalva Poyares, MD
phone: +55-11-985937418
email: poyares@unifesp.br
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Associação Fundo de Incentivo à Pesquisa
investigator full name: Dalva Poyares
investigator title: MD Professor
mesh term: Sleepiness
mesh term: Donepezil
sharing ipd: Undecided