<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/NCT03835429</url>
  </required_header>
  <id_info>
    <org_study_id>IRB2018-0954</org_study_id>
    <nct_id>NCT03835429</nct_id>
  </id_info>
  <brief_title>Effect of Oral Appliance Therapy on Atrial Fibrillation</brief_title>
  <official_title>Oropharynx-Brainstem-Heart Connection: A Controlled Clinical Trial to Assess Atrial Fibrillation Attenuation in Patients Treated With Oral Appliance Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Texas A&amp;M University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Texas A&amp;M University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot study is expected to determine the efficacy of using the midline traction designed&#xD;
      MyTAP plus mouth shield (MyTAP + MS) oral appliance combination in decreasing the number of&#xD;
      Atrial Fibrillation events. The MS is a patient comfort accessory to the MyTAP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Atrial fibrillation (AF) is highly prevalent in the U.S. and possesses a greater risk in&#xD;
      patients with sleep disordered breathing (SDB) versus patients without SDB. AF recurrence&#xD;
      after catheter ablation is associated with 25% increased risk in patients with obstructive&#xD;
      sleep apnea (OSA). One hypothesis suggests that the repeated hypoxic episodes time-linked to&#xD;
      OSA and central sleep apnea may act as chemo-reflex triggers that enhances brainstem&#xD;
      sympathetic activity in conjunction with responses to OSA-event hypoxia. This hypothesis is&#xD;
      believed to induce tachycardia and cardiovascular stress. In an animal model, episodes of&#xD;
      hypoxia were shown to induce pulmonary vein burst firing and reduction of the negative&#xD;
      tracheal pressure promptly restored normal sinus rhythm. The Trigemino-cardiac reflex&#xD;
      hypothesis implicates chemo- and mechanoreceptors in the oronasal cavity that provides&#xD;
      signaling to the reticular formation via the mesencephalic nucleus of the trigeminal nerve&#xD;
      and serves to control breathing, cardiac function, blood pH (acidity), amongst other body&#xD;
      functions.&#xD;
&#xD;
      The sympathetic system in patients with OSA syndrome is considered to be chronically&#xD;
      hypersensitized. A hyperarousal state suggests AF patients with OSA would tend to have AF&#xD;
      occur more frequently in conjunction with apnea hypopnea events. An increase in autonomic&#xD;
      sympathetic cardiac dominance with a withdrawal of cardiac parasympathetic control could&#xD;
      easily be driven by mechanoreceptors in the oropharynx upon airway narrowing and present as&#xD;
      decreased heart rate variability. Considering that the upper airway is often the site of&#xD;
      greatest airflow restriction (i.e. snoring), a potential sudden rise in autonomic sympathetic&#xD;
      nerve activity in sensory afferent fibers from the oropharynx should be the first to&#xD;
      communicate the airflow reduction to brainstem. This theory is supported by the&#xD;
      investigators' preliminary data and those in other reports. Oral appliance (OA) therapy that&#xD;
      prevents snoring in conjunction with a mouth shield should simultaneously facilitate an open&#xD;
      airway and prevent mouth breathing. The combination effect is expected to decrease vagus&#xD;
      nerve motor efferent activity to the esophagus, facilitate nasal breathing, reduce&#xD;
      sympathetic tone, promote stable sleep and increase HRV(heart rate variability). In patients&#xD;
      with AF, the MyTAP + MS intervention is likely to also facilitate putatively effective&#xD;
      medical therapies, reduce noxious AF triggers, and maintain normal oral bacterial flora&#xD;
      levels and cardiac functioning.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Non-randomized clinical controlled trial design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AF incidence</measure>
    <time_frame>1 month</time_frame>
    <description>Measured (%) incidence of paroxysmal AF episodes &gt;10 seconds in duration, 1-month after starting OA (T1) therapy compared with 1-month prior to using OA.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Periodontal conditions</measure>
    <time_frame>1 month</time_frame>
    <description>Periodontal conditions (defined according to classification developed by Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC-AAP)) 24 assessment at (T0) before MyTAP + MS initiation and after 1-month (T1).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MyTAP advancement change from T1 to T2</measure>
    <time_frame>1 month</time_frame>
    <description>OA advancement in mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate variability analysis after 1 month compared with baseline (T0)</measure>
    <time_frame>1 month</time_frame>
    <description>HRV in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apnea hypopnea index after 1 month (T2) compared with T0-1</measure>
    <time_frame>1 month</time_frame>
    <description>Number of apneas and hypopneas per hour of recording</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygen desaturation index after 1 month (T2) compared with T0-1</measure>
    <time_frame>1 month</time_frame>
    <description>Percent oxygen desaturation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epworth Sleepiness Scale (ESS); Score ≥10 is sleepy, ≥ 18 is very sleepy.</measure>
    <time_frame>1 month</time_frame>
    <description>Change in subjective ESS score pre-OA intervention vs. after 4-weeks of OA use</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>MyTAP oral appliance plus mouth shield</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MyTAP plus mouth shield</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MyTAP oral appliance plus mouth shield</intervention_name>
    <description>The midline traction oral appliance (MyTAP, Airway Management Inc.(AMI), Dallas Texas) is currently marketed as a medical device to treat snoring and obstructive sleep apnea and is FDA cleared.</description>
    <arm_group_label>MyTAP oral appliance plus mouth shield</arm_group_label>
    <other_name>Oral appliance midline traction</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pre-qualified for ablation AF intervention&#xD;
&#xD;
          -  AF &gt; 1 documented episode in a 24-hour electrocardiogram (ECG) Holter examination or&#xD;
             implanted AF monitor in the previous 1 month prior to study enrollment; [AF episode&#xD;
             defined as at least 12 hours duration]&#xD;
&#xD;
          -  At least 8 teeth per arch to support OA device&#xD;
&#xD;
          -  Use of continuous positive air pressure (CPAP)therapy and willingness to switch to OA&#xD;
             use&#xD;
&#xD;
          -  Willing and able to provide verbal and written informed consent&#xD;
&#xD;
          -  Ability to understand how to apply and utilize the sleep recorder and the OA device&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with implantable cardiac rhythm device [pacemakers or internal cardiac device&#xD;
             (ICDs)] or cardiopulmonary disease [heart failure, Chronic obstructive pulmonary&#xD;
             disease (COPD), ventricular dysrhythmia]&#xD;
&#xD;
          -  Unable or unwilling to complete the study demands and schedule&#xD;
&#xD;
          -  Comorbidities of other sleep disorders other than OSA&#xD;
&#xD;
          -  No active temporomandibular joint disorders (TMD) or jaw muscle pain, or morphological&#xD;
             airway abnormalities&#xD;
&#xD;
          -  Pre-existing difficulty swallowing; throat or neck related health issues; endocrine&#xD;
             dysfunction; severe psychiatric and neurological disorders; intellectually disabled;&#xD;
             handicaps limiting sleep position&#xD;
&#xD;
          -  Previous OA therapy or restrictions in jaw opening&#xD;
&#xD;
          -  Prior ablation of AF, myocardial infarction (MI), stroke or decompensation of heart&#xD;
             failure within the last six months, untreated overt hyper- or hypothyroidism&#xD;
&#xD;
          -  Commencement of new anti-arrhythmic drug since last monitor check&#xD;
&#xD;
          -  Pharmacological dependency&#xD;
&#xD;
          -  Concomitant use of hypnotic agents or other sleep aids, nicotine or alcohol intake&#xD;
&#xD;
          -  Mallampati score &gt; III&#xD;
&#xD;
          -  Palatine tonsils - grade &gt; 2&#xD;
&#xD;
          -  History of Uvulopalatopharyngoplasty (UPPP) surgery&#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>Emet Schneiderman, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>TAMHSC</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Emet Schneiderman, PhD</last_name>
    <phone>2148288377</phone>
    <email>emet@tamhsc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Preetam Schramm, PhD</last_name>
    <phone>2148282207</phone>
    <email>schramm@tamhsc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Texas A&amp;M College of Dentistry, Health Science Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emet Schneiderman, PhD</last_name>
      <phone>214-828-8377</phone>
      <email>emet@tamhsc.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>February 6, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>October 9, 2020</last_update_submitted>
  <last_update_submitted_qc>October 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Texas A&amp;M University</investigator_affiliation>
    <investigator_full_name>Emet D. Schneiderman, PhD</investigator_full_name>
    <investigator_title>Professor, Biomedical Sciences</investigator_title>
  </responsible_party>
  <keyword>oral appliance</keyword>
  <keyword>atrial fibrillation</keyword>
  <keyword>sleep apnea</keyword>
  <keyword>mouth shield</keyword>
  <keyword>snoring</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03835429
org study id: IRB2018-0954
nct id: NCT03835429
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
This pilot study is expected to determine the efficacy of using the midline traction designed
      MyTAP plus mouth shield (MyTAP + MS) oral appliance combination in decreasing the number of
      Atrial Fibrillation events. The MS is a patient comfort accessory to the MyTAP.
Atrial fibrillation (AF) is highly prevalent in the U.S. and possesses a greater risk in
      patients with sleep disordered breathing (SDB) versus patients without SDB. AF recurrence
      after catheter ablation is associated with 25% increased risk in patients with obstructive
      sleep apnea (OSA). One hypothesis suggests that the repeated hypoxic episodes time-linked to
      OSA and central sleep apnea may act as chemo-reflex triggers that enhances brainstem
      sympathetic activity in conjunction with responses to OSA-event hypoxia. This hypothesis is
      believed to induce tachycardia and cardiovascular stress. In an animal model, episodes of
      hypoxia were shown to induce pulmonary vein burst firing and reduction of the negative
      tracheal pressure promptly restored normal sinus rhythm. The Trigemino-cardiac reflex
      hypothesis implicates chemo- and mechanoreceptors in the oronasal cavity that provides
      signaling to the reticular formation via the mesencephalic nucleus of the trigeminal nerve
      and serves to control breathing, cardiac function, blood pH (acidity), amongst other body
      functions.

      The sympathetic system in patients with OSA syndrome is considered to be chronically
      hypersensitized. A hyperarousal state suggests AF patients with OSA would tend to have AF
      occur more frequently in conjunction with apnea hypopnea events. An increase in autonomic
      sympathetic cardiac dominance with a withdrawal of cardiac parasympathetic control could
      easily be driven by mechanoreceptors in the oropharynx upon airway narrowing and present as
      decreased heart rate variability. Considering that the upper airway is often the site of
      greatest airflow restriction (i.e. snoring), a potential sudden rise in autonomic sympathetic
      nerve activity in sensory afferent fibers from the oropharynx should be the first to
      communicate the airflow reduction to brainstem. This theory is supported by the
      investigators' preliminary data and those in other reports. Oral appliance (OA) therapy that
      prevents snoring in conjunction with a mouth shield should simultaneously facilitate an open
      airway and prevent mouth breathing. The combination effect is expected to decrease vagus
      nerve motor efferent activity to the esophagus, facilitate nasal breathing, reduce
      sympathetic tone, promote stable sleep and increase HRV(heart rate variability). In patients
      with AF, the MyTAP + MS intervention is likely to also facilitate putatively effective
      medical therapies, reduce noxious AF triggers, and maintain normal oral bacterial flora
      levels and cardiac functioning.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Non-randomized clinical controlled trial design
primary purpose: Treatment
masking: None (Open Label)
measure: AF incidence
time frame: 1 month
description: Measured (%) incidence of paroxysmal AF episodes >10 seconds in duration, 1-month after starting OA (T1) therapy compared with 1-month prior to using OA.
measure: Periodontal conditions
time frame: 1 month
description: Periodontal conditions (defined according to classification developed by Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC-AAP)) 24 assessment at (T0) before MyTAP + MS initiation and after 1-month (T1).
measure: MyTAP advancement change from T1 to T2
time frame: 1 month
description: OA advancement in mm
measure: Heart rate variability analysis after 1 month compared with baseline (T0)
time frame: 1 month
description: HRV in ms
measure: Apnea hypopnea index after 1 month (T2) compared with T0-1
time frame: 1 month
description: Number of apneas and hypopneas per hour of recording
measure: Oxygen desaturation index after 1 month (T2) compared with T0-1
time frame: 1 month
description: Percent oxygen desaturation
measure: Epworth Sleepiness Scale (ESS); Score ≥10 is sleepy, ≥ 18 is very sleepy.
time frame: 1 month
description: Change in subjective ESS score pre-OA intervention vs. after 4-weeks of OA use
arm group label: MyTAP oral appliance plus mouth shield
arm group type: Experimental
description: MyTAP plus mouth shield
intervention type: Device
intervention name: MyTAP oral appliance plus mouth shield
description: The midline traction oral appliance (MyTAP, Airway Management Inc.(AMI), Dallas Texas) is currently marketed as a medical device to treat snoring and obstructive sleep apnea and is FDA cleared.
arm group label: MyTAP oral appliance plus mouth shield
other name: Oral appliance midline traction
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emet Schneiderman, PhD
role: Principal Investigator
affiliation: TAMHSC
last name: Emet Schneiderman, PhD
phone: 2148288377
email: emet@tamhsc.edu
last name: Preetam Schramm, PhD
phone: 2148282207
email: schramm@tamhsc.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Texas A&M University
investigator full name: Emet D. Schneiderman, PhD
investigator title: Professor, Biomedical Sciences
mesh term: Atrial Fibrillation
sharing ipd: No