<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/NCT02259660</url>
  </required_header>
  <id_info>
    <org_study_id>IRB201400642</org_study_id>
    <nct_id>NCT02259660</nct_id>
  </id_info>
  <brief_title>Airway Muscle Training for Obstructive Sleep Apnea</brief_title>
  <acronym>OSA</acronym>
  <official_title>Upper Airway Muscle Training for Obstructive Sleep Apnea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>No</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>
      The purpose of this research study is to determine if muscle training will improve snoring&#xD;
      and obstructive sleep apnea. Subjects will receive a sleep study to determine the severity of&#xD;
      their apnea. After this study, subjects will be randomly assigned to one of two groups. The&#xD;
      first group will receiving a breathing trainer that may strengthen the muscles used to breath&#xD;
      in and out. The second group will be receive a sham trainer which looks like the &quot;real&quot;&#xD;
      trainer but is not able to produce a strengthening effect. Both groups will complete eight&#xD;
      weeks of home based (real or sham) training. The sleep study will be repeated and we well&#xD;
      measure any changes in measures of severity for obstructive sleep apnea.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obstructive sleep apnea (OSA) is a common disorder characterized by intermittent narrowing or&#xD;
      closure of the upper airway during sleep. Loss of muscle tone with sleep onset and decreases&#xD;
      in ventilatory drive following the loss of the wakefulness stimuli to breathe combine to&#xD;
      result in upper airway closure in patients with structurally susceptible upper airways. We&#xD;
      hypothesize that training of upper airway muscles will improve sleep apnea by augmenting the&#xD;
      resting upper airway muscle tone and ability of the muscles to respond to negative&#xD;
      intraluminal pressure. Training with a primitive wind instrument (such as a Digeridoo) and&#xD;
      oral pharyngeal exercises (OPE) used in speech therapy have been shown to improve sleep&#xD;
      apnea. Individuals who play certain types of wind instruments appear to have a lower risk of&#xD;
      sleep apnea. However, to date the mechanism of improvement and the optimal method of upper&#xD;
      airway training have not been well defined. We recently completed a study with a facial&#xD;
      exerciser (Facial Flex) designed to improve facial muscle tone and found a decrease in&#xD;
      snoring in a group with loud snoring but minimal sleep apnea. A group of UF physiologists&#xD;
      (including co investigators Drs. Davenport and Silverman) have also demonstrated that brief&#xD;
      periods of training with high inspiratory and/or expiratory threshold loads improved cough&#xD;
      and swallowing in patients with impairment in upper airway function. Although respiratory&#xD;
      pump muscles provide the driving force for pressure generation during training with pressure&#xD;
      threshold loads, the upper airway muscle must maintain a patent upper airway resisting high&#xD;
      negative or positive intraluminal pressures. For example, the palate must maintain a seal&#xD;
      preventing air escape through the nose when high positive pressure is generated through a&#xD;
      mouthpiece. Of interest a limited number of very high intensity efforts appears to be the&#xD;
      optimal way to train muscles.&#xD;
&#xD;
      We propose targeting a group of mild to moderate OSA patients (apnea-hypopnea index &lt;&#xD;
      30/hour) who are not severely obese (BMI &lt; 35 Kg/M2) and do not have significant structural&#xD;
      abnormalities of the upper airway or muscle dysfunction. We will perform a randomized&#xD;
      controlled trial (training versus sham training) with 25 subjects in each treatment arm using&#xD;
      two months of daily training (5 out of 7 days each week). A home sleep study (including EEG)&#xD;
      will be performed before and following the training. The change in the apnea-hypopnea index&#xD;
      adjusted for sleep stage and body position will be compared. Use of home sleep studies will&#xD;
      dramatically reduce the cost of the study. A sleep technologist will educate subjects on&#xD;
      performance of maneuvers and meet with them weekly to observe the subject's technique. A&#xD;
      training log will be kept by the subjects using training schedule sheets and daily training&#xD;
      will be monitored through weekly web-based communication with a study clinician.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2015</start_date>
  <completion_date type="Actual">September 28, 2017</completion_date>
  <primary_completion_date type="Actual">September 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Apnea Hypopnea Index (AHI)</measure>
    <time_frame>Baseline and 10 weeks</time_frame>
    <description>The AHI is a measure of symptom severity for obstructive sleep apnea. Physiological data obtained during a sleep study is used to complete this measure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum inspiratory pressure (MIP)</measure>
    <time_frame>Baseline and 10 weeks</time_frame>
    <description>MIP is an estimate of the strength of respiratory muscles that are used to inhale. Specifically, the diaphragm and external intercostals. This measure is obtained by having the subject inhale forcibly through a mouthpiece connected to a pressure manometer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum expiratory pressure (MEP)</measure>
    <time_frame>Baseline and 10 weeks</time_frame>
    <description>MEP is an estimate of the strength of breathing muscles used for exhalation. Specifically, the abdominals and internal intercostals. MEP is obtained by having the subject exhale forcibly through a mouthpiece that is connected to a pressure manometer.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Obstructive Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>Active Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects in this arm will train their respiratory muscles at home. The training protocol will use progressively higher pressure threshold training valves to provide respiratory muscle strength training at a pressure threshold greater than 70% maximum inspiratory (MIP) and expiratory (MEP) pressures. The total daily training time should be 20 to 30 minutes in duration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Training</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The intervention in the sham training arm will be identical in every way to that of the active arm with the exception of the trainer that is provided. Subjects in the sham training arm will have inspiratory and expiratory muscle strength trainers which have had the pressure threshold spring removed and are therefore unable to provide a load to the muscles being trained.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Respiratory muscle strength training</intervention_name>
    <description>Inspiratory and expiratory muscle strength training occur when subjects are required to breath in (as with inspiratory training) or out (as with expiratory training) through a pressure threshold device. This device features a spring-loaded one way valve which will only open if the subject is able to generate sufficient air pressure to overcome a predetermined pressure threshold. This threshold is typically set at 75% of the subject's maximum capacity. Repeatedly overcoming this threshold during training produces a strengthening effect in most people.</description>
    <arm_group_label>Active Group</arm_group_label>
    <other_name>Inspiratory muscle strength training</other_name>
    <other_name>Expiratory muscle strength training</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham respiratory muscle strength training</intervention_name>
    <description>The placebo / sham intervention will mimic the active intervention(s) in every respect except the devices used will be rendered neutral via removal of the pressure threshold spring inside the devices.</description>
    <arm_group_label>Sham Training</arm_group_label>
    <other_name>Sham inspiratory muscle strength training</other_name>
    <other_name>Sham expiratory muscle strength training</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years,&#xD;
&#xD;
          -  AHI ≥ 5/hour and less than 30/hour&#xD;
&#xD;
          -  Ability to understand and perform training.&#xD;
&#xD;
          -  Ability to return to the UFHealth Sleep Center 1X per week for the (8 week) duration&#xD;
             of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Prior Upper airway surgery (nasal surgery is allowed)&#xD;
&#xD;
          -  Severe nasal obstruction&#xD;
&#xD;
          -  BMI &gt; 35 kg/M2&#xD;
&#xD;
          -  Use of potent narcotics&#xD;
&#xD;
          -  History of arrhythmia (other than PACs and PVCs)&#xD;
&#xD;
          -  Coronary artery disease or congestive heart failure (patients with controlled&#xD;
             hypertension will be included),&#xD;
&#xD;
          -  Moderate to severe lung disease&#xD;
&#xD;
          -  History of pneumothorax.10. severe daytime sleepiness (falling asleep while driving or&#xD;
&#xD;
          -  Epworth Sleepiness Scale [Appendix 1] &gt; 14),&#xD;
&#xD;
          -  History of chronic short sleep duration (&lt; 5 hours).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Berry, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UFHealth Sleep Center</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <last_update_submitted>April 10, 2018</last_update_submitted>
  <last_update_submitted_qc>April 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 11, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>obstructive sleep apnea</keyword>
  <keyword>osa</keyword>
  <keyword>breathing</keyword>
  <keyword>snoring</keyword>
  <keyword>respiratory</keyword>
  <keyword>exercise</keyword>
  <keyword>inspiratory muscle strength training</keyword>
  <keyword>expiratory muscle strength training</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>
  <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/NCT02259660
org study id: IRB201400642
nct id: NCT02259660
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this research study is to determine if muscle training will improve snoring
      and obstructive sleep apnea. Subjects will receive a sleep study to determine the severity of
      their apnea. After this study, subjects will be randomly assigned to one of two groups. The
      first group will receiving a breathing trainer that may strengthen the muscles used to breath
      in and out. The second group will be receive a sham trainer which looks like the "real"
      trainer but is not able to produce a strengthening effect. Both groups will complete eight
      weeks of home based (real or sham) training. The sleep study will be repeated and we well
      measure any changes in measures of severity for obstructive sleep apnea.
Obstructive sleep apnea (OSA) is a common disorder characterized by intermittent narrowing or
      closure of the upper airway during sleep. Loss of muscle tone with sleep onset and decreases
      in ventilatory drive following the loss of the wakefulness stimuli to breathe combine to
      result in upper airway closure in patients with structurally susceptible upper airways. We
      hypothesize that training of upper airway muscles will improve sleep apnea by augmenting the
      resting upper airway muscle tone and ability of the muscles to respond to negative
      intraluminal pressure. Training with a primitive wind instrument (such as a Digeridoo) and
      oral pharyngeal exercises (OPE) used in speech therapy have been shown to improve sleep
      apnea. Individuals who play certain types of wind instruments appear to have a lower risk of
      sleep apnea. However, to date the mechanism of improvement and the optimal method of upper
      airway training have not been well defined. We recently completed a study with a facial
      exerciser (Facial Flex) designed to improve facial muscle tone and found a decrease in
      snoring in a group with loud snoring but minimal sleep apnea. A group of UF physiologists
      (including co investigators Drs. Davenport and Silverman) have also demonstrated that brief
      periods of training with high inspiratory and/or expiratory threshold loads improved cough
      and swallowing in patients with impairment in upper airway function. Although respiratory
      pump muscles provide the driving force for pressure generation during training with pressure
      threshold loads, the upper airway muscle must maintain a patent upper airway resisting high
      negative or positive intraluminal pressures. For example, the palate must maintain a seal
      preventing air escape through the nose when high positive pressure is generated through a
      mouthpiece. Of interest a limited number of very high intensity efforts appears to be the
      optimal way to train muscles.

      We propose targeting a group of mild to moderate OSA patients (apnea-hypopnea index <
      30/hour) who are not severely obese (BMI < 35 Kg/M2) and do not have significant structural
      abnormalities of the upper airway or muscle dysfunction. We will perform a randomized
      controlled trial (training versus sham training) with 25 subjects in each treatment arm using
      two months of daily training (5 out of 7 days each week). A home sleep study (including EEG)
      will be performed before and following the training. The change in the apnea-hypopnea index
      adjusted for sleep stage and body position will be compared. Use of home sleep studies will
      dramatically reduce the cost of the study. A sleep technologist will educate subjects on
      performance of maneuvers and meet with them weekly to observe the subject's technique. A
      training log will be kept by the subjects using training schedule sheets and daily training
      will be monitored through weekly web-based communication with a study clinician.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Apnea Hypopnea Index (AHI)
time frame: Baseline and 10 weeks
description: The AHI is a measure of symptom severity for obstructive sleep apnea. Physiological data obtained during a sleep study is used to complete this measure.
measure: Maximum inspiratory pressure (MIP)
time frame: Baseline and 10 weeks
description: MIP is an estimate of the strength of respiratory muscles that are used to inhale. Specifically, the diaphragm and external intercostals. This measure is obtained by having the subject inhale forcibly through a mouthpiece connected to a pressure manometer.
measure: Maximum expiratory pressure (MEP)
time frame: Baseline and 10 weeks
description: MEP is an estimate of the strength of breathing muscles used for exhalation. Specifically, the abdominals and internal intercostals. MEP is obtained by having the subject exhale forcibly through a mouthpiece that is connected to a pressure manometer.
arm group label: Active Group
arm group type: Active Comparator
description: Subjects in this arm will train their respiratory muscles at home. The training protocol will use progressively higher pressure threshold training valves to provide respiratory muscle strength training at a pressure threshold greater than 70% maximum inspiratory (MIP) and expiratory (MEP) pressures. The total daily training time should be 20 to 30 minutes in duration.
arm group label: Sham Training
arm group type: Placebo Comparator
description: The intervention in the sham training arm will be identical in every way to that of the active arm with the exception of the trainer that is provided. Subjects in the sham training arm will have inspiratory and expiratory muscle strength trainers which have had the pressure threshold spring removed and are therefore unable to provide a load to the muscles being trained.
intervention type: Device
intervention name: Respiratory muscle strength training
description: Inspiratory and expiratory muscle strength training occur when subjects are required to breath in (as with inspiratory training) or out (as with expiratory training) through a pressure threshold device. This device features a spring-loaded one way valve which will only open if the subject is able to generate sufficient air pressure to overcome a predetermined pressure threshold. This threshold is typically set at 75% of the subject's maximum capacity. Repeatedly overcoming this threshold during training produces a strengthening effect in most people.
arm group label: Active Group
other name: Inspiratory muscle strength training
other name: Expiratory muscle strength training
intervention type: Device
intervention name: Sham respiratory muscle strength training
description: The placebo / sham intervention will mimic the active intervention(s) in every respect except the devices used will be rendered neutral via removal of the pressure threshold spring inside the devices.
arm group label: Sham Training
other name: Sham inspiratory muscle strength training
other name: Sham expiratory muscle strength training
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Richard Berry, M.D.
role: Principal Investigator
affiliation: University of Florida
facility: 
country: United States
responsible party type: Sponsor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
sharing ipd: Undecided