<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/NCT01661712</url>
  </required_header>
  <id_info>
    <org_study_id>SOSATS2012-V1.0-01/08/2012</org_study_id>
    <nct_id>NCT01661712</nct_id>
  </id_info>
  <brief_title>Continuous Transcutaneous Electrical Stimulation in Sleep Apnoea</brief_title>
  <acronym>TESLA</acronym>
  <official_title>Randomised, Double-blinded, Sham-controlled Cross-over Trial of Continuous Transcutaneous Electrical Stimulation of the Pharyngeal Dilator Muscles in Obstructive Sleep Apnoea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Guy's and St Thomas' NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this randomized, double-blinded, sham-controlled cross-over trial is to&#xD;
      demonstrate the effectiveness of continuous transcutaneous electrical stimulation of the&#xD;
      pharyngeal dilator muscles to reduce sleep-disordered breathing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obstructive sleep apnoea is the most common problem of sleep-disordered breathing. It affects&#xD;
      at least four percent of the male and two percent of the female adult population. It is&#xD;
      associated with excessive daytime sleepiness, causing significant disturbance of daytime&#xD;
      routines affecting work, social life and memory; untreated, it also causes a significant&#xD;
      cardiovascular and metabolic risk. The best available treatment for obstructive sleep apnoea&#xD;
      is continuous positive airway pressure (CPAP). However, not everyone eligible tolerates this&#xD;
      treatment because it requires them to sleep with a nasal or full-face mask that is connected&#xD;
      by a tube to a machine. Although CPAP is recommended by the National Institute for Health and&#xD;
      Clinical Excellence (NICE) for moderate-severe sleep apnoea, approximately one third of sleep&#xD;
      apnoea patients who should be on CPAP stop therapy within five years. Mild sleep apnoea is&#xD;
      currently treated with mandibular advancement splints and generic sleep hygiene advice.&#xD;
&#xD;
      Continuous transcutaneous electrical stimulation (CTES) of the submental region activates the&#xD;
      muscles that dilate the upper airway. This is where airway obstruction occurs in sleep&#xD;
      apnoea. It has been shown that CTES at night for short periods (10minutes) effectively&#xD;
      stimulates the genioglossus muscle, the strongest pharyngeal dilator and reduces upper airway&#xD;
      obstruction, work of breathing and neural respiratory drive in patients with sleep apnoea.&#xD;
      The London Respiratory Muscle Groups, based within King's Health Partners and the Royal&#xD;
      Brompton Hospital, has developed a CTES stimulator device. This device senses apnoeas and&#xD;
      snoring and delivers CTES until normal ventilation has been restored.&#xD;
&#xD;
      We propose to undertake a randomized, double-blinded, sham-controlled cross-over trial with&#xD;
      sleep apnoea patients to evaluate the efficacy of this method. Patients will be randomly&#xD;
      assigned to a night of CTES or sham-stimulation. The primary outcome measure is the number of&#xD;
      oxygen desaturations per hour (ODI) caused by apnoeas and the secondary outcome measures are&#xD;
      sleepiness, as measured by the Epworth sleepiness score, the apnoea-hypopnoea-index (AHI) and&#xD;
      comfort, as assessed by a visual analogue score. The sample size Calculation using data from&#xD;
      our own published pilot study revealed that this study would require 44 patients to be&#xD;
      enroled. The mean study duration until all outcomes will be assessed for each patient will be&#xD;
      four weeks. We plan to commence the study in winter 2012/13 for a period of two years,&#xD;
      including analysis and publication, to be concluded in December 2014.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>4% Oxygen Desaturation Index (ODI, 4%)</measure>
    <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
    <description>The primary outcome measure for this trial is the 4% oxygen desaturation index (ODI, 4%) per hour of sleep (h-1). The 4% ODI was chosen as primary outcome parameter over the AHI because an incomplete re-opening of the upper airway during an ongoing apnoeic effort caused by transcutaneous electrical stimulation (CTES) may result in a nominal increase of the AHI. We consider that the 4% ODI would be a more robust marker for the severity of sleep apnoea, low average oxygen levels indicating obesity-hypoventilation syndrome which will be an exclusion criterion.&#xD;
Although a specific cut off is not well defined a 4% ODI ≥5 represent mild OSA whilst a 4% ODI ≥15 represents moderate-severe OSA. Normal range is usually considered 0-5 events/hour.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Apnoea-Hypopnoea Index (AHI)</measure>
    <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
    <description>The 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. An apnea (pause in breathing) is defined by a temporary cessation of breathing that must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A hypopnoea is a reduction of ventilation (shallow breathing) but not a complete cessation of breathing, lasting al least 10 seconds and associated with a decrease in blood oxygenation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nadir Oxygenation</measure>
    <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
    <description>The nadir oxygenation (lowest SpO2, %) during the sleep study is measured while the patients are asleep.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Comfort</measure>
    <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
    <description>Patient comfort during the sleep study, as measured by a visual analogue scale (0-10 points). Higher values in the scale range represent a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Device Acceptance</measure>
    <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
    <description>Device acceptance during sleep study, as measured by a visual analogue scale (0-10points). Higher values in the scale range represent a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleepiness</measure>
    <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
    <description>Daytime sleepiness as an ad-hoc measurement, as measured by the Stanford Sleepiness Scale (0-7 points, x). Higher values in the scale range represent more severe sleepiness.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Obstructive Sleep Apnoea</condition>
  <arm_group>
    <arm_group_label>Transcutaneous electrical stimulation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>One night of transcutaneous electrical stimulation (electrical current titrated according to skin sensation)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>One night of sham stimulation (no electrical current)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcutaneous electrical stimulation</intervention_name>
    <description>Transcutaneous electrical stimulation (one night of electrical current titrated according to skin sensation)</description>
    <arm_group_label>Transcutaneous electrical stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham stimulation</intervention_name>
    <description>Sham stimulation for one night (no electrical stimulation)</description>
    <arm_group_label>Sham stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  males and females, age &gt;18years and &lt;75years, body-mass index (BMI) &gt;18 and &lt;40kg/m2,&#xD;
             non-smokers, sleep apnoea with an ODI ≥15/h or sleep apnoea with an ODI ≥5/h plus an&#xD;
             Epworth sleepiness score &gt;10.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  morbid obesity (BMI&gt;40kg/m2) or cachexia (BMI&lt;18kg/m2), obesity-hypoventilation&#xD;
             syndrome (total sleep time with oxygen saturation (SpO2) less than 90% of more than&#xD;
             10% of the night), active smokers or smoking history of &gt;20pack years, acute or&#xD;
             critical illness, acute psychosis or chronic mental disorder affecting capacity,&#xD;
             previous home-mechanical non-invasive ventilation and metal implants in the upper part&#xD;
             of the body (this excludes dental implants).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joerg Steier, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guy´s &amp; St Thomas´ NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Guy´s &amp; St Thomas´ NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.gstt.nhs.uk</url>
    <description>Guy's &amp; St Thomas' National Health Service (NHS) Foundation Trust homepage</description>
  </link>
  <results_reference>
    <citation>Steier J, Seymour J, Rafferty GF, Jolley CJ, Solomon E, Luo Y, Man WD, Polkey MI, Moxham J. Continuous transcutaneous submental electrical stimulation in obstructive sleep apnea: a feasibility study. Chest. 2011 Oct;140(4):998-1007. doi: 10.1378/chest.10-2614. Epub 2011 Mar 31.</citation>
    <PMID>21454399</PMID>
  </results_reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>August 2, 2012</study_first_submitted>
  <study_first_submitted_qc>August 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <results_first_submitted>August 10, 2016</results_first_submitted>
  <results_first_submitted_qc>February 25, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">November 2, 2018</results_first_posted>
  <last_update_submitted>November 14, 2018</last_update_submitted>
  <last_update_submitted_qc>November 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Guy's and St Thomas' NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Joerg Steier</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>obstructive sleep apnoea,</keyword>
  <keyword>continuous transcutaneous electrical stimulation</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>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This is a randomised, sham-controlled crossover trial using transcutaneous electrical stimulation of the upper airway dilator muscles in patients with confirmed obstructive sleep apnea (OSA).</recruitment_details>
      <pre_assignment_details>A total of 390 patients were assessed, 44 patients were screened. 8 patients were excluded as screening failures. 36 patients were randomised into the sequence 'Sham Stimulation, then True Stimulation' (n=18) or 'True Stimulation, then Sham Stimulation' (n-18). All 36 randomised subjects completed the trial, serving as their own control.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Sham Stimulation, Then True Stimulation</title>
          <description>The patient will 1st undergo a sleep study with Sham stimulation. An identical setup to the intervention will be used with the software indicating stimulation to keep staff blinded to the intervention.&#xD;
Then patients will undergo a washout period (&gt;3nights) and return for a 2nd sleep study on true stimulation to complete the trial.&#xD;
Transcutaneous electrical stimulation (SOSATS device, MORGAN Innovation&amp;Technology Ltd., Petersfield, UK):&#xD;
The SOSATS unit is a first generation sleep apnoea research device which is programmed and controlled by an external personal computer (PC) or laptop via a visual interface. It stimulates the pharyngeal dilator muscles to reduce sleep apnoea.</description>
        </group>
        <group group_id="P2">
          <title>Transcutaneous Electrical Stimulation, Then Sham Stimulation</title>
          <description>The patient will undergo the 1st sleep study with continuous transcutaneous electrical stimulation.&#xD;
Then patients will undergo a washout period (&gt;3nights) and return for a 2nd sleep study on sham stimulation to complete the trial.&#xD;
Transcutaneous electrical stimulation (SOSATS device, MORGAN Innovation&amp;Technology ltd., Petersfield, UK):&#xD;
The SOSATS unit is a first generation sleep apnoea research device which is programmed and controlled by an external PC or laptop via a visual interface. It stimulates the pharyngeal dilator muscles to reduce sleep apnoea.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18">initial sham stimulation night</participants>
                <participants group_id="P2" count="18">initial night on transcutaneous electrical stimulation</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Washout Period</title>
              <participants_list>
                <participants group_id="P1" count="18">&gt;Three nights of no stimulation/sham stimulation</participants>
                <participants group_id="P2" count="18">&gt;Three nights of no stimulation/sham stimulation</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18">night on transcutaneous electrical stimulation</participants>
                <participants group_id="P2" count="18">sham stimulation night</participants>
              </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>Sham Stimulation First, Then Transcutaneous Electrical Stimula</title>
          <description>The patient will undergo a sleep study and continuous transcutaneous electrical stimulation will be administered during the night. After 3 days of wash out the patient will undergo a sleep study with the sham intervention and no continuous transcutaneous electrical stimulation will be administered.&#xD;
An identical setup to the intervention will be used with the software indicating stimulation to keep staff blinded to the intervention.&#xD;
Transcutaneous electrical stimulation (SOSATS device, MORGAN Innovation&amp;Technology ltd., Petersfield, UK): The SOSATS unit is a first generation sleep apnoea research device which is programmed and controlled by an external PC or laptop via a visual interface.&#xD;
It stimulates the pharyngeal dilator muscles in order to reduce sleep apnoea.</description>
        </group>
        <group group_id="B2">
          <title>Transcutaneous Electrical Stimulation First, Then Sham Stimula</title>
          <description>The patient will undergo a sleep study with Sham stimulation. After 3 days of wash out the patient will will undergo a sleep study and continuous transcutaneous electrical stimulation will be administered during the night An identical setup to the intervention will be used with the software indicating stimulation to keep staff blinded to the intervention.&#xD;
Transcutaneous electrical stimulation (SOSATS device, MORGAN Innovation&amp;Technology ltd., Petersfield, UK): The SOSATS unit is a first generation sleep apnoea research device which is programmed and controlled by an external PC or laptop via a visual interface.&#xD;
It stimulates the pharyngeal dilator muscles in order to reduce sleep apnoea.</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="18"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="36"/>
          </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="51.2" spread="11.9"/>
                    <measurement group_id="B2" value="50.6" spread="11"/>
                    <measurement group_id="B3" value="50.8" spread="11.2"/>
                  </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="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>4% Oxygen Desaturation Index (ODI, 4%)</title>
        <description>The primary outcome measure for this trial is the 4% oxygen desaturation index (ODI, 4%) per hour of sleep (h-1). The 4% ODI was chosen as primary outcome parameter over the AHI because an incomplete re-opening of the upper airway during an ongoing apnoeic effort caused by transcutaneous electrical stimulation (CTES) may result in a nominal increase of the AHI. We consider that the 4% ODI would be a more robust marker for the severity of sleep apnoea, low average oxygen levels indicating obesity-hypoventilation syndrome which will be an exclusion criterion.&#xD;
Although a specific cut off is not well defined a 4% ODI ≥5 represent mild OSA whilst a 4% ODI ≥15 represents moderate-severe OSA. Normal range is usually considered 0-5 events/hour.</description>
        <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sham Stimulation</title>
            <description>patients that underwent the Sham stimulation night study</description>
          </group>
          <group group_id="O2">
            <title>Active Treatment</title>
            <description>Patients that underwent the stimulation overnight sleep study</description>
          </group>
        </group_list>
        <measure>
          <title>4% Oxygen Desaturation Index (ODI, 4%)</title>
          <description>The primary outcome measure for this trial is the 4% oxygen desaturation index (ODI, 4%) per hour of sleep (h-1). The 4% ODI was chosen as primary outcome parameter over the AHI because an incomplete re-opening of the upper airway during an ongoing apnoeic effort caused by transcutaneous electrical stimulation (CTES) may result in a nominal increase of the AHI. We consider that the 4% ODI would be a more robust marker for the severity of sleep apnoea, low average oxygen levels indicating obesity-hypoventilation syndrome which will be an exclusion criterion.&#xD;
Although a specific cut off is not well defined a 4% ODI ≥5 represent mild OSA whilst a 4% ODI ≥15 represents moderate-severe OSA. Normal range is usually considered 0-5 events/hour.</description>
          <units>oxygen desaturation 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="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.9" lower_limit="17.5" upper_limit="39.5"/>
                    <measurement group_id="O2" value="19.5" lower_limit="11.6" upper_limit="40.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apnoea-Hypopnoea Index (AHI)</title>
        <description>The 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. An apnea (pause in breathing) is defined by a temporary cessation of breathing that must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A hypopnoea is a reduction of ventilation (shallow breathing) but not a complete cessation of breathing, lasting al least 10 seconds and associated with a decrease in blood oxygenation.</description>
        <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sham Stimulation</title>
            <description>sham stimulation night</description>
          </group>
          <group group_id="O2">
            <title>Transcutaneous Electrical Stimulation</title>
            <description>Transcutaneous electrical stimulation night</description>
          </group>
        </group_list>
        <measure>
          <title>Apnoea-Hypopnoea Index (AHI)</title>
          <description>The 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. An apnea (pause in breathing) is defined by a temporary cessation of breathing that must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A hypopnoea is a reduction of ventilation (shallow breathing) but not a complete cessation of breathing, lasting al least 10 seconds and associated with a decrease in blood oxygenation.</description>
          <units>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="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.8" lower_limit="16.6" upper_limit="46.1"/>
                    <measurement group_id="O2" value="23.7" lower_limit="11.4" upper_limit="47.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Nadir Oxygenation</title>
        <description>The nadir oxygenation (lowest SpO2, %) during the sleep study is measured while the patients are asleep.</description>
        <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Transcutaneous Electrical Stimulation</title>
            <description>Transcutaneous electrical stimulation: the patient will undergo a sleep study and continuous transcutaneous electrical stimulation during the night (&quot;active treatment&quot;).&#xD;
Transcutaneous electrical stimulation (SOSATS device, MORGAN Innovation&amp;Technology ltd., Petersfield, UK): The SOSATS unit is a first generation sleep apnoea research device which is programmed and controlled by an external PC or laptop via a visual interface.&#xD;
It stimulates the pharyngeal dilator muscles in order to reduce sleep apnoea.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Sham stimulation: the patient will undergo a sleep study with Sham stimulation. An identical setup to the intervention will be used with the software indicating stimulation to keep staff blinded to the intervention (Modes are labelled &quot;A&quot; and &quot;B&quot; for real and sham stimulation and observers will not be able to tell the difference on the screen).&#xD;
Sham stimulation (SOSATS device, MORGAN Innovation&amp;Technology ltd., Petersfield, UK): The patient will undergo a sleep study with sham transcutaneous electrical stimulation. The setup will be identical to the intervention, but a blinded mode in the software application will stop triggering electrical current despite indicating on the monitor that stimulation is being applied.</description>
          </group>
        </group_list>
        <measure>
          <title>Nadir Oxygenation</title>
          <description>The nadir oxygenation (lowest SpO2, %) during the sleep study is measured while the patients are asleep.</description>
          <units>% of haemoglobin that is oxygenated</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="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.0" lower_limit="74.0" upper_limit="84.0"/>
                    <measurement group_id="O2" value="80.5" lower_limit="74.5" upper_limit="86.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Comfort</title>
        <description>Patient comfort during the sleep study, as measured by a visual analogue scale (0-10 points). Higher values in the scale range represent a better outcome.</description>
        <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Transcutaneous Electrical Stimulation</title>
            <description>Transcutaneous electrical stimulation night</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Sham stimulation night</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Comfort</title>
          <description>Patient comfort during the sleep study, as measured by a visual analogue scale (0-10 points). Higher values in the scale range represent a better outcome.</description>
          <units>units on a scale</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="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" lower_limit="2.4" upper_limit="8.0"/>
                    <measurement group_id="O2" value="5.6" lower_limit="2.9" upper_limit="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Device Acceptance</title>
        <description>Device acceptance during sleep study, as measured by a visual analogue scale (0-10points). Higher values in the scale range represent a better outcome.</description>
        <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sham Stimulation</title>
            <description>patients that underwent the Sham stimulation night study</description>
          </group>
          <group group_id="O2">
            <title>Active Treatment</title>
            <description>Patients that underwent the stimulation overnight sleep study</description>
          </group>
        </group_list>
        <measure>
          <title>Device Acceptance</title>
          <description>Device acceptance during sleep study, as measured by a visual analogue scale (0-10points). Higher values in the scale range represent a better outcome.</description>
          <units>units on a scale</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="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.9" lower_limit="9.5" upper_limit="10.0"/>
                    <measurement group_id="O2" value="9.9" lower_limit="9.7" upper_limit="10.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sleepiness</title>
        <description>Daytime sleepiness as an ad-hoc measurement, as measured by the Stanford Sleepiness Scale (0-7 points, x). Higher values in the scale range represent more severe sleepiness.</description>
        <time_frame>1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Transcutaneous Electrical Stimulation</title>
            <description>Transcutaneous electrical stimulation: the patient will undergo a sleep study and continuous transcutaneous electrical stimulation during the night (&quot;active treatment&quot;).&#xD;
Transcutaneous electrical stimulation (SOSATS device, MORGAN Innovation&amp;Technology ltd., Petersfield, UK): The SOSATS unit is a first generation sleep apnoea research device which is programmed and controlled by an external PC or laptop via a visual interface.&#xD;
It stimulates the pharyngeal dilator muscles in order to reduce sleep apnoea.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Sham stimulation: the patient will undergo a sleep study with Sham stimulation. An identical setup to the intervention will be used with the software indicating stimulation to keep staff blinded to the intervention (Modes are labelled &quot;A&quot; and &quot;B&quot; for real and sham stimulation and observers will not be able to tell the difference on the screen).&#xD;
Sham stimulation (SOSATS device, MORGAN Innovation&amp;Technology ltd., Petersfield, UK): The patient will undergo a sleep study with sham transcutaneous electrical stimulation. The setup will be identical to the intervention, but a blinded mode in the software application will stop triggering electrical current despite indicating on the monitor that stimulation is being applied.</description>
          </group>
        </group_list>
        <measure>
          <title>Sleepiness</title>
          <description>Daytime sleepiness as an ad-hoc measurement, as measured by the Stanford Sleepiness Scale (0-7 points, x). Higher values in the scale range represent more severe sleepiness.</description>
          <units>units on a scale</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="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" lower_limit="2.0" upper_limit="3.0"/>
                    <measurement group_id="O2" value="3.0" lower_limit="2.0" upper_limit="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Sham Stimulation</title>
          <description>patients that underwent the Sham stimulation night study</description>
        </group>
        <group group_id="E2">
          <title>Active Treatment</title>
          <description>Patients that underwent the stimulation overnight sleep study</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="36"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>claustrophobia</sub_title>
                <description>The only significant side effect observed was one patient who complained about claustrophobia at night; this was during both treatment nights</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="36"/>
              </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>
    <point_of_contact>
      <name_or_title>Dr Joerg Steier</name_or_title>
      <organization>2Guy's and St Thomas' NHS Foundation Trust, Lane Fox Respiratory Unit/Sleep Disorders Centre, London, UK</organization>
      <phone>020 7188 3430</phone>
      <email>joerg.steier@gstt.nhs.uk</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/NCT01661712
org study id: SOSATS2012-V1.0-01/08/2012
nct id: NCT01661712
lead sponsor: 
has dmc: Yes
The aim of this randomized, double-blinded, sham-controlled cross-over trial is to
      demonstrate the effectiveness of continuous transcutaneous electrical stimulation of the
      pharyngeal dilator muscles to reduce sleep-disordered breathing.
Obstructive sleep apnoea is the most common problem of sleep-disordered breathing. It affects
      at least four percent of the male and two percent of the female adult population. It is
      associated with excessive daytime sleepiness, causing significant disturbance of daytime
      routines affecting work, social life and memory; untreated, it also causes a significant
      cardiovascular and metabolic risk. The best available treatment for obstructive sleep apnoea
      is continuous positive airway pressure (CPAP). However, not everyone eligible tolerates this
      treatment because it requires them to sleep with a nasal or full-face mask that is connected
      by a tube to a machine. Although CPAP is recommended by the National Institute for Health and
      Clinical Excellence (NICE) for moderate-severe sleep apnoea, approximately one third of sleep
      apnoea patients who should be on CPAP stop therapy within five years. Mild sleep apnoea is
      currently treated with mandibular advancement splints and generic sleep hygiene advice.

      Continuous transcutaneous electrical stimulation (CTES) of the submental region activates the
      muscles that dilate the upper airway. This is where airway obstruction occurs in sleep
      apnoea. It has been shown that CTES at night for short periods (10minutes) effectively
      stimulates the genioglossus muscle, the strongest pharyngeal dilator and reduces upper airway
      obstruction, work of breathing and neural respiratory drive in patients with sleep apnoea.
      The London Respiratory Muscle Groups, based within King's Health Partners and the Royal
      Brompton Hospital, has developed a CTES stimulator device. This device senses apnoeas and
      snoring and delivers CTES until normal ventilation has been restored.

      We propose to undertake a randomized, double-blinded, sham-controlled cross-over trial with
      sleep apnoea patients to evaluate the efficacy of this method. Patients will be randomly
      assigned to a night of CTES or sham-stimulation. The primary outcome measure is the number of
      oxygen desaturations per hour (ODI) caused by apnoeas and the secondary outcome measures are
      sleepiness, as measured by the Epworth sleepiness score, the apnoea-hypopnoea-index (AHI) and
      comfort, as assessed by a visual analogue score. The sample size Calculation using data from
      our own published pilot study revealed that this study would require 44 patients to be
      enroled. The mean study duration until all outcomes will be assessed for each patient will be
      four weeks. We plan to commence the study in winter 2012/13 for a period of two years,
      including analysis and publication, to be concluded in December 2014.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: 4% Oxygen Desaturation Index (ODI, 4%)
time frame: 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)
description: The primary outcome measure for this trial is the 4% oxygen desaturation index (ODI, 4%) per hour of sleep (h-1). The 4% ODI was chosen as primary outcome parameter over the AHI because an incomplete re-opening of the upper airway during an ongoing apnoeic effort caused by transcutaneous electrical stimulation (CTES) may result in a nominal increase of the AHI. We consider that the 4% ODI would be a more robust marker for the severity of sleep apnoea, low average oxygen levels indicating obesity-hypoventilation syndrome which will be an exclusion criterion.
Although a specific cut off is not well defined a 4% ODI ≥5 represent mild OSA whilst a 4% ODI ≥15 represents moderate-severe OSA. Normal range is usually considered 0-5 events/hour.
measure: Apnoea-Hypopnoea Index (AHI)
time frame: 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)
description: The 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. An apnea (pause in breathing) is defined by a temporary cessation of breathing that must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A hypopnoea is a reduction of ventilation (shallow breathing) but not a complete cessation of breathing, lasting al least 10 seconds and associated with a decrease in blood oxygenation.
measure: Nadir Oxygenation
time frame: 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)
description: The nadir oxygenation (lowest SpO2, %) during the sleep study is measured while the patients are asleep.
measure: Patient Comfort
time frame: 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)
description: Patient comfort during the sleep study, as measured by a visual analogue scale (0-10 points). Higher values in the scale range represent a better outcome.
measure: Device Acceptance
time frame: 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)
description: Device acceptance during sleep study, as measured by a visual analogue scale (0-10points). Higher values in the scale range represent a better outcome.
measure: Sleepiness
time frame: 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)
description: Daytime sleepiness as an ad-hoc measurement, as measured by the Stanford Sleepiness Scale (0-7 points, x). Higher values in the scale range represent more severe sleepiness.
arm group label: Transcutaneous electrical stimulation
arm group type: Active Comparator
description: One night of transcutaneous electrical stimulation (electrical current titrated according to skin sensation)
arm group label: Sham stimulation
arm group type: Sham Comparator
description: One night of sham stimulation (no electrical current)
intervention type: Device
intervention name: Transcutaneous electrical stimulation
description: Transcutaneous electrical stimulation (one night of electrical current titrated according to skin sensation)
arm group label: Transcutaneous electrical stimulation
intervention type: Device
intervention name: Sham stimulation
description: Sham stimulation for one night (no electrical stimulation)
arm group label: Sham stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Joerg Steier, MD, PhD
role: Principal Investigator
affiliation: Guy´s & St Thomas´ NHS Foundation Trust
facility: 
country: United Kingdom
url: http://www.gstt.nhs.uk
description: Guy's & St Thomas' National Health Service (NHS) Foundation Trust homepage
citation: Steier J, Seymour J, Rafferty GF, Jolley CJ, Solomon E, Luo Y, Man WD, Polkey MI, Moxham J. Continuous transcutaneous submental electrical stimulation in obstructive sleep apnea: a feasibility study. Chest. 2011 Oct;140(4):998-1007. doi: 10.1378/chest.10-2614. Epub 2011 Mar 31.
PMID: 21454399
responsible party type: Principal Investigator
investigator affiliation: Guy's and St Thomas' NHS Foundation Trust
investigator full name: Joerg Steier
investigator title: MD, PhD
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 