<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/NCT04438785</url>
  </required_header>
  <id_info>
    <org_study_id>90694424</org_study_id>
    <nct_id>NCT04438785</nct_id>
  </id_info>
  <brief_title>Effects of Myofunctional Therapy With an Application in Severe Apnea/Hypopnea Sleep Obstructive Syndrome (MTASSAOS)</brief_title>
  <acronym>MTASSAOS</acronym>
  <official_title>Effects of Myofunctional Therapy With an M-health Application Airway Gym in Severe Apnea/Hypopnea Sleep Obstructive Syndrome: A Randomized Multicentre Control Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Quironsalud</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Quironsalud</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>
      • Background and study aims: Obstructive sleep apnea is a potentially serious sleep disorder.&#xD;
      It causes breathing to stop and start repeatedly during sleep. There are several types of&#xD;
      sleep apnea, the most common of which is obstructive sleep apnea. This type of apnea occurs&#xD;
      when an individual's throat muscles intermittently relax and block the airway during sleep.&#xD;
&#xD;
      The classic treatment for this disease is based on weight loss, and exercise, and the use of&#xD;
      a continuous positive airway pressure (CPAP) machine.&#xD;
&#xD;
      Myofunctional therapy (MT) is one of the newest treatments for sleep-disordered breathing. MT&#xD;
      is based on daily exercises of the throat muscles in an attempt to strengthen them and&#xD;
      facilitate opening of the airway.&#xD;
&#xD;
      Who can participate? Patients diagnosed with severe sleep apnea and aged between 18-75 years.&#xD;
&#xD;
      What does the study involve? Participants will be randomly allocated to either use of the&#xD;
      &quot;AirwayGym&quot; smartphone app or no treatment for 3 months. The AirwayGym app provides&#xD;
      instructions on how to perform exercises to strengthen the throat muscles and reminds&#xD;
      participants to perform the exercises for 20 min per day. Participants will be assessed&#xD;
      monthly at the clinic.&#xD;
&#xD;
      What are the possible benefits and risks of participating? Benefits: Curing sleep apnea&#xD;
      syndrome. There are no significant risks for participants.&#xD;
&#xD;
      Where is the study run from? Hospital Quirónsalud Marbella (Spain) When is the study starting&#xD;
      and how long is it expected to run for? October 2018 to January 2021 Who is funding the&#xD;
      study? Investigator initiated and funded Who is the main contact? Dr. Carlos O'Connor Reina,&#xD;
      coconnor@us.es&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      INTRODUCTION Obstructive sleep apnea/hypopnea syndrome (OSAHS) has become one of the more&#xD;
      serious health problems worldwide (Mendes et al., 2014). Because of its relationship with&#xD;
      obesity, its prevalence and incidence have increased. It is associated with morbidities such&#xD;
      as cardiovascular and cerebrovascular diseases. The classic treatment of this disease is&#xD;
      based on dietary measures, weight loss, and exercise, and the use of a continuous positive&#xD;
      airway pressure (CPAP) machine.&#xD;
&#xD;
      Myofunctional therapy (MT) is one of the newest treatments for sleep-disordered breathing&#xD;
      (Camacho et al., 2015). MT is based on daily exercises using the oropharyngeal muscles in an&#xD;
      attempt to strength them and facilitate opening of the airway. OSAHS originates from the&#xD;
      suboptimal function of the dilator muscles of the airway. Therefore, MT is a therapy designed&#xD;
      theoretically to deal with the underlying mechanism of this disease (Korhan et al., 2015). MT&#xD;
      is based on oropharyngeal exercises described by diagrams, videos, and weekly instructions&#xD;
      from a myofunctional therapist. The patient is instructed to perform the exercises regularly,&#xD;
      for at least 3 months, and for 30 min daily. In some cases, patients perform exercises by&#xD;
      themselves at home without substantial feedback and without giving precise information to the&#xD;
      therapist about their performance of the exercises (O'Connor et al., 2019).&#xD;
&#xD;
      Most existing mobile health (mHealth) apps for OSAHS focus on diagnosis of snoring or OSAHS&#xD;
      (Isetta et al., 2017), while a few are designed to promote adherence to treatment with CPAP&#xD;
      (Camacho et al., 2015). To our knowledge, there are no apps that focus on the treatment of&#xD;
      OSAHS. However, mobile technology could be especially valuable in treating OSAHS patients&#xD;
      because of its potential to promote patient empowerment and self-management (Iftikhar et al.,&#xD;
      2017).&#xD;
&#xD;
      One of the best treatments for OSAHS is exercise and weight loss (Iftikhar et al., 2018).&#xD;
      Because patients' time is limited, the investigators consider that there will be a greater&#xD;
      probability of their performing the exercises if they are able to do wherever and whatever.&#xD;
      Therefore, the investigators designed and developed a novel mHealth app to promote&#xD;
      oropharyngeal exercises while interacting with a smartphone. In this prospective randomized&#xD;
      multicenter clinical trial, the investigators aim to evaluate adherence to the app and its&#xD;
      effectiveness in a group of patients (AirwayGym group, AGG) with severe OSAHS compared with a&#xD;
      control group (CG) of similar patients.&#xD;
&#xD;
      HYPOTHESIS The regular use of the AirwayGym app, which is designed to perform and increase&#xD;
      adherence to MT, will improve OSAHS in patients with severe disease ,apnea hypopnea index&#xD;
      (AHI)&gt;30) by increasing the tone of their upper airway muscles.&#xD;
&#xD;
      OBJECTIVES The main objective will be to study the evolution of the use of the app based on&#xD;
      MT in patients diagnosed with severe OSAHS.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        1. To evaluate the influence of MT using an app on the change in the AHI in patients&#xD;
           diagnosed with severe OSAHS.&#xD;
&#xD;
        2. To evaluate O2 nadir and O2 desaturation index.&#xD;
&#xD;
        3. To use scores obtained using the Iowa Oral Performance Instrument (IOPI) to evaluate the&#xD;
           tone of genioglossus and buccinator muscles.&#xD;
&#xD;
        4. To evaluate subjective morning somnolence and sleep quality score using the Epworth&#xD;
           Sleepiness Scale and Pittsburgh Sleep Quality Index.&#xD;
&#xD;
      METHODS Design: Prospective controlled quasi-experimental clinical trial in patients with&#xD;
      severe OSAHS (AHI&gt;30). Study population: Patients recently diagnosed with severe OSAHS who&#xD;
      agree to participate in this clinical trial.&#xD;
&#xD;
      Evaluation of the effectiveness of use of the app in performing MT in patients with severe&#xD;
      OSAHS will be performed using the longitudinal values obtained during study, based on the&#xD;
      percentage of improvement in the AHI observed during follow-up. This percentage has been&#xD;
      calculated from results reported in previous MT studies published and presented in the&#xD;
      bibliography. To achieve a confidence level of 95% and power of 80% with an estimated&#xD;
      improvement of the AHI of 60%, the required sample size is 30 patients (15 AirwayGym group&#xD;
      [AGG], 15 CG).&#xD;
&#xD;
      Randomization will be based on the consecutive order of patient enrollment, with odd numbers&#xD;
      allocated to the AGG (patients treated with the app) and even numbers to the CG (patients&#xD;
      without complementary therapy).&#xD;
&#xD;
      Patients without a smartphone will be directly recruited to the CG. VARIABLES EVALUATED: Age,&#xD;
      sex, weight, height, body mass index (BMI), waist circumference (belly button height), neck&#xD;
      circumference, IOPI lingual and buccinator, AHI, O2 desaturation index, and O2 nadir.&#xD;
&#xD;
      Questionnaires: Friedman stage, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index&#xD;
      PROCEDURE The AGG will use the app, which was created in a collaboration between the Sleep&#xD;
      Units of Hospital Quirónsalud Marbella and Campo de Gibraltar. The novelty of this app is&#xD;
      that it is the first in the healthcare market in which the patient can interact directly with&#xD;
      the smartphone; the phone provides acoustic feedback about the efficacy of the exercises&#xD;
      performed and is focused on sleep apnea disease and improving proprioceptive deficits. The&#xD;
      app includes nine exercises based on MT that attempt to enhance the tonicity of the various&#xD;
      muscles involved in the pathogenesis of OSAHS. Before every exercise, an animated&#xD;
      demonstration and a video show the patient how to perform the exercise. At the conclusion of&#xD;
      each exercise, the patient receives feedback about the success of their performance via a&#xD;
      point score. When the patient finishes the exercises, they are saved in the cloud and a&#xD;
      therapist can evaluate the performance of them. A chat function is available where patient&#xD;
      can contact the therapist.&#xD;
&#xD;
      This app complies with regulation 2002/58/Community European (CE) and (UE) 2016/679&#xD;
      concerning data protection.&#xD;
&#xD;
      The main objective of these exercises is to increase the tone of the extrinsic muscles of the&#xD;
      tongue.&#xD;
&#xD;
      The exercises are based on those described elsewhere (Guimaraes et al., 2009), adapted to&#xD;
      obtain feedback with the phone and to stimulate proprioceptive sensors with acoustic&#xD;
      feedback.&#xD;
&#xD;
      For hygiene reasons, it is recommended that participants cover the screen with cling film&#xD;
      during all exercises.&#xD;
&#xD;
      The CG does not use any therapy for OSAHS for 3 months. All patients will attend hospital&#xD;
      once a month for measurement of the variables (weight, height, BMI, neck and waist&#xD;
      circumference, completion of the questionnaires, IOPI scores)&#xD;
&#xD;
      Schedule of visits:&#xD;
&#xD;
      SELECTION VISIT Patients with newly diagnosed severe OSAHS based on home or laboratory&#xD;
      polygraphy with measures of AHI, O2 saturation, and O2 nadir were evaluated. All sleep&#xD;
      studies were manually interpreted by a sleep technician according to the standard criteria of&#xD;
      the American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated&#xD;
      Events, and were reviewed by certified physicians. Information about inclusion and exclusion&#xD;
      criteria, evaluation of the type of smartphone used, previous experience with the app, and&#xD;
      the study protocol was provided. After any questions were resolved, the patient agreed to&#xD;
      participate and signed informed consent (IC).&#xD;
&#xD;
      INITIAL VISIT Participants were evaluated by an Ear nose and throat (ENT) specialist and&#xD;
      underwent pharyngoscopy, rhinofibrolaryngoscopy, Friedman staging, Marchesani protocol, and&#xD;
      examination of their temporomandibular joint dysfunction. If the patient presented with&#xD;
      tonsillitis grade IV, complete nose obstruction, ankyloglossia, or problems with&#xD;
      temporomandibular joint dysfunction, they were excluded from the study.&#xD;
&#xD;
      SECOND VISIT: Variables were measured (weight, height, BMI, neck and waist circumference,&#xD;
      completion of questionnaires, IOPI scores) and randomization was performed to AGG or CG.&#xD;
      Participants in the AGG were instructed about the use of the app and the exercises to do.&#xD;
&#xD;
      FOLLOW-UP VISITS:&#xD;
&#xD;
      AGG: Participants performed exercises daily for about 20 min. Follow-up visits occurred after&#xD;
      1 month (visit 3) and 3 months (visit 4). At these visits, variables were measured,&#xD;
      questionnaires completed, and exercise performance checked.&#xD;
&#xD;
      CG: Follow-up visits occurred after 1 month (visit 3) and 3 months (visit 4). At these&#xD;
      visits, variables were measured, questionnaires completed, and it was checked that no other&#xD;
      therapies are being followed.&#xD;
&#xD;
      Final visit: At 3 months for both groups. At this visit, questionnaires were completed,&#xD;
      variables were measured again, and laboratory or in-home polygraphy was performed. The total&#xD;
      study duration for each participant was 3 months.&#xD;
&#xD;
      DISCONTINUATION CRITERIA&#xD;
&#xD;
      A participant in either group was excluded from the study if:&#xD;
&#xD;
        1. They did not perform exercises during at least 85% of the scheduled sessions,or were&#xD;
           lost to follow-up because they did not attend hospital visits.&#xD;
&#xD;
        2. They lost 5% of their body weight during study participation. Data were collected in a&#xD;
           database. Nominal variables were described by their frequency distribution. Quantitative&#xD;
           variables were assessed by calculating the arithmetic mean and standard deviation.&#xD;
           Baseline characteristics of the two groups of participants with OSAHS were compared by&#xD;
           two-tailed paired t tests for continuous variables and chi-squared or Fisher's exact&#xD;
           test for nominal variables. For variables with skewed distribution, the investigators&#xD;
           performed Mann-Whitney tests. In addition, the investigators performed Pearson&#xD;
           correlation analysis of changes in AHI compared with changes in possible explanatory&#xD;
           variables, including BMI and neck and waist circumference. A P value less than 0.05 was&#xD;
           considered significant.&#xD;
&#xD;
      The main outcome measures are polygraphy findings at the beginning and end of the study, IOPI&#xD;
      scores at the beginning and end of the study, Epworth Sleepiness Scale and Pittsburgh Sleep&#xD;
      Quality Index at all visits, weight in kg, height in cm, BMI in kg/m2, and neck and waist&#xD;
      circumference in cm at all visits.&#xD;
&#xD;
      ETHICAL APPROVAL After evaluating and revising the protocol, the Investigation Ethical&#xD;
      Committee (EC) from Costa del Sol approved the study with the code AWGAPN-2019-01. Before&#xD;
      starting the trial, all participants had to have signed and dated all IC approved by the EC.&#xD;
&#xD;
      Access to data and data protection. To ensure confidentiality of study data, the original&#xD;
      data were stored in the Hospital and only the investigators and the Investigation EC had&#xD;
      access.&#xD;
&#xD;
      UTILITY This app could improve participants' AHI and quality of life and reduce their&#xD;
      clinical symptoms and need for treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 18, 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>Parallel Assignment</intervention_model>
    <intervention_model_description>Interventional prospective multicentre trial with consecutive random assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Results will be analysed blinded by the investigators.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Apnea Hypopnea Index (AHI)</measure>
    <time_frame>Baseline and three months</time_frame>
    <description>Measurement of number of apneas or hypopneas recorded during the study per hour of sleep</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of O2 Desaturation Index (ODI)</measure>
    <time_frame>Baseline and three months</time_frame>
    <description>The ODI is the number of times per hour of sleep that the blood oxygen level drops by a certain degree from baseline. Any respiratory event during sleep with a 3% drop in blood oxygen levels is counted towards the total. For example, a change from 95% to 92% would be an event that is counted toward the index's total.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of Iowa Oral Performance Instrument (IOPI) Score</measure>
    <time_frame>Baseline and three months</time_frame>
    <description>The IOPI objectively measures maximum tongue strength in kilopascals and represents the tone of the genioglossus muscles.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iowa Oral Performance Instrument Lip Strength</measure>
    <time_frame>Baseline and three months</time_frame>
    <description>The IOPI objectively measures maximum lip strength in kilopascals and represents the tone of the buccinator muscles.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neck Circumference (cm)</measure>
    <time_frame>Baseline and three months.</time_frame>
    <description>Gives an idea if there is an anatomical change or reduction in fat in the upper airway muscles after intervention .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waist Circumference (cm)</measure>
    <time_frame>Baseline and three months</time_frame>
    <description>Gives an idea if there is an anatomical change or reduction of fat in the thorax muscles after intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Mass Index BMI</measure>
    <time_frame>Baseline and three months</time_frame>
    <description>is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass in kilograms divided by the square of the body height in meters, and is expressed in units kg/m^2 .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epworth Sleepiness Scale</measure>
    <time_frame>Baseline and three months</time_frame>
    <description>A scale (0-24), obtained by self-administered questionnaire, that rates an individual's probability of falling asleep on a scale of increasing probability from 0 to 3 for eight different situations that people experience in their daily lives.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pittsburgh Sleep Quality Index</measure>
    <time_frame>Baseline and three months</time_frame>
    <description>A scale (0- 21) obtained by a self-report questionnaire that assesses sleep quality over a 1-month time interval. The questionnaire consists of a combination of Likerttype and open-ended questions (later converted to scaled scores using provided guidelines).&#xD;
Respondents are asked to indicate how frequently they have experienced certain sleep difficulties over the past month and to rate their overall sleep quality. Scores for each question range from 0 to 3, with higher scores indicating more acute sleep disturbances.A global score of 5 or more indicates poor sleep quality and that the higher the score, the worse the quality of sleep. The questionnaire consists of 19 individual items, creating seven components that produce one global score, and takes 5-10 min to complete.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Obstructive Sleep Apnea-hypopnea Syndrome</condition>
  <arm_group>
    <arm_group_label>INTERVENTION (AirwayGym) GROUP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CONTROL GROUP</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>The intervention consists of myofunctional therapy (MT) using the AirwayGym app.</intervention_name>
    <description>Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
    <arm_group_label>INTERVENTION (AirwayGym) GROUP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18-75 years&#xD;
&#xD;
          -  Recently diagnosed with severe sleep apnea and do not have any previous experience or&#xD;
             information with this pathology&#xD;
&#xD;
          -  Consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI &gt; 40 kg/m²&#xD;
&#xD;
          -  Inability to fill up questionnaires&#xD;
&#xD;
          -  Severe drug or alcohol abuse&#xD;
&#xD;
          -  Hypnotic medication&#xD;
&#xD;
          -  Not controlled coronary disease&#xD;
&#xD;
          -  Decompensated Heart failure&#xD;
&#xD;
          -  Stroke&#xD;
&#xD;
          -  Systemic Disease associated with inflammatory diagnosed entity (arthritis,&#xD;
             sarcoidosis, vasculitis, lupus…)&#xD;
&#xD;
          -  Neuromuscular disease (like Duchenne)&#xD;
&#xD;
          -  Craniofacial deformities.&#xD;
&#xD;
          -  Active oncologic process.&#xD;
&#xD;
          -  Any antecedents of MT treatment or other treatment for sleep apnea could affect study&#xD;
             results of the study (surgery, Mandibular Advancement Device (MAD) or CPAP).&#xD;
&#xD;
        Once the patient accepted and signed consent and met inclusion criteria, they will be&#xD;
        attended by Ent specialist to rule out:&#xD;
&#xD;
          -  Severe upper airway obstruction (Complete nose obstruction, Tonsils grade IV/IV )&#xD;
&#xD;
          -  Presence of tongue tie (Marchesani protocol) with limitation of tongue movements&#xD;
&#xD;
          -  Antecedents or presence of temporomandibular joint disorders&#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>JOSE MARIA IGNACIO GARCIA, MD</last_name>
    <role>Study Chair</role>
    <affiliation>NEUMOLOGY DEPARMENT HOSPITAL QUIRONSALUD MARBELLA</affiliation>
  </overall_official>
  <overall_official>
    <last_name>FRANCISCO JESUS GONZALEZ SANCHEZPharm D, Pharm D</last_name>
    <role>Study Director</role>
    <affiliation>RESEARCH UNIT HOSPITAL QUIRONSALUD MARBELLA</affiliation>
  </overall_official>
  <overall_official>
    <last_name>CARLOS O´CONNOR REINA, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>OTOLARINGOLOGY DEPARMENT HOSPITAL QUIRONSALUD MARBELLA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Quironsalud Campo de Gibraltar</name>
      <address>
        <city>Los Barrios</city>
        <state>Cadiz</state>
        <zip>11379</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Quironsalud Marbella</name>
      <address>
        <city>Marbella</city>
        <state>Malaga</state>
        <zip>29603</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Mendes FA, Marone SA, Duarte BB, Arenas AC. Epidemiologic profile of patients with snoring and obstructive sleep apnea in a university hospital. Int Arch Otorhinolaryngol. 2014 Apr;18(2):142-5. doi: 10.1055/s-0033-1359309. Epub 2014 Feb 28.</citation>
    <PMID>25992080</PMID>
  </reference>
  <reference>
    <citation>Camacho M, Certal V, Abdullatif J, Zaghi S, Ruoff CM, Capasso R, Kushida CA. Myofunctional Therapy to Treat Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. Sleep. 2015 May 1;38(5):669-75. doi: 10.5665/sleep.4652.</citation>
    <PMID>25348130</PMID>
  </reference>
  <reference>
    <citation>Korhan I, Gode S, Midilli R, Basoglu OK. The influence of the lateral pharyngeal wall anatomy on snoring and sleep apnoea. J Pak Med Assoc. 2015 Feb;65(2):125-30.</citation>
    <PMID>25842544</PMID>
  </reference>
  <reference>
    <citation>Isetta V, Torres M, Gonzalez K, Ruiz C, Dalmases M, Embid C, Navajas D, Farre R, Montserrat JM. A New mHealth application to support treatment of sleep apnoea patients. J Telemed Telecare. 2017 Jan;23(1):14-18. doi: 10.1177/1357633X15621848. Epub 2016 Jul 8.</citation>
    <PMID>26672606</PMID>
  </reference>
  <reference>
    <citation>Camacho M, Robertson M, Abdullatif J, Certal V, Kram YA, Ruoff CM, Brietzke SE, Capasso R. Smartphone apps for snoring. J Laryngol Otol. 2015 Oct;129(10):974-9. doi: 10.1017/S0022215115001978. Epub 2015 Sep 3.</citation>
    <PMID>26333720</PMID>
  </reference>
  <reference>
    <citation>Iftikhar IH, Bittencourt L, Youngstedt SD, Ayas N, Cistulli P, Schwab R, Durkin MW, Magalang UJ. Comparative efficacy of CPAP, MADs, exercise-training, and dietary weight loss for sleep apnea: a network meta-analysis. Sleep Med. 2017 Feb;30:7-14. doi: 10.1016/j.sleep.2016.06.001. Epub 2016 Jun 28.</citation>
    <PMID>28215266</PMID>
  </reference>
  <reference>
    <citation>Iftikhar IH, Roland J. Obesity Hypoventilation Syndrome. Clin Chest Med. 2018 Jun;39(2):427-436. doi: 10.1016/j.ccm.2018.01.006.</citation>
    <PMID>29779600</PMID>
  </reference>
  <results_reference>
    <citation>O'Connor Reina C, Plaza Mayor G, Ignacio-Garcia JM, Baptista Jardin P, Garcia-Iriarte MT, Casado-Morente JC. Floppy Closing Door Epiglottis Treated Successfully with an Mhealth Application Based on Myofunctional Therapy: A Case Report. Case Rep Otolaryngol. 2019 Jul 1;2019:4157898. doi: 10.1155/2019/4157898. eCollection 2019.</citation>
    <PMID>31355035</PMID>
  </results_reference>
  <results_reference>
    <citation>O'Connor-Reina C, Ignacio Garcia JM, Rodriguez Ruiz E, Morillo Dominguez MDC, Ignacio Barrios V, Baptista Jardin P, Casado Morente JC, Garcia Iriarte MT, Plaza G. Myofunctional Therapy App for Severe Apnea-Hypopnea Sleep Obstructive Syndrome: Pilot Randomized Controlled Trial. JMIR Mhealth Uhealth. 2020 Nov 9;8(11):e23123. doi: 10.2196/23123.</citation>
    <PMID>33093013</PMID>
  </results_reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <results_first_submitted>November 6, 2020</results_first_submitted>
  <results_first_submitted_qc>December 21, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 15, 2021</results_first_posted>
  <last_update_submitted>January 27, 2021</last_update_submitted>
  <last_update_submitted_qc>January 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SEVERE OSAHS</keyword>
  <keyword>MYOFUNTIONAL THERAPY</keyword>
  <keyword>M HEALTH APPLICATION</keyword>
  <keyword>TELEMEDICINE</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The datasets generated during and/or analysed during the current study are not expected to be made available due to confidentiality</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT04438785/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>INTERVENTION (AirwayGym) GROUP</title>
          <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
        </group>
        <group group_id="P2">
          <title>CONTROL GROUP</title>
          <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>change of weight, give up intervention</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>INTERVENTION (AirwayGym) GROUP</title>
          <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
        </group>
        <group group_id="B2">
          <title>CONTROL GROUP</title>
          <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</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="10"/>
            <count group_id="B3" value="28"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.17" lower_limit="56.4" upper_limit="71.3"/>
                    <measurement group_id="B2" value="63.9" lower_limit="53.7" upper_limit="64.6"/>
                    <measurement group_id="B3" value="62.2" lower_limit="54.5" upper_limit="68.9"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>IOPI tongue strength (is the maximun strength obtained by contraction of genioglossus muscle)</title>
          <units>kilopascals</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39.83" lower_limit="35.32" upper_limit="45.2"/>
                    <measurement group_id="B2" value="42" lower_limit="32.6" upper_limit="51.3"/>
                    <measurement group_id="B3" value="41.3" lower_limit="33.3" upper_limit="49.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>IOPI Lip Strength (maximal lip strength measured with muscle buccinator)</title>
          <units>kilopascals</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.8" lower_limit="24.1" upper_limit="32.4"/>
                    <measurement group_id="B2" value="28.1" lower_limit="23.7" upper_limit="32.5"/>
                    <measurement group_id="B3" value="27.95" lower_limit="23.9" upper_limit="32.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Apnea Hypopnea Index (AHI)</title>
        <description>Measurement of number of apneas or hypopneas recorded during the study per hour of sleep</description>
        <time_frame>Baseline and three months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>INTERVENTION (AirwayGym) GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
          </group>
          <group group_id="O2">
            <title>CONTROL GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Apnea Hypopnea Index (AHI)</title>
          <description>Measurement of number of apneas or hypopneas recorded during the study per hour of sleep</description>
          <units>events per 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="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Apnea Hypopnea Index (BASELINE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.77" lower_limit="33.84" upper_limit="55.69"/>
                    <measurement group_id="O2" value="47.36" lower_limit="38.59" upper_limit="56.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Apnea Hypopnea Index(AFTER 3 MONTHS)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.88" lower_limit="14.02" upper_limit="27.74"/>
                    <measurement group_id="O2" value="35" lower_limit="31.2" upper_limit="38.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Evaluate if the Apnea Hypopnea Index from Baseline and after three months in the Intervention Group showed statistical significant difference p&lt;0.05 .</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>2.58</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Evaluation of O2 Desaturation Index (ODI)</title>
        <description>The ODI is the number of times per hour of sleep that the blood oxygen level drops by a certain degree from baseline. Any respiratory event during sleep with a 3% drop in blood oxygen levels is counted towards the total. For example, a change from 95% to 92% would be an event that is counted toward the index's total.</description>
        <time_frame>Baseline and three months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>INTERVENTION (AirwayGym) GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
          </group>
          <group group_id="O2">
            <title>CONTROL GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of O2 Desaturation Index (ODI)</title>
          <description>The ODI is the number of times per hour of sleep that the blood oxygen level drops by a certain degree from baseline. Any respiratory event during sleep with a 3% drop in blood oxygen levels is counted towards the total. For example, a change from 95% to 92% would be an event that is counted toward the index's total.</description>
          <units>events per 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="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ODI (BASELINE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.31" lower_limit="27.19" upper_limit="43.43"/>
                    <measurement group_id="O2" value="40.64" lower_limit="29.46" upper_limit="51.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ODI (AFTER 3 MONTHS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.4" lower_limit="12.9" upper_limit="25.98"/>
                    <measurement group_id="O2" value="32.03" lower_limit="24.14" upper_limit="39.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Evaluate if the O2 desaturation index (ODI) from Baseline and after three months in the Intervention Group showed statistical significant difference p&lt;0.05 .</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-0.971</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Evaluation of Iowa Oral Performance Instrument (IOPI) Score</title>
        <description>The IOPI objectively measures maximum tongue strength in kilopascals and represents the tone of the genioglossus muscles.</description>
        <time_frame>Baseline and three months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>INTERVENTION (AirwayGym) GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
          </group>
          <group group_id="O2">
            <title>CONTROL GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of Iowa Oral Performance Instrument (IOPI) Score</title>
          <description>The IOPI objectively measures maximum tongue strength in kilopascals and represents the tone of the genioglossus muscles.</description>
          <units>Kilopascals</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="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.1" lower_limit="39.5" upper_limit="48.8"/>
                    <measurement group_id="O2" value="31.3" lower_limit="26.6" upper_limit="35.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Evaluate if the IOPI tongue score from baseline and after three months in the Intervention Group showed statistical significant difference p&lt;0.05 .</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.364</param_value>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Iowa Oral Performance Instrument Lip Strength</title>
        <description>The IOPI objectively measures maximum lip strength in kilopascals and represents the tone of the buccinator muscles.</description>
        <time_frame>Baseline and three months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>INTERVENTION (AirwayGym) GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
          </group>
          <group group_id="O2">
            <title>CONTROL GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Iowa Oral Performance Instrument Lip Strength</title>
          <description>The IOPI objectively measures maximum lip strength in kilopascals and represents the tone of the buccinator muscles.</description>
          <units>kilopascals</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="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IOPI Lip BASELINE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.89" lower_limit="24.16" upper_limit="32.47"/>
                    <measurement group_id="O2" value="28.1" lower_limit="23.7" upper_limit="32.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IOPI Lip AFTER 3 MONTHS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.11" lower_limit="39.5" upper_limit="48.8"/>
                    <measurement group_id="O2" value="31.3" lower_limit="26.6" upper_limit="35.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Evaluate if the IOPI lip score from the baseline and after three months in the Intervention Group showed statistical significant difference p&lt;0.05 .</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-1.131</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neck Circumference (cm)</title>
        <description>Gives an idea if there is an anatomical change or reduction in fat in the upper airway muscles after intervention .</description>
        <time_frame>Baseline and three months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>INTERVENTION (AirwayGym) GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
          </group>
          <group group_id="O2">
            <title>CONTROL GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Neck Circumference (cm)</title>
          <description>Gives an idea if there is an anatomical change or reduction in fat in the upper airway muscles after intervention .</description>
          <units>centimetres</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="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Neck Circumference BASE LINE (CM)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.7" lower_limit="41.03" upper_limit="46.4"/>
                    <measurement group_id="O2" value="43.7" lower_limit="40.33" upper_limit="46.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neck Circumference 3 MONTHS (CM)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.6" lower_limit="42.12" upper_limit="47.2"/>
                    <measurement group_id="O2" value="43.5" lower_limit="40.33" upper_limit="46.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Evaluate if the neck circumference from Baseline and after three months in the Intervention Group showed statistical significant difference p&lt;0.05 .</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.92</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.98</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Waist Circumference (cm)</title>
        <description>Gives an idea if there is an anatomical change or reduction of fat in the thorax muscles after intervention.</description>
        <time_frame>Baseline and three months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>INTERVENTION (AirwayGym) GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
          </group>
          <group group_id="O2">
            <title>CONTROL GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Waist Circumference (cm)</title>
          <description>Gives an idea if there is an anatomical change or reduction of fat in the thorax muscles after intervention.</description>
          <units>centimetres</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="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Waist circumference baseline (cm)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109.2" lower_limit="102.9" upper_limit="115.4"/>
                    <measurement group_id="O2" value="109.1" lower_limit="97.5" upper_limit="120.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Waist circumference after 3 months (cm)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108.84" lower_limit="102.9" upper_limit="115.4"/>
                    <measurement group_id="O2" value="108.5" lower_limit="96.9" upper_limit="120.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Evaluate if the waist circumference from baseline and after three months in the Intervention Group showed statistical significant difference p&lt;0.05 .</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.92</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.98</param_value>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Body Mass Index BMI</title>
        <description>is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass in kilograms divided by the square of the body height in meters, and is expressed in units kg/m^2 .</description>
        <time_frame>Baseline and three months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>INTERVENTION (AirwayGym) GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
          </group>
          <group group_id="O2">
            <title>CONTROL GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Body Mass Index BMI</title>
          <description>is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass in kilograms divided by the square of the body height in meters, and is expressed in units kg/m^2 .</description>
          <units>kilograms/m^2</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="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>BMI BASELINE kg/m^2 .</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.9" lower_limit="26.8" upper_limit="31.02"/>
                    <measurement group_id="O2" value="29.6" lower_limit="27.1" upper_limit="32.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BMI AFTER 3 MONTHS kg/m^2 .</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.8" lower_limit="26.7" upper_limit="30.8"/>
                    <measurement group_id="O2" value="29.6" lower_limit="27.3" upper_limit="31.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Evaluate if the BMI from Baseline and after three months in the Intervention Group showed statistical significant difference p&lt;0.05 .</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.98</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.97</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Epworth Sleepiness Scale</title>
        <description>A scale (0-24), obtained by self-administered questionnaire, that rates an individual's probability of falling asleep on a scale of increasing probability from 0 to 3 for eight different situations that people experience in their daily lives.</description>
        <time_frame>Baseline and three months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>INTERVENTION (AirwayGym) GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
          </group>
          <group group_id="O2">
            <title>CONTROL GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Epworth Sleepiness Scale</title>
          <description>A scale (0-24), obtained by self-administered questionnaire, that rates an individual's probability of falling asleep on a scale of increasing probability from 0 to 3 for eight different situations that people experience in their daily lives.</description>
          <units>score 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="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Epworth sleepiness scales (Baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.3" lower_limit="8.71" upper_limit="12.24"/>
                    <measurement group_id="O2" value="9.3" lower_limit="6.6" upper_limit="12.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Epworth sleepiness scales (Three months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3" lower_limit="3.45" upper_limit="7.2"/>
                    <measurement group_id="O2" value="9.6" lower_limit="6.8" upper_limit="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Evaluate if the Epworth Sleepiness Scale from Baseline and after three months in the Intervention Group showed statistical significant difference p&lt;0.05 .</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-1.23</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pittsburgh Sleep Quality Index</title>
        <description>A scale (0- 21) obtained by a self-report questionnaire that assesses sleep quality over a 1-month time interval. The questionnaire consists of a combination of Likerttype and open-ended questions (later converted to scaled scores using provided guidelines).&#xD;
Respondents are asked to indicate how frequently they have experienced certain sleep difficulties over the past month and to rate their overall sleep quality. Scores for each question range from 0 to 3, with higher scores indicating more acute sleep disturbances.A global score of 5 or more indicates poor sleep quality and that the higher the score, the worse the quality of sleep. The questionnaire consists of 19 individual items, creating seven components that produce one global score, and takes 5-10 min to complete.</description>
        <time_frame>Baseline and three months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>INTERVENTION (AirwayGym) GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
          </group>
          <group group_id="O2">
            <title>CONTROL GROUP</title>
            <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Pittsburgh Sleep Quality Index</title>
          <description>A scale (0- 21) obtained by a self-report questionnaire that assesses sleep quality over a 1-month time interval. The questionnaire consists of a combination of Likerttype and open-ended questions (later converted to scaled scores using provided guidelines).&#xD;
Respondents are asked to indicate how frequently they have experienced certain sleep difficulties over the past month and to rate their overall sleep quality. Scores for each question range from 0 to 3, with higher scores indicating more acute sleep disturbances.A global score of 5 or more indicates poor sleep quality and that the higher the score, the worse the quality of sleep. The questionnaire consists of 19 individual items, creating seven components that produce one global score, and takes 5-10 min to complete.</description>
          <units>score 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="18"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pittsburgh sleep quality index (Baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.2" lower_limit="8.22" upper_limit="12.0"/>
                    <measurement group_id="O2" value="8.8" lower_limit="7.1" upper_limit="10.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pittsburgh sleep quality index (Three Months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.3" lower_limit="8.71" upper_limit="12.2"/>
                    <measurement group_id="O2" value="9.78" lower_limit="7.2" upper_limit="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Evaluate if the Pittsburgh sleep quality index from Baseline and after three months in the Intervention Group showed statistical significant difference p&lt;0.05 .</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.22</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.98</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected during the performance of the study 3 months</time_frame>
      <desc>The definition of adverse event did not differ from Adverse Event definition. Event collection was done through daily telemedicine approach.</desc>
      <group_list>
        <group group_id="E1">
          <title>INTERVENTION (AirwayGym) GROUP</title>
          <description>Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.&#xD;
The intervention consists of myofunctional therapy (MT) using the AirwayGym app.: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.</description>
        </group>
        <group group_id="E2">
          <title>CONTROL GROUP</title>
          <description>Patients newly diagnosed with severe OSAHS do no therapy for 90 days.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <limitations_and_caveats>In the end, we had a small sample recruited mainly due to Covid restrictions. We have a significant loss of patients in the control group (50%) due the severity of the disease and the need of therapy. Initially we start to perform polysomnographies but we change to polygraphies due to hospital needs during pandemia.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Francisco Jesus Gonzalez</name_or_title>
      <organization>Grupo Hospitalario Quironsalud</organization>
      <phone>0034645014593</phone>
      <email>fgonzasan@gmail.com</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/NCT04438785
org study id: 90694424
nct id: NCT04438785
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
• Background and study aims: Obstructive sleep apnea is a potentially serious sleep disorder.
      It causes breathing to stop and start repeatedly during sleep. There are several types of
      sleep apnea, the most common of which is obstructive sleep apnea. This type of apnea occurs
      when an individual's throat muscles intermittently relax and block the airway during sleep.

      The classic treatment for this disease is based on weight loss, and exercise, and the use of
      a continuous positive airway pressure (CPAP) machine.

      Myofunctional therapy (MT) is one of the newest treatments for sleep-disordered breathing. MT
      is based on daily exercises of the throat muscles in an attempt to strengthen them and
      facilitate opening of the airway.

      Who can participate? Patients diagnosed with severe sleep apnea and aged between 18-75 years.

      What does the study involve? Participants will be randomly allocated to either use of the
      "AirwayGym" smartphone app or no treatment for 3 months. The AirwayGym app provides
      instructions on how to perform exercises to strengthen the throat muscles and reminds
      participants to perform the exercises for 20 min per day. Participants will be assessed
      monthly at the clinic.

      What are the possible benefits and risks of participating? Benefits: Curing sleep apnea
      syndrome. There are no significant risks for participants.

      Where is the study run from? Hospital Quirónsalud Marbella (Spain) When is the study starting
      and how long is it expected to run for? October 2018 to January 2021 Who is funding the
      study? Investigator initiated and funded Who is the main contact? Dr. Carlos O'Connor Reina,
      coconnor@us.es
INTRODUCTION Obstructive sleep apnea/hypopnea syndrome (OSAHS) has become one of the more
      serious health problems worldwide (Mendes et al., 2014). Because of its relationship with
      obesity, its prevalence and incidence have increased. It is associated with morbidities such
      as cardiovascular and cerebrovascular diseases. The classic treatment of this disease is
      based on dietary measures, weight loss, and exercise, and the use of a continuous positive
      airway pressure (CPAP) machine.

      Myofunctional therapy (MT) is one of the newest treatments for sleep-disordered breathing
      (Camacho et al., 2015). MT is based on daily exercises using the oropharyngeal muscles in an
      attempt to strength them and facilitate opening of the airway. OSAHS originates from the
      suboptimal function of the dilator muscles of the airway. Therefore, MT is a therapy designed
      theoretically to deal with the underlying mechanism of this disease (Korhan et al., 2015). MT
      is based on oropharyngeal exercises described by diagrams, videos, and weekly instructions
      from a myofunctional therapist. The patient is instructed to perform the exercises regularly,
      for at least 3 months, and for 30 min daily. In some cases, patients perform exercises by
      themselves at home without substantial feedback and without giving precise information to the
      therapist about their performance of the exercises (O'Connor et al., 2019).

      Most existing mobile health (mHealth) apps for OSAHS focus on diagnosis of snoring or OSAHS
      (Isetta et al., 2017), while a few are designed to promote adherence to treatment with CPAP
      (Camacho et al., 2015). To our knowledge, there are no apps that focus on the treatment of
      OSAHS. However, mobile technology could be especially valuable in treating OSAHS patients
      because of its potential to promote patient empowerment and self-management (Iftikhar et al.,
      2017).

      One of the best treatments for OSAHS is exercise and weight loss (Iftikhar et al., 2018).
      Because patients' time is limited, the investigators consider that there will be a greater
      probability of their performing the exercises if they are able to do wherever and whatever.
      Therefore, the investigators designed and developed a novel mHealth app to promote
      oropharyngeal exercises while interacting with a smartphone. In this prospective randomized
      multicenter clinical trial, the investigators aim to evaluate adherence to the app and its
      effectiveness in a group of patients (AirwayGym group, AGG) with severe OSAHS compared with a
      control group (CG) of similar patients.

      HYPOTHESIS The regular use of the AirwayGym app, which is designed to perform and increase
      adherence to MT, will improve OSAHS in patients with severe disease ,apnea hypopnea index
      (AHI)>30) by increasing the tone of their upper airway muscles.

      OBJECTIVES The main objective will be to study the evolution of the use of the app based on
      MT in patients diagnosed with severe OSAHS.

      Secondary Objectives:

        1. To evaluate the influence of MT using an app on the change in the AHI in patients
           diagnosed with severe OSAHS.

        2. To evaluate O2 nadir and O2 desaturation index.

        3. To use scores obtained using the Iowa Oral Performance Instrument (IOPI) to evaluate the
           tone of genioglossus and buccinator muscles.

        4. To evaluate subjective morning somnolence and sleep quality score using the Epworth
           Sleepiness Scale and Pittsburgh Sleep Quality Index.

      METHODS Design: Prospective controlled quasi-experimental clinical trial in patients with
      severe OSAHS (AHI>30). Study population: Patients recently diagnosed with severe OSAHS who
      agree to participate in this clinical trial.

      Evaluation of the effectiveness of use of the app in performing MT in patients with severe
      OSAHS will be performed using the longitudinal values obtained during study, based on the
      percentage of improvement in the AHI observed during follow-up. This percentage has been
      calculated from results reported in previous MT studies published and presented in the
      bibliography. To achieve a confidence level of 95% and power of 80% with an estimated
      improvement of the AHI of 60%, the required sample size is 30 patients (15 AirwayGym group
      [AGG], 15 CG).

      Randomization will be based on the consecutive order of patient enrollment, with odd numbers
      allocated to the AGG (patients treated with the app) and even numbers to the CG (patients
      without complementary therapy).

      Patients without a smartphone will be directly recruited to the CG. VARIABLES EVALUATED: Age,
      sex, weight, height, body mass index (BMI), waist circumference (belly button height), neck
      circumference, IOPI lingual and buccinator, AHI, O2 desaturation index, and O2 nadir.

      Questionnaires: Friedman stage, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index
      PROCEDURE The AGG will use the app, which was created in a collaboration between the Sleep
      Units of Hospital Quirónsalud Marbella and Campo de Gibraltar. The novelty of this app is
      that it is the first in the healthcare market in which the patient can interact directly with
      the smartphone; the phone provides acoustic feedback about the efficacy of the exercises
      performed and is focused on sleep apnea disease and improving proprioceptive deficits. The
      app includes nine exercises based on MT that attempt to enhance the tonicity of the various
      muscles involved in the pathogenesis of OSAHS. Before every exercise, an animated
      demonstration and a video show the patient how to perform the exercise. At the conclusion of
      each exercise, the patient receives feedback about the success of their performance via a
      point score. When the patient finishes the exercises, they are saved in the cloud and a
      therapist can evaluate the performance of them. A chat function is available where patient
      can contact the therapist.

      This app complies with regulation 2002/58/Community European (CE) and (UE) 2016/679
      concerning data protection.

      The main objective of these exercises is to increase the tone of the extrinsic muscles of the
      tongue.

      The exercises are based on those described elsewhere (Guimaraes et al., 2009), adapted to
      obtain feedback with the phone and to stimulate proprioceptive sensors with acoustic
      feedback.

      For hygiene reasons, it is recommended that participants cover the screen with cling film
      during all exercises.

      The CG does not use any therapy for OSAHS for 3 months. All patients will attend hospital
      once a month for measurement of the variables (weight, height, BMI, neck and waist
      circumference, completion of the questionnaires, IOPI scores)

      Schedule of visits:

      SELECTION VISIT Patients with newly diagnosed severe OSAHS based on home or laboratory
      polygraphy with measures of AHI, O2 saturation, and O2 nadir were evaluated. All sleep
      studies were manually interpreted by a sleep technician according to the standard criteria of
      the American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated
      Events, and were reviewed by certified physicians. Information about inclusion and exclusion
      criteria, evaluation of the type of smartphone used, previous experience with the app, and
      the study protocol was provided. After any questions were resolved, the patient agreed to
      participate and signed informed consent (IC).

      INITIAL VISIT Participants were evaluated by an Ear nose and throat (ENT) specialist and
      underwent pharyngoscopy, rhinofibrolaryngoscopy, Friedman staging, Marchesani protocol, and
      examination of their temporomandibular joint dysfunction. If the patient presented with
      tonsillitis grade IV, complete nose obstruction, ankyloglossia, or problems with
      temporomandibular joint dysfunction, they were excluded from the study.

      SECOND VISIT: Variables were measured (weight, height, BMI, neck and waist circumference,
      completion of questionnaires, IOPI scores) and randomization was performed to AGG or CG.
      Participants in the AGG were instructed about the use of the app and the exercises to do.

      FOLLOW-UP VISITS:

      AGG: Participants performed exercises daily for about 20 min. Follow-up visits occurred after
      1 month (visit 3) and 3 months (visit 4). At these visits, variables were measured,
      questionnaires completed, and exercise performance checked.

      CG: Follow-up visits occurred after 1 month (visit 3) and 3 months (visit 4). At these
      visits, variables were measured, questionnaires completed, and it was checked that no other
      therapies are being followed.

      Final visit: At 3 months for both groups. At this visit, questionnaires were completed,
      variables were measured again, and laboratory or in-home polygraphy was performed. The total
      study duration for each participant was 3 months.

      DISCONTINUATION CRITERIA

      A participant in either group was excluded from the study if:

        1. They did not perform exercises during at least 85% of the scheduled sessions,or were
           lost to follow-up because they did not attend hospital visits.

        2. They lost 5% of their body weight during study participation. Data were collected in a
           database. Nominal variables were described by their frequency distribution. Quantitative
           variables were assessed by calculating the arithmetic mean and standard deviation.
           Baseline characteristics of the two groups of participants with OSAHS were compared by
           two-tailed paired t tests for continuous variables and chi-squared or Fisher's exact
           test for nominal variables. For variables with skewed distribution, the investigators
           performed Mann-Whitney tests. In addition, the investigators performed Pearson
           correlation analysis of changes in AHI compared with changes in possible explanatory
           variables, including BMI and neck and waist circumference. A P value less than 0.05 was
           considered significant.

      The main outcome measures are polygraphy findings at the beginning and end of the study, IOPI
      scores at the beginning and end of the study, Epworth Sleepiness Scale and Pittsburgh Sleep
      Quality Index at all visits, weight in kg, height in cm, BMI in kg/m2, and neck and waist
      circumference in cm at all visits.

      ETHICAL APPROVAL After evaluating and revising the protocol, the Investigation Ethical
      Committee (EC) from Costa del Sol approved the study with the code AWGAPN-2019-01. Before
      starting the trial, all participants had to have signed and dated all IC approved by the EC.

      Access to data and data protection. To ensure confidentiality of study data, the original
      data were stored in the Hospital and only the investigators and the Investigation EC had
      access.

      UTILITY This app could improve participants' AHI and quality of life and reduce their
      clinical symptoms and need for treatment.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Interventional prospective multicentre trial with consecutive random assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Results will be analysed blinded by the investigators.
measure: Apnea Hypopnea Index (AHI)
time frame: Baseline and three months
description: Measurement of number of apneas or hypopneas recorded during the study per hour of sleep
measure: Evaluation of O2 Desaturation Index (ODI)
time frame: Baseline and three months
description: The ODI is the number of times per hour of sleep that the blood oxygen level drops by a certain degree from baseline. Any respiratory event during sleep with a 3% drop in blood oxygen levels is counted towards the total. For example, a change from 95% to 92% would be an event that is counted toward the index's total.
measure: Evaluation of Iowa Oral Performance Instrument (IOPI) Score
time frame: Baseline and three months
description: The IOPI objectively measures maximum tongue strength in kilopascals and represents the tone of the genioglossus muscles.
measure: Iowa Oral Performance Instrument Lip Strength
time frame: Baseline and three months
description: The IOPI objectively measures maximum lip strength in kilopascals and represents the tone of the buccinator muscles.
measure: Neck Circumference (cm)
time frame: Baseline and three months.
description: Gives an idea if there is an anatomical change or reduction in fat in the upper airway muscles after intervention .
measure: Waist Circumference (cm)
time frame: Baseline and three months
description: Gives an idea if there is an anatomical change or reduction of fat in the thorax muscles after intervention.
measure: Body Mass Index BMI
time frame: Baseline and three months
description: is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass in kilograms divided by the square of the body height in meters, and is expressed in units kg/m^2 .
measure: Epworth Sleepiness Scale
time frame: Baseline and three months
description: A scale (0-24), obtained by self-administered questionnaire, that rates an individual's probability of falling asleep on a scale of increasing probability from 0 to 3 for eight different situations that people experience in their daily lives.
measure: Pittsburgh Sleep Quality Index
time frame: Baseline and three months
description: A scale (0- 21) obtained by a self-report questionnaire that assesses sleep quality over a 1-month time interval. The questionnaire consists of a combination of Likerttype and open-ended questions (later converted to scaled scores using provided guidelines).
Respondents are asked to indicate how frequently they have experienced certain sleep difficulties over the past month and to rate their overall sleep quality. Scores for each question range from 0 to 3, with higher scores indicating more acute sleep disturbances.A global score of 5 or more indicates poor sleep quality and that the higher the score, the worse the quality of sleep. The questionnaire consists of 19 individual items, creating seven components that produce one global score, and takes 5-10 min to complete.
arm group label: INTERVENTION (AirwayGym) GROUP
arm group type: Experimental
description: Patients newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the AirwayGym app for 20 min a day for 90 days.
arm group label: CONTROL GROUP
arm group type: No Intervention
description: Patients newly diagnosed with severe OSAHS do no therapy for 90 days.
intervention type: Device
intervention name: The intervention consists of myofunctional therapy (MT) using the AirwayGym app.
description: Intervention. Patient newly diagnosed with severe OSAHS should perform muscle upper airway exercises using the App AirwayGym 20 minutes a day during 90 days.
arm group label: INTERVENTION (AirwayGym) GROUP
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: JOSE MARIA IGNACIO GARCIA, MD
role: Study Chair
affiliation: NEUMOLOGY DEPARMENT HOSPITAL QUIRONSALUD MARBELLA
last name: FRANCISCO JESUS GONZALEZ SANCHEZPharm D, Pharm D
role: Study Director
affiliation: RESEARCH UNIT HOSPITAL QUIRONSALUD MARBELLA
last name: CARLOS O´CONNOR REINA, MD
role: Principal Investigator
affiliation: OTOLARINGOLOGY DEPARMENT HOSPITAL QUIRONSALUD MARBELLA
facility: 
facility: 
country: Spain
citation: Mendes FA, Marone SA, Duarte BB, Arenas AC. Epidemiologic profile of patients with snoring and obstructive sleep apnea in a university hospital. Int Arch Otorhinolaryngol. 2014 Apr;18(2):142-5. doi: 10.1055/s-0033-1359309. Epub 2014 Feb 28.
PMID: 25992080
citation: Camacho M, Certal V, Abdullatif J, Zaghi S, Ruoff CM, Capasso R, Kushida CA. Myofunctional Therapy to Treat Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. Sleep. 2015 May 1;38(5):669-75. doi: 10.5665/sleep.4652.
PMID: 25348130
citation: Korhan I, Gode S, Midilli R, Basoglu OK. The influence of the lateral pharyngeal wall anatomy on snoring and sleep apnoea. J Pak Med Assoc. 2015 Feb;65(2):125-30.
PMID: 25842544
citation: Isetta V, Torres M, Gonzalez K, Ruiz C, Dalmases M, Embid C, Navajas D, Farre R, Montserrat JM. A New mHealth application to support treatment of sleep apnoea patients. J Telemed Telecare. 2017 Jan;23(1):14-18. doi: 10.1177/1357633X15621848. Epub 2016 Jul 8.
PMID: 26672606
citation: Camacho M, Robertson M, Abdullatif J, Certal V, Kram YA, Ruoff CM, Brietzke SE, Capasso R. Smartphone apps for snoring. J Laryngol Otol. 2015 Oct;129(10):974-9. doi: 10.1017/S0022215115001978. Epub 2015 Sep 3.
PMID: 26333720
citation: Iftikhar IH, Bittencourt L, Youngstedt SD, Ayas N, Cistulli P, Schwab R, Durkin MW, Magalang UJ. Comparative efficacy of CPAP, MADs, exercise-training, and dietary weight loss for sleep apnea: a network meta-analysis. Sleep Med. 2017 Feb;30:7-14. doi: 10.1016/j.sleep.2016.06.001. Epub 2016 Jun 28.
PMID: 28215266
citation: Iftikhar IH, Roland J. Obesity Hypoventilation Syndrome. Clin Chest Med. 2018 Jun;39(2):427-436. doi: 10.1016/j.ccm.2018.01.006.
PMID: 29779600
citation: O'Connor Reina C, Plaza Mayor G, Ignacio-Garcia JM, Baptista Jardin P, Garcia-Iriarte MT, Casado-Morente JC. Floppy Closing Door Epiglottis Treated Successfully with an Mhealth Application Based on Myofunctional Therapy: A Case Report. Case Rep Otolaryngol. 2019 Jul 1;2019:4157898. doi: 10.1155/2019/4157898. eCollection 2019.
PMID: 31355035
citation: O'Connor-Reina C, Ignacio Garcia JM, Rodriguez Ruiz E, Morillo Dominguez MDC, Ignacio Barrios V, Baptista Jardin P, Casado Morente JC, Garcia Iriarte MT, Plaza G. Myofunctional Therapy App for Severe Apnea-Hypopnea Sleep Obstructive Syndrome: Pilot Randomized Controlled Trial. JMIR Mhealth Uhealth. 2020 Nov 9;8(11):e23123. doi: 10.2196/23123.
PMID: 33093013
responsible party type: Sponsor
mesh term: Apnea
mesh term: Sleep Apnea, Obstructive
mesh term: Syndrome
sharing ipd: No
ipd description: The datasets generated during and/or analysed during the current study are not expected to be made available due to confidentiality
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: In the end, we had a small sample recruited mainly due to Covid restrictions. We have a significant loss of patients in the control group (50%) due the severity of the disease and the need of therapy. Initially we start to perform polysomnographies but we change to polygraphies due to hospital needs during pandemia.
point of contact: 