<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/NCT03760328</url>
  </required_header>
  <id_info>
    <org_study_id>EFFECT</org_study_id>
    <nct_id>NCT03760328</nct_id>
  </id_info>
  <brief_title>Effect of Upper Airway Stimulation in Patients With Obstructive Sleep Apnea</brief_title>
  <acronym>EFFECT</acronym>
  <official_title>Effect of Upper Airway Stimulation: A Randomized Controlled Crossover Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Technical University of Munich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universitätsmedizin Mannheim</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Luebeck</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Technical University of Munich</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>
      Upper Airway Stimulation is a new therapy, which is available for patients with obstructive&#xD;
      sleep apnea, who are non-compliant to the standard treatment continuous positive airway&#xD;
      pressure (CPAP) therapy. This study is a prospective, multi-center, double-blinded,&#xD;
      randomized crossover study conducted under a common protocol. The study visits include&#xD;
      baseline with an in-laboratory polysomnography (PSG) after six months of therapy usage,&#xD;
      followed by visits and in-lab PSGs at 1 and 2-weeks where the Therapy stimulation will be&#xD;
      changed at each, according to randomization. The objective of this randomized controlled&#xD;
      crossover study is to assess treatment effect of Inspire UAS in patients at different time&#xD;
      points with two different therapy settings. This study will provide additional clinical&#xD;
      evidence of Inspire UAS for treatment of moderate to severe OSA using a randomized controlled&#xD;
      crossover trial design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obstructive Sleep Apnea (OSA) is characterized by recurrent episodes of airflow obstruction&#xD;
      in the upper airway that results in oxygen desaturations and arousal from sleep. The most&#xD;
      common symptom of OSA is excessive daytime sleepiness. Recent studies have also shown clear&#xD;
      association of OSA with the development of obesity, hypertension diabetes mellitus, and&#xD;
      congestive heart failure. Approximately 13% men and 6% women have moderate to severe OSA&#xD;
      (apnea hypopnea index, AHI ≥ 15) in the US.&#xD;
&#xD;
      The efficacy of therapies for OSA, and in particular, continuous positive airway pressure&#xD;
      (CPAP) has been limited due to patient intolerance, poor patient selection, or limited&#xD;
      response to the therapy.&#xD;
&#xD;
      The Inspire Upper Airway Stimulation (UAS) system is intended to prevent upper airway&#xD;
      obstruction by stimulating the hypoglossal nerve synchronous with respiration [7].&#xD;
&#xD;
      The Inspire system is comprised of the following components:&#xD;
&#xD;
        -  Inspire Upper Airway Stimulator (Implantable Pulse Generator (IPG))&#xD;
&#xD;
        -  Inspire Stimulation Lead&#xD;
&#xD;
        -  Inspire Sensing Lead&#xD;
&#xD;
        -  External programmers used with the system are:&#xD;
&#xD;
             -  Inspire Programmer (physician programmer)&#xD;
&#xD;
             -  Inspire Patient Programmer (patient remote)&#xD;
&#xD;
      The Inspire system received CE Mark in 2010 (CE Certificate No. 562872) providing the&#xD;
      regulatory authority to provide the device in a commercial setting. Furthermore, this study&#xD;
      will be conducted within the CE marked intended use of the Inspire system and will not&#xD;
      involve any additional stressful or invasive tests.&#xD;
&#xD;
      The objective of this randomized controlled crossover study is to assess treatment effect of&#xD;
      Inspire UAS in patients at different time points with two different therapy settings. This&#xD;
      study will provide additional clinical evidence of Inspire UAS for treatment of moderate to&#xD;
      severe OSA using a randomized controlled crossover trial design.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 16, 2019</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">May 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>Crossover Assignment</intervention_model>
    <intervention_model_description>This study is a prospective, multi-center, randomized, crossover study, conducted under a common protocol. Subjects will be enrolled after they have been implanted and using the Inspire therapy (Inspire II/IV, Inspire Medical Systems, Maple Grove, USA) for at least six months. Participants will be randomized to one of two groups: therapeutic stimulation or sham stimulation. During the second phase of the study therapy settings of the stimulation system will be adjusted to crossover.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Neither the subject nor the investigator or Outcomes Assessor (double-blinded) will know the outcome of the randomization until after the subject has fulfilled and completed all study requirements at the end of the visit 3.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in AHI from Baseline to Visit 1 and Visit 2</measure>
    <time_frame>Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)</time_frame>
    <description>Apnea Hypopnea Index (AHI) is a measure of OSA severity. The AHI in this study will be determined by the AHI score at Visit 1 and Visit 2 compared with the baseline score.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in ESS from Baseline to Visit 1 and Visit 2</measure>
    <time_frame>Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)</time_frame>
    <description>The Epworth Sleepiness Scale (ESS) is a validated instruction that rates a subject's daytime sleepiness. The ESS efficacy endpoint will be determined by the ESS score at Visit 1 and Visit 2 as compared to baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in FOSQ from Baseline to Visit 1 and Visit 2</measure>
    <time_frame>Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)</time_frame>
    <description>The Functional Outcomes of Sleep Questionnaire (FOSQ) is a validated instrument to assess the effect of a subject's daytime sleepiness on activities of ordinary living. The FOSQ endpoint will be determined by the FOSQ score at Visit 1 and Visit 2 as compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Snoring Intensity from Baseline to Visit 1 and Visit 2</measure>
    <time_frame>Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)</time_frame>
    <description>Snoring Intensity will be measured by using a visual analoge scale from 0 (no snoring) to 10 (heavy snoring). The snoring intensity endpoint will be determined by the visual analogue scale at Visit 1 and Visit 2 as compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Therapy Adherence</measure>
    <time_frame>Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)</time_frame>
    <description>Therapy use, reported as hours of use per week, is record by Inspire device and can be collected upon interrogation of the device in the clinic. This value can be used to quantify device use and adherence over the investigated time period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ODI from Baseline to Visit 1 and Visit 2</measure>
    <time_frame>Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)</time_frame>
    <description>Oxygen Desaturation Index (ODI) is a measure of OSA severity. The ODI will be determined by the ODI score at Visit 1 and Visit 2 as compared with to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Global Impression (CGI-I) from Baseline to Visit 1 and Visit 2</measure>
    <time_frame>Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)</time_frame>
    <description>The CGI-I is a seven point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Obstructive Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>therapeutic stimulation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Therapeutic Stimulation: optimal therapy setting for home use</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sham stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham Stimulation (Control Group): stimulation voltage programmed at 0.1 volts</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Upper Airway Stimulation</intervention_name>
    <description>hypoglossal nerve stimulation by using a breathing cycle depended stimulation system of the upper airway</description>
    <arm_group_label>sham stimulation</arm_group_label>
    <arm_group_label>therapeutic stimulation</arm_group_label>
    <other_name>Inspire</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Otherwise healthy subjects that are at least 18 years old and:&#xD;
&#xD;
               1. Have been implanted and using the Inspire Therapy for at least six months&#xD;
&#xD;
               2. Willing and capable to undergo three in-lab PSGs in a one-month timeframe&#xD;
&#xD;
               3. Willing and capable of having reduced Inspire stimulation for one week&#xD;
&#xD;
               4. Willing and capable of providing informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who meet any of the following criteria will be excluded from this clinical&#xD;
             investigation:&#xD;
&#xD;
               1. Unwilling to complete three in-lab PSGs within a 1-month timeframe&#xD;
&#xD;
               2. Any other reason the investigator deems subject is unfit for participation in the&#xD;
                  study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clemens Heiser, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Klinikum rechts der Isar, Technical University of Munich</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Ear Nose Throat</name>
      <address>
        <city>Munich</city>
        <state>Bayern</state>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>October 19, 2020</last_update_submitted>
  <last_update_submitted_qc>October 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
  </condition_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/NCT03760328
org study id: EFFECT
nct id: NCT03760328
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Upper Airway Stimulation is a new therapy, which is available for patients with obstructive
      sleep apnea, who are non-compliant to the standard treatment continuous positive airway
      pressure (CPAP) therapy. This study is a prospective, multi-center, double-blinded,
      randomized crossover study conducted under a common protocol. The study visits include
      baseline with an in-laboratory polysomnography (PSG) after six months of therapy usage,
      followed by visits and in-lab PSGs at 1 and 2-weeks where the Therapy stimulation will be
      changed at each, according to randomization. The objective of this randomized controlled
      crossover study is to assess treatment effect of Inspire UAS in patients at different time
      points with two different therapy settings. This study will provide additional clinical
      evidence of Inspire UAS for treatment of moderate to severe OSA using a randomized controlled
      crossover trial design.
Obstructive Sleep Apnea (OSA) is characterized by recurrent episodes of airflow obstruction
      in the upper airway that results in oxygen desaturations and arousal from sleep. The most
      common symptom of OSA is excessive daytime sleepiness. Recent studies have also shown clear
      association of OSA with the development of obesity, hypertension diabetes mellitus, and
      congestive heart failure. Approximately 13% men and 6% women have moderate to severe OSA
      (apnea hypopnea index, AHI ≥ 15) in the US.

      The efficacy of therapies for OSA, and in particular, continuous positive airway pressure
      (CPAP) has been limited due to patient intolerance, poor patient selection, or limited
      response to the therapy.

      The Inspire Upper Airway Stimulation (UAS) system is intended to prevent upper airway
      obstruction by stimulating the hypoglossal nerve synchronous with respiration [7].

      The Inspire system is comprised of the following components:

        -  Inspire Upper Airway Stimulator (Implantable Pulse Generator (IPG))

        -  Inspire Stimulation Lead

        -  Inspire Sensing Lead

        -  External programmers used with the system are:

             -  Inspire Programmer (physician programmer)

             -  Inspire Patient Programmer (patient remote)

      The Inspire system received CE Mark in 2010 (CE Certificate No. 562872) providing the
      regulatory authority to provide the device in a commercial setting. Furthermore, this study
      will be conducted within the CE marked intended use of the Inspire system and will not
      involve any additional stressful or invasive tests.

      The objective of this randomized controlled crossover study is to assess treatment effect of
      Inspire UAS in patients at different time points with two different therapy settings. This
      study will provide additional clinical evidence of Inspire UAS for treatment of moderate to
      severe OSA using a randomized controlled crossover trial design.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This study is a prospective, multi-center, randomized, crossover study, conducted under a common protocol. Subjects will be enrolled after they have been implanted and using the Inspire therapy (Inspire II/IV, Inspire Medical Systems, Maple Grove, USA) for at least six months. Participants will be randomized to one of two groups: therapeutic stimulation or sham stimulation. During the second phase of the study therapy settings of the stimulation system will be adjusted to crossover.
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Neither the subject nor the investigator or Outcomes Assessor (double-blinded) will know the outcome of the randomization until after the subject has fulfilled and completed all study requirements at the end of the visit 3.
measure: Change in AHI from Baseline to Visit 1 and Visit 2
time frame: Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)
description: Apnea Hypopnea Index (AHI) is a measure of OSA severity. The AHI in this study will be determined by the AHI score at Visit 1 and Visit 2 compared with the baseline score.
measure: Change in ESS from Baseline to Visit 1 and Visit 2
time frame: Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)
description: The Epworth Sleepiness Scale (ESS) is a validated instruction that rates a subject's daytime sleepiness. The ESS efficacy endpoint will be determined by the ESS score at Visit 1 and Visit 2 as compared to baseline.
measure: Change in FOSQ from Baseline to Visit 1 and Visit 2
time frame: Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)
description: The Functional Outcomes of Sleep Questionnaire (FOSQ) is a validated instrument to assess the effect of a subject's daytime sleepiness on activities of ordinary living. The FOSQ endpoint will be determined by the FOSQ score at Visit 1 and Visit 2 as compared to baseline.
measure: Change in Snoring Intensity from Baseline to Visit 1 and Visit 2
time frame: Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)
description: Snoring Intensity will be measured by using a visual analoge scale from 0 (no snoring) to 10 (heavy snoring). The snoring intensity endpoint will be determined by the visual analogue scale at Visit 1 and Visit 2 as compared to baseline.
measure: Therapy Adherence
time frame: Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)
description: Therapy use, reported as hours of use per week, is record by Inspire device and can be collected upon interrogation of the device in the clinic. This value can be used to quantify device use and adherence over the investigated time period.
measure: Change in ODI from Baseline to Visit 1 and Visit 2
time frame: Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)
description: Oxygen Desaturation Index (ODI) is a measure of OSA severity. The ODI will be determined by the ODI score at Visit 1 and Visit 2 as compared with to baseline
measure: Change in Clinical Global Impression (CGI-I) from Baseline to Visit 1 and Visit 2
time frame: Baseline through Visit 1 (1 week) and Visit 2 (2 weeks)
description: The CGI-I is a seven point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.
arm group label: therapeutic stimulation
arm group type: Active Comparator
description: Therapeutic Stimulation: optimal therapy setting for home use
arm group label: sham stimulation
arm group type: Sham Comparator
description: Sham Stimulation (Control Group): stimulation voltage programmed at 0.1 volts
intervention type: Device
intervention name: Upper Airway Stimulation
description: hypoglossal nerve stimulation by using a breathing cycle depended stimulation system of the upper airway
arm group label: sham stimulation
arm group label: therapeutic stimulation
other name: Inspire
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clemens Heiser, M.D.
role: Principal Investigator
affiliation: Klinikum rechts der Isar, Technical University of Munich
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
sharing ipd: Undecided