Predictive Accuracy of MATRx Plus in Identifying Favorable Candidates for Oral Appliance Therapy
Condition: Sleep Apnea; Sleep Apnea, Obstructive; Sleep Disordered Breathing
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Interventional

Summary: 
      Obstructive sleep apnea (OSA) is a common disease that is largely un-diagnosed and untreated.
      Standard treatment for obstructive sleep apnea, nasal continuous positive airway pressure
      (CPAP), entails use of a nose mask to deliver positive pressure which dilates the pharynx and
      eliminates obstruction. This therapy is highly efficacious and benign but is associated with
      low adherence, particularly in non-sleepy apneics with disease of mild and moderate severity.
      The principal alternative to CPAP therapy is oral appliance (OA) therapy in which a custom
      made mandibular advancement splint (MAS) is used to protrude the mandible during sleep,
      thereby opening the pharyngeal airway. OA therapy, while preferred and well accepted by most
      participants, is not uniformly efficacious. Additionally, uncertainty regarding the patient's
      response to OAT and the effective target mandibular position can lead to a significant time
      span between diagnosis and initiation of effective treatment. Furthermore, knowledge of the
      effective target mandibular position supports the use of new OA design and manufacturing
      processes that can further reduce the time and cost in delivering the therapy.

      Zephyr Sleep Technologies (the Sponsor) has developed a method of identifying OAT responsive
      participants and their efficacious mandibular protrusion. Recently, Zephyr Sleep Technologies
      developed a portable device that avoids this requirement and can be used in a multi-night
      test in the home. Using a feedback controlled mandibular positioner (FCMP), the device
      measures and analyzes respiratory airflow and oxygen saturation and makes decisions in
      real-time about moving the mandible. The FCMP device was tested in a blinded, bi-phase
      clinical study in which participants with mild-to-severe sleep apnea (n=202) underwent two
      full-night studies in the home. Data from phase 1 were used to develop a predictive method,
      and data from phase 2 were used to prospectively test the accuracy of the predictive method.
      An efficacious mandibular position was also predicted, and each participant was treated with
      a custom oral appliance set to that position. Data from both phases were used to evaluate the
      feasibility of use of the device in the home.

      A random forest machine learning system was used to develop and test the predictive method.
      The overall oral appliance success rate was 76% for phase 1 and 71% for phase 2. The overall
      predictive accuracy was 88%. Values for sensitivity and specificity were 85% and 93%,
      respectively. Positive and negative predictive values were 97% and 72%, respectively. The
      effective target protrusive position was identified in 86% of cases. The studies were
      conducted independently by the participants in their homes, though due to limitations in the
      early prototype design, a clinical coordinator visited the home to set up the equipment prior
      to each night of study. No significant problems were encountered, and no significant risks
      were identified. The results of the clinical trial show that the auto-titrating mandibular
      positioner is suitable for use in the home and accurately predicts OAT outcome as well as
      target protrusive position.

      Based on the results of this study, Zephyr developed a commercially available device which
      has been approved for sale in Canada (Health Canada device license #97614). The device,
      branded MATRx plus, functions as both a sleep recorder as well as a home-based system to
      select patients for oral appliance therapy. This commercially available device is currently
      being used in three separate usability trials to quantify the usability of the device and the
      benefits of an improved workflow through adoption of the new technology in a dental practice.

      Evidence has recently appeared to indicate that the change in pharyngeal volume caused by
      protrusion of the mandible, measured while awake, correlates with the change in
      apnea-hypopnea index (AHI) achieved by OAT, measured while asleep. This is the first
      convincing evidence that an awake measurement of the pharyngeal airway correlates with the
      improvement in respiratory status during sleep induced by an oral appliance. The implication
      is that a simple conebeam CT of the pharynx can predict outcome with OAT. Accordingly, we
      shall carry out conebeam CTs in the research protocol, both at rest position of the mandible
      and at 90% of maximal protrusion.

      The purpose of this study is to test whether the predictive accuracy of the FCMP in the home
      environment is improved by the commercial design and whether patients predicted to be
      suitable for oral appliance therapy have long term adherence.
    

Detailed description: 
      Obstructive sleep apnea (OSA) is a common disease that is largely un-diagnosed and untreated.
      Standard treatment for obstructive sleep apnea, nasal continuous positive airway pressure
      (CPAP), entails use of a nose mask to deliver positive pressure which dilates the pharynx and
      eliminates obstruction. This therapy is highly efficacious and benign but is associated with
      low adherence, particularly in non-sleepy apneics with disease of mild and moderate severity.
      The principal alternative to CPAP therapy is oral appliance (OA) therapy in which a custom
      made mandibular advancement splint (MAS) is used to protrude the mandible during sleep,
      thereby opening the pharyngeal airway. OA therapy, while preferred and well accepted by most
      participants, is not uniformly efficacious. Additionally, uncertainty regarding the patient's
      response to OAT and the effective target mandibular position can lead to a significant time
      span between diagnosis and initiation of effective treatment. Furthermore, knowledge of the
      effective target mandibular position supports the use of new OA design and manufacturing
      processes that can further reduce the time and cost in delivering the therapy.

      Zephyr Sleep Technologies (the Sponsor) has developed a method of identifying OAT responsive
      participants and their efficacious mandibular protrusion. A remotely controlled mandibular
      positioner (RCMP) is used during polysomnographic monitoring to vary the mandibular position.
      The in-lab version of the device, requiring use of a sleep technologist during a
      polysomnographic study, was shown to accurately predict outcome with a custom oral appliance
      in a triple-blind, prospective, predictive study in sixty-seven participants with
      mild-to-severe sleep apnea (specificity: 92%; PPV: 94%; sensitivity: 86%; NPV: 83%). In
      addition, the predicted target mandibular protrusive position proved efficacious in 87.5% of
      cases. While accurate in prospectively identifying oral appliance responders, the
      availability and utility of the RCMP device is limited by the requirement of a
      polysomnographic study.

      Recently, Zephyr Sleep Technologies developed a portable device that avoids this requirement
      and can be used in a multi-night test in the home. Using a feedback controlled mandibular
      positioner (FCMP), the device measures and analyzes respiratory airflow and oxygen saturation
      and makes decisions in real-time about moving the mandible. The FCMP device was tested in a
      blinded, bi-phase clinical study in which participants with mild-to-severe sleep apnea
      (n=202) underwent two full-night studies in the home. Data from phase 1 were used to develop
      a predictive method, and data from phase 2 were used to prospectively test the accuracy of
      the predictive method. An efficacious mandibular position was also predicted, and each
      participant was treated with a custom oral appliance set to that position. Data from both
      phases were used to evaluate the feasibility of use of the device in the home.

      A random forest machine learning system was used to develop and test the predictive method.
      The overall oral appliance success rate was 76% for phase 1 and 71% for phase 2. The overall
      predictive accuracy was 88%. Values for sensitivity and specificity were 85% and 93%,
      respectively. Positive and negative predictive values were 97% and 72%, respectively. The
      effective target protrusive position was identified in 86% of cases. The studies were
      conducted independently by the participants in their homes, though due to limitations in the
      early prototype design, a clinical coordinator visited the home to set up the equipment prior
      to each night of study. No significant problems were encountered, and no significant risks
      were identified. The results of the clinical trial show that the auto-titrating mandibular
      positioner is suitable for use in the home and accurately predicts OAT outcome as well as
      target protrusive position.

      Based on the results of this study, Zephyr developed a commercially available device which
      has been approved for sale in Canada (Health Canada device license #97614). The device,
      branded MATRx plus, functions as both a sleep recorder as well as a home-based system to
      select patients for oral appliance therapy. This commercially available device is currently
      being used in three separate usability trials to quantify the usability of the device and the
      benefits of an improved workflow through adoption of the new technology in a dental practice.

      ProSomnus Sleep Technologies has developed a digitally designed and milled sleep appliance
      called the MicrO2. This device is designed to accurately represent the bite and targeted
      mandibular position, minimize tongue interference, maintain the targeted mandibular position
      throughout the night using 90-degree fin angles and use a novel titration process that can
      reduce error in patient/doctor titration position selection. This device coupled with a
      digital workflow and outcome of the FCMP is postulated to provide an increase in efficiency
      of delivering efficacious treatment to the patient from diagnosis to final therapy.

      Evidence has recently appeared to indicate that the change in velo-pharyngeal volume caused
      by protrusion of the mandible, measured while awake, correlates with the change in
      apnea-hypopnea index (AHI) achieved by OAT, measured while asleep. This is the first
      convincing evidence that an awake measurement of the pharyngeal airway correlates with the
      improvement in respiratory status during sleep induced by an oral appliance. The implication
      is that a simple conebeam CT of the pharynx can predict outcome with OAT. Accordingly, we
      shall carry out conebeam CTs in the research protocol, both at rest position of the mandible
      and at 90% of maximal protrusion.

      The purpose of this study is to test whether the predictive accuracy of the FCMP in the home
      environment is improved by the commercial design and whether patients predicted to be
      suitable for oral appliance therapy have long term adherence.
    

Intervention name(s): MATRx plus
Intervention type(s): Device
Intervention description(s): The MATRx plus test is a 2- or 3-night home sleep test that uses temporary titration trays to move the lower jaw in response to respiratory events. The purpose of the test is to predict oral appliance therapy outcome, and to provide a protrusive position for individuals predicted to experience therapeutic success.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Oral appliance therapy; mandibular protrusion