<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/NCT02261857</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00078727</org_study_id>
    <nct_id>NCT02261857</nct_id>
  </id_info>
  <brief_title>3D-Printed CPAP Masks for Children With Obstructive Sleep Apnea</brief_title>
  <official_title>Personalized Three-Dimensionally Printed CPAP Masks for Obstructive Sleep Apnea Therapy in Children With Craniofacial Anomalies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Glenn Green</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>American Academy of Otolaryngology-Head and Neck Surgery Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether patient-specific computer-aided design&#xD;
      (CAD) and three-dimensional (3D) printing can be utilized to produce personalized, effective&#xD;
      continuous positive airway pressure (CPAP) masks for children with severe obstructive sleep&#xD;
      apnea (OSA) and craniofacial anomalies who encounter significant difficulty using CPAP&#xD;
      because of poorly fitting masks despite exhausting available commercial mask options.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obstructive sleep apnea (OSA) is a common problem in the general pediatric population,&#xD;
      generally cited as between 1-5%, with morbidity ranging from daytime behavioral problems and&#xD;
      inattention to cardiopulmonary effects including hypertension and ventricular hypertrophy.&#xD;
      OSA is dramatically more prevalent among children with certain craniofacial anomalies and&#xD;
      syndromes (e.g. Pierre-Robin, Treacher Collins, etc.), generally because of small, short&#xD;
      jaws, midface hypoplasia, and/or disproportionally large tongues . While tonsillectomy and&#xD;
      adenoidectomy is considered first line therapy for OSA in the general pediatric population,&#xD;
      children with OSA due to craniofacial anomalies frequently require more aggressive&#xD;
      intervention to improve their breathing at night, which often includes continuous positive&#xD;
      airway pressure ventilation (CPAP). Most children who require CPAP therapy are able to find a&#xD;
      mask that will adequately seal while providing acceptable comfort, however a small percentage&#xD;
      of children encounter significant difficulty finding a functional CPAP interface, most often&#xD;
      because of dysmorphic facial features. This can prove a significant barrier to effective CPAP&#xD;
      therapy and lead to frustration on the part of patients' caregivers and providers, as well as&#xD;
      the associated morbidity of untreated severe OSA. The purpose of this feasibility study is to&#xD;
      investigate the use of patient-specific computational design and three-dimensional (3D)&#xD;
      printing to produce personalized CPAP masks for children intolerant of standard CPAP masks&#xD;
      due to poor fit secondary to craniofacial anomalies who encounter significant difficulty&#xD;
      using CPAP because of poorly fitting masks despite exhausting available commercial mask&#xD;
      options.&#xD;
&#xD;
      Study Design&#xD;
&#xD;
      This will be a prospective case study examining the feasibility of using patient-specific CAD&#xD;
      and 3D printing technology to produce personalized CPAP masks for children intolerant of&#xD;
      commercially available masks due to poor fit. Patients will be recruited from the pediatric&#xD;
      otolaryngology, pediatric oral maxillofacial surgery, and pediatric sleep clinics at the&#xD;
      University of Michigan Medical Center, with a target cohort of five.&#xD;
&#xD;
      Only patients of study team members will be included in the study, and no recruitment will&#xD;
      take place outside the clinics of participating study team members. We anticipate the study&#xD;
      period to last 3 years, though it may terminate sooner if recruitment targets are reached&#xD;
      expeditiously.&#xD;
&#xD;
      After recruitment and consent of a potential study subject, each subject will undergo an&#xD;
      initial mask-design evaluation with members of the research team. At this initial visit, the&#xD;
      following will be performed:&#xD;
&#xD;
        1. A head &amp; neck physical exam, which a focus on characteristics important for treatment of&#xD;
           OSA (e.g. jaw size and position, tongue size and position, characteristics of palate,&#xD;
           presence or absence of cleft, external nasal deformity, external or internal nasal&#xD;
           valvular collapse)&#xD;
&#xD;
        2. Review of patient's photographs&#xD;
&#xD;
        3. Generation of a topographic model of the patient's facial anatomy utilizing the 3dMDface&#xD;
           system (specifics below) which will be export as a Stereolithography (.STL) file.&#xD;
&#xD;
      The patient's facial .STL file will then be imported into a computer-aided design (CAD)&#xD;
      modeling program (MimicsTM or MagicsTM, Materialise, Belgium). Contact points along the&#xD;
      topographic model are drawn out and utilized for modeling of the custom mask. The custom mask&#xD;
      model is then exported in .STL format for import into the 3D printer for fabrication using a&#xD;
      fused-deposition modeling (FDM) method (Object Pro, Stratasys, Israel).&#xD;
&#xD;
      Once the mask has been fabricated, patients will undergo a mask-fit evaluation. If a mask&#xD;
      appears to fit well, the patient will use it at home with home CPAP for one month of&#xD;
      consistent use. They will then return for debriefing and re-evaluation, with subsequent&#xD;
      iterations of mask design as needed. If the mask functions for the patient better than any&#xD;
      other alternatives, the patient will be allowed to continue to use the mask for up to one&#xD;
      year, with ongoing surveillance by the research team, assessing for mask durability and&#xD;
      ongoing usage/compliance.&#xD;
&#xD;
      Data collection will include:&#xD;
&#xD;
        -  Objective data regarding the nature of each patient's obstructive sleep apnea and CPAP&#xD;
           pressure requirements sleep-disordered breathing from the most recent available&#xD;
           polysomnograms (sleep study, abbreviated PSG)&#xD;
&#xD;
        -  Information regarding all prior CPAP masks attempted&#xD;
&#xD;
        -  One month compliance data downloads from CPAP machines - with both the prior &quot;best&#xD;
           alternative&quot; if usable, and with the customized mask, including percentage of days used,&#xD;
           average hours usage, residual apnea-hypopnea index (AHI) and time spent in large leak&#xD;
           per night.&#xD;
&#xD;
        -  Standardized interview with patients and their parents regarding other masks used and&#xD;
           experience with the customized mask(s).&#xD;
&#xD;
        -  Descriptive anatomic information regarding facial anomalies contributing to poor mask&#xD;
           fit, obtained from physical exam, photographs, and imaging studies.&#xD;
&#xD;
        -  Validated quality of life measures taken before and at completion of trial period with&#xD;
           customized CPAP mask, including the Pediatric Sleep Questionnaire (PSQ) and the OSA-18 ,&#xD;
           to assess the impact of successful CPAP use for our patients.&#xD;
&#xD;
      Analysis will involve basic descriptive statistics to describe both the objective outcomes&#xD;
      (e.g. compliance data from CPAP machines) and quality of life measures (PSQ and OSA-18&#xD;
      surveys) as well as information on individual experiences collected during interviews.&#xD;
&#xD;
      Additional Data on 3D Photography System&#xD;
&#xD;
      Patient facial modeling information will be obtained utilizing a 3dMDface system (3dMD,&#xD;
      Atlanta, GA). The 3dMD system is a three-dimensional photography system which generates a&#xD;
      three-dimensional model of the patient's face utilizing multiple convergent cameras (see&#xD;
      Figure 1 below). The three-dimensional model is generated utilizing hybrid&#xD;
      stereophotogrammetry, with software algorithms using both projected random patterns and&#xD;
      texture of the skin (pores, freckles, etc.) to stereo-triangulate and generate a 3D surface&#xD;
      image. The 3D model of the patient's face is created within the 3dMDvultus software system,&#xD;
      which can then export the model in .STL format. No patient identifying information is stored&#xD;
      within the .STL file.&#xD;
&#xD;
      All 3D photography sessions with study subjects will be performed or supervised by one of the&#xD;
      members of the study team. There will be no cost associated with using the 3dMDface system.&#xD;
      Utilizing 3D photography allows us to obtain the most time-accurate topographic information&#xD;
      of the patient's face while avoiding the cost and risk associated with conventional CT or MRI&#xD;
      imaging.&#xD;
&#xD;
      Data Included in Registry:&#xD;
&#xD;
        -  Pre- and post- intervention OSA-18 and PSQ questionnaire aggregates. Data to be recorded&#xD;
           includes: sum score and mean score for each questionnaire.&#xD;
&#xD;
        -  Pre-intervention AHI and oxygen saturation (SpO2) nadir based on most recent sleep PSG.&#xD;
&#xD;
        -  Pre-intervention CPAP requirements based on most recent CPAP titration PSG.&#xD;
&#xD;
        -  Pre-intervention compliance data downloads from subject's CPAP machines from prior 1&#xD;
           month's use. Data to be recorded includes: percentage of days used, average hours usage,&#xD;
           residual apnea-hypopnea index (AHI), size of leak in liters per minute, and time spent&#xD;
           in large leak per night.&#xD;
&#xD;
        -  Post-intervention compliance data downloads from subject's CPAP machines from prior 1&#xD;
           month's use. Data to be recorded includes: percentage of days used, average hours usage,&#xD;
           residual apnea-hypopnea index (AHI), size of leak in liters per minute, and time spent&#xD;
           in large leak per night.&#xD;
&#xD;
      Data Registry QA:&#xD;
&#xD;
      • Physical and electronic PDF versions of each data registry primary source (questionnaires,&#xD;
      polysomnograms, and CPAP compliance reports) will be kept for the 5 years past the duration&#xD;
      of the study. Data uploaded to the patient registry will be verified with the institutional&#xD;
      IRB.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2013</start_date>
  <completion_date type="Actual">September 2017</completion_date>
  <primary_completion_date type="Actual">September 2017</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in CPAP Compliance at 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Subject CPAP usage data will be downloaded from their CPAP machine before beginning the use to personalized mask (baseline) and after 1 month of consistent use of the personalized mask (1 month post-intervention). Average hours usage will be recorded and compared between baseline CPAP usage data and 1 month post-intervention CPAP usage data to assess efficacy of the personalized mask compared to the best prior alternative. Outcome will be measured as a numerical value in hours per night.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in CPAP Leak Rate at 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Subject CPAP usage data will be downloaded from their CPAP machine before beginning the use to personalized mask (baseline) and after 1 month of consistent use of the personalized mask (1 month post-intervention). Leak in liters per minute will be recorded and compared between baseline CPAP usage data and 1 month post-intervention CPAP usage data to assess efficacy of the personalized mask compared to the best prior alternative. Outcome will be measured as a numerical value in liters per minute.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in residual AHI on CPAP at 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Subject CPAP usage data will be downloaded from their CPAP machine before beginning the use to personalized mask (baseline) and after 1 month of consistent use of the personalized mask (1 month post-intervention). Residual apnea-hypopnea index (AHI) will be recorded and compared between baseline CPAP usage data and 1 month post-intervention CPAP usage data to assess efficacy of the personalized mask compared to the best prior alternative. Outcome will be measured as a numerical value denoting AHI.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in time spent in large leak on CPAP at 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Subject CPAP usage data will be downloaded from their CPAP machine before beginning the use to personalized mask (baseline) and after 1 month of consistent use of the personalized mask (1 month post-intervention). Percentage (%) time spent in large leak per night will be recorded and compared between baseline CPAP usage data and 1 month post-intervention CPAP usage data to assess efficacy of the personalized mask compared to the best prior alternative. Outcome will be measured as a numerical percentage as a percentage of total time spent in large leak per night over total time using CPAP per night.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life via OSA-18 questionnaire</measure>
    <time_frame>1 month</time_frame>
    <description>Subject's parents or legal guardians will complete OSA-18 questionnaire (validated OSA quality of of life questionnaires) pre-intervention (baseline) and at 1-month post-intervention. These will be compared to assess effect on quality of life of the interventional device. Outcome will be measured as a numerical value as sum of all question value responses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcomes: Comfort at baseline</measure>
    <time_frame>Baseline</time_frame>
    <description>Subjects will be assessed clinically when first wearing the interventional device to ensure there are no issues with device fit, comfort, or undue forces on the face. Outcome will be measured as a binary numerical value with 0 denoting no issues with comfort and 1 denoting issues with comfort.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcomes: Comfort at 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Subjects will be assessed clinically after using the personalized mask consistently for 1 month at home to ensure there are no issues with device fit, comfort or undue forces on the face. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with comfort and 1 denoting issues with comfort.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcomes: Skin reaction at 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Subjects will be assessed clinically after using the personalized mask consistently for 1 month at home to ensure there are no issues with skin reaction or breakdown on the face. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with skin reaction and 1 denoting issues with skin reaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life via PSQ questionnaire</measure>
    <time_frame>1 month</time_frame>
    <description>Subject's parents or legal guardians will complete PSQ questionnaire (validated OSA quality of of life questionnaires) pre-intervention (baseline) and at 1-month post-intervention. These will be compared to assess effect on quality of life of the interventional device. Outcome will be measured as a numerical value as sum of all question value responses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcomes: durability at 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Subjects will be assessed clinically after using the personalized mask consistently for 1 month at home to ensure there are no issues with excessive wear or tear of the personalized mask. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with durability and 1 denoting issues with durability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcomes: Skin reaction at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Subjects will be assessed clinically after using the personalized mask consistently for 12 months at home to ensure there are no issues with skin reaction or breakdown on the face. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with skin reaction and 1 denoting issues with skin reaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcomes: Durability at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Subjects will be assessed clinically after using the personalized mask consistently for 12 months at home to ensure there are no issues with excessive wear or tear of the personalized mask. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with durability and 1 denoting issues with durability.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Sleep Apnea, Obstructive</condition>
  <condition>Craniofacial Abnormalities</condition>
  <condition>Pediatric Disorder</condition>
  <arm_group>
    <arm_group_label>Intervention Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention: Subjects will undergo assessment and a personalized CPAP mask device will be manufactured using patient-specific computer-aided design and 3D printing. The subject will use the personalized CPAP mask for 1 month of consistent use and post-intervention data will be collected for compare to historical control (see other arm)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Historical Control Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Pre-interventional baseline data on subject OSA, CPAP compliance, and quality of life (QoL) measures will be collected to serve as historical controls.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Personalized continuous positive airway pressure (CPAP) mask</intervention_name>
    <description>Personalized CPAP mask manufactured for study subjects using a combination of patient-specific computer-aided design and three-dimensional printing</description>
    <arm_group_label>Intervention Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  On-going need for CPAP therapy based on polysomnography&#xD;
&#xD;
          -  Inability to tolerate CPAP attributed to poor fit by a sleep clinician&#xD;
&#xD;
          -  The opinion of a sleep clinician that reasonable commercially available mask options&#xD;
             have been exhausted&#xD;
&#xD;
          -  Caregivers must also be proficient in English to complete standard questionnaires.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects no longer needing CPAP therapy&#xD;
&#xD;
          -  Subjects able to successfully use a commercially available mask.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Glenn E Green, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Marcus CL, Brooks LJ, Draper KA, Gozal D, Halbower AC, Jones J, Schechter MS, Ward SD, Sheldon SH, Shiffman RN, Lehmann C, Spruyt K; American Academy of Pediatrics. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2012 Sep;130(3):e714-55. doi: 10.1542/peds.2012-1672. Epub 2012 Aug 27.</citation>
    <PMID>22926176</PMID>
  </reference>
  <reference>
    <citation>Brunetti L, Rana S, Lospalluti ML, Pietrafesa A, Francavilla R, Fanelli M, Armenio L. Prevalence of obstructive sleep apnea syndrome in a cohort of 1,207 children of southern Italy. Chest. 2001 Dec;120(6):1930-5. doi: 10.1378/chest.120.6.1930.</citation>
    <PMID>11742924</PMID>
  </reference>
  <reference>
    <citation>Amin RS, Kimball TR, Bean JA, Jeffries JL, Willging JP, Cotton RT, Witt SA, Glascock BJ, Daniels SR. Left ventricular hypertrophy and abnormal ventricular geometry in children and adolescents with obstructive sleep apnea. Am J Respir Crit Care Med. 2002 May 15;165(10):1395-9. doi: 10.1164/rccm.2105118.</citation>
    <PMID>12016102</PMID>
  </reference>
  <reference>
    <citation>Duman D, Naiboglu B, Esen HS, Toros SZ, Demirtunc R. Impaired right ventricular function in adenotonsillar hypertrophy. Int J Cardiovasc Imaging. 2008 Mar;24(3):261-7. doi: 10.1007/s10554-007-9265-1. Epub 2007 Sep 6.</citation>
    <PMID>17846918</PMID>
  </reference>
  <reference>
    <citation>Leung LC, Ng DK, Lau MW, Chan CH, Kwok KL, Chow PY, Cheung JM. Twenty-four-hour ambulatory BP in snoring children with obstructive sleep apnea syndrome. Chest. 2006 Oct;130(4):1009-17. doi: 10.1378/chest.130.4.1009.</citation>
    <PMID>17035432</PMID>
  </reference>
  <reference>
    <citation>Luna-Paredes C, Anton-Pacheco JL, Garcia Hernandez G, Martinez Gimeno A, Romance Garcia AI, Garcia Recuero II. Screening for symptoms of obstructive sleep apnea in children with severe craniofacial anomalies: assessment in a multidisciplinary unit. Int J Pediatr Otorhinolaryngol. 2012 Dec;76(12):1767-70. doi: 10.1016/j.ijporl.2012.08.020. Epub 2012 Sep 11.</citation>
    <PMID>22980525</PMID>
  </reference>
  <reference>
    <citation>Plomp RG, Bredero-Boelhouwer HH, Joosten KF, Wolvius EB, Hoeve HL, Poublon RM, Mathijssen IM. Obstructive sleep apnoea in Treacher Collins syndrome: prevalence, severity and cause. Int J Oral Maxillofac Surg. 2012 Jun;41(6):696-701. doi: 10.1016/j.ijom.2012.01.018. Epub 2012 Apr 20.</citation>
    <PMID>22521672</PMID>
  </reference>
  <reference>
    <citation>Zandieh SO, Padwa BL, Katz ES. Adenotonsillectomy for obstructive sleep apnea in children with syndromic craniosynostosis. Plast Reconstr Surg. 2013 Apr;131(4):847-852. doi: 10.1097/PRS.0b013e3182818f3a.</citation>
    <PMID>23542256</PMID>
  </reference>
  <reference>
    <citation>Chervin RD, Hedger K, Dillon JE, Pituch KJ. Pediatric sleep questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems. Sleep Med. 2000 Feb 1;1(1):21-32. doi: 10.1016/s1389-9457(99)00009-x.</citation>
    <PMID>10733617</PMID>
  </reference>
  <reference>
    <citation>Franco RA Jr, Rosenfeld RM, Rao M. First place--resident clinical science award 1999. Quality of life for children with obstructive sleep apnea. Otolaryngol Head Neck Surg. 2000 Jul;123(1 Pt 1):9-16. doi: 10.1067/mhn.2000.105254.</citation>
    <PMID>10889473</PMID>
  </reference>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>April 14, 2020</last_update_submitted>
  <last_update_submitted_qc>April 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Glenn Green</investigator_full_name>
    <investigator_title>Sponsor-Investigator</investigator_title>
  </responsible_party>
  <keyword>Obstructive Sleep Apnea</keyword>
  <keyword>Craniofacial Abnormalities</keyword>
  <keyword>Pediatrics</keyword>
  <keyword>Computer-Aided Design</keyword>
  <keyword>Continuous Positive Airway Pressure</keyword>
  <keyword>Three-Dimensional Printing</keyword>
  <keyword>Additive Manufacturing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Craniofacial Abnormalities</mesh_term>
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
    <mesh_term>Congenital Abnormalities</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02261857
org study id: HUM00078727
nct id: NCT02261857
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to determine whether patient-specific computer-aided design
      (CAD) and three-dimensional (3D) printing can be utilized to produce personalized, effective
      continuous positive airway pressure (CPAP) masks for children with severe obstructive sleep
      apnea (OSA) and craniofacial anomalies who encounter significant difficulty using CPAP
      because of poorly fitting masks despite exhausting available commercial mask options.
Obstructive sleep apnea (OSA) is a common problem in the general pediatric population,
      generally cited as between 1-5%, with morbidity ranging from daytime behavioral problems and
      inattention to cardiopulmonary effects including hypertension and ventricular hypertrophy.
      OSA is dramatically more prevalent among children with certain craniofacial anomalies and
      syndromes (e.g. Pierre-Robin, Treacher Collins, etc.), generally because of small, short
      jaws, midface hypoplasia, and/or disproportionally large tongues . While tonsillectomy and
      adenoidectomy is considered first line therapy for OSA in the general pediatric population,
      children with OSA due to craniofacial anomalies frequently require more aggressive
      intervention to improve their breathing at night, which often includes continuous positive
      airway pressure ventilation (CPAP). Most children who require CPAP therapy are able to find a
      mask that will adequately seal while providing acceptable comfort, however a small percentage
      of children encounter significant difficulty finding a functional CPAP interface, most often
      because of dysmorphic facial features. This can prove a significant barrier to effective CPAP
      therapy and lead to frustration on the part of patients' caregivers and providers, as well as
      the associated morbidity of untreated severe OSA. The purpose of this feasibility study is to
      investigate the use of patient-specific computational design and three-dimensional (3D)
      printing to produce personalized CPAP masks for children intolerant of standard CPAP masks
      due to poor fit secondary to craniofacial anomalies who encounter significant difficulty
      using CPAP because of poorly fitting masks despite exhausting available commercial mask
      options.

      Study Design

      This will be a prospective case study examining the feasibility of using patient-specific CAD
      and 3D printing technology to produce personalized CPAP masks for children intolerant of
      commercially available masks due to poor fit. Patients will be recruited from the pediatric
      otolaryngology, pediatric oral maxillofacial surgery, and pediatric sleep clinics at the
      University of Michigan Medical Center, with a target cohort of five.

      Only patients of study team members will be included in the study, and no recruitment will
      take place outside the clinics of participating study team members. We anticipate the study
      period to last 3 years, though it may terminate sooner if recruitment targets are reached
      expeditiously.

      After recruitment and consent of a potential study subject, each subject will undergo an
      initial mask-design evaluation with members of the research team. At this initial visit, the
      following will be performed:

        1. A head & neck physical exam, which a focus on characteristics important for treatment of
           OSA (e.g. jaw size and position, tongue size and position, characteristics of palate,
           presence or absence of cleft, external nasal deformity, external or internal nasal
           valvular collapse)

        2. Review of patient's photographs

        3. Generation of a topographic model of the patient's facial anatomy utilizing the 3dMDface
           system (specifics below) which will be export as a Stereolithography (.STL) file.

      The patient's facial .STL file will then be imported into a computer-aided design (CAD)
      modeling program (MimicsTM or MagicsTM, Materialise, Belgium). Contact points along the
      topographic model are drawn out and utilized for modeling of the custom mask. The custom mask
      model is then exported in .STL format for import into the 3D printer for fabrication using a
      fused-deposition modeling (FDM) method (Object Pro, Stratasys, Israel).

      Once the mask has been fabricated, patients will undergo a mask-fit evaluation. If a mask
      appears to fit well, the patient will use it at home with home CPAP for one month of
      consistent use. They will then return for debriefing and re-evaluation, with subsequent
      iterations of mask design as needed. If the mask functions for the patient better than any
      other alternatives, the patient will be allowed to continue to use the mask for up to one
      year, with ongoing surveillance by the research team, assessing for mask durability and
      ongoing usage/compliance.

      Data collection will include:

        -  Objective data regarding the nature of each patient's obstructive sleep apnea and CPAP
           pressure requirements sleep-disordered breathing from the most recent available
           polysomnograms (sleep study, abbreviated PSG)

        -  Information regarding all prior CPAP masks attempted

        -  One month compliance data downloads from CPAP machines - with both the prior "best
           alternative" if usable, and with the customized mask, including percentage of days used,
           average hours usage, residual apnea-hypopnea index (AHI) and time spent in large leak
           per night.

        -  Standardized interview with patients and their parents regarding other masks used and
           experience with the customized mask(s).

        -  Descriptive anatomic information regarding facial anomalies contributing to poor mask
           fit, obtained from physical exam, photographs, and imaging studies.

        -  Validated quality of life measures taken before and at completion of trial period with
           customized CPAP mask, including the Pediatric Sleep Questionnaire (PSQ) and the OSA-18 ,
           to assess the impact of successful CPAP use for our patients.

      Analysis will involve basic descriptive statistics to describe both the objective outcomes
      (e.g. compliance data from CPAP machines) and quality of life measures (PSQ and OSA-18
      surveys) as well as information on individual experiences collected during interviews.

      Additional Data on 3D Photography System

      Patient facial modeling information will be obtained utilizing a 3dMDface system (3dMD,
      Atlanta, GA). The 3dMD system is a three-dimensional photography system which generates a
      three-dimensional model of the patient's face utilizing multiple convergent cameras (see
      Figure 1 below). The three-dimensional model is generated utilizing hybrid
      stereophotogrammetry, with software algorithms using both projected random patterns and
      texture of the skin (pores, freckles, etc.) to stereo-triangulate and generate a 3D surface
      image. The 3D model of the patient's face is created within the 3dMDvultus software system,
      which can then export the model in .STL format. No patient identifying information is stored
      within the .STL file.

      All 3D photography sessions with study subjects will be performed or supervised by one of the
      members of the study team. There will be no cost associated with using the 3dMDface system.
      Utilizing 3D photography allows us to obtain the most time-accurate topographic information
      of the patient's face while avoiding the cost and risk associated with conventional CT or MRI
      imaging.

      Data Included in Registry:

        -  Pre- and post- intervention OSA-18 and PSQ questionnaire aggregates. Data to be recorded
           includes: sum score and mean score for each questionnaire.

        -  Pre-intervention AHI and oxygen saturation (SpO2) nadir based on most recent sleep PSG.

        -  Pre-intervention CPAP requirements based on most recent CPAP titration PSG.

        -  Pre-intervention compliance data downloads from subject's CPAP machines from prior 1
           month's use. Data to be recorded includes: percentage of days used, average hours usage,
           residual apnea-hypopnea index (AHI), size of leak in liters per minute, and time spent
           in large leak per night.

        -  Post-intervention compliance data downloads from subject's CPAP machines from prior 1
           month's use. Data to be recorded includes: percentage of days used, average hours usage,
           residual apnea-hypopnea index (AHI), size of leak in liters per minute, and time spent
           in large leak per night.

      Data Registry QA:

      • Physical and electronic PDF versions of each data registry primary source (questionnaires,
      polysomnograms, and CPAP compliance reports) will be kept for the 5 years past the duration
      of the study. Data uploaded to the patient registry will be verified with the institutional
      IRB.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in CPAP Compliance at 1 month
time frame: 1 month
description: Subject CPAP usage data will be downloaded from their CPAP machine before beginning the use to personalized mask (baseline) and after 1 month of consistent use of the personalized mask (1 month post-intervention). Average hours usage will be recorded and compared between baseline CPAP usage data and 1 month post-intervention CPAP usage data to assess efficacy of the personalized mask compared to the best prior alternative. Outcome will be measured as a numerical value in hours per night.
measure: Change in CPAP Leak Rate at 1 month
time frame: 1 month
description: Subject CPAP usage data will be downloaded from their CPAP machine before beginning the use to personalized mask (baseline) and after 1 month of consistent use of the personalized mask (1 month post-intervention). Leak in liters per minute will be recorded and compared between baseline CPAP usage data and 1 month post-intervention CPAP usage data to assess efficacy of the personalized mask compared to the best prior alternative. Outcome will be measured as a numerical value in liters per minute.
measure: Change in residual AHI on CPAP at 1 month
time frame: 1 month
description: Subject CPAP usage data will be downloaded from their CPAP machine before beginning the use to personalized mask (baseline) and after 1 month of consistent use of the personalized mask (1 month post-intervention). Residual apnea-hypopnea index (AHI) will be recorded and compared between baseline CPAP usage data and 1 month post-intervention CPAP usage data to assess efficacy of the personalized mask compared to the best prior alternative. Outcome will be measured as a numerical value denoting AHI.
measure: Change in time spent in large leak on CPAP at 1 month
time frame: 1 month
description: Subject CPAP usage data will be downloaded from their CPAP machine before beginning the use to personalized mask (baseline) and after 1 month of consistent use of the personalized mask (1 month post-intervention). Percentage (%) time spent in large leak per night will be recorded and compared between baseline CPAP usage data and 1 month post-intervention CPAP usage data to assess efficacy of the personalized mask compared to the best prior alternative. Outcome will be measured as a numerical percentage as a percentage of total time spent in large leak per night over total time using CPAP per night.
measure: Change in Quality of Life via OSA-18 questionnaire
time frame: 1 month
description: Subject's parents or legal guardians will complete OSA-18 questionnaire (validated OSA quality of of life questionnaires) pre-intervention (baseline) and at 1-month post-intervention. These will be compared to assess effect on quality of life of the interventional device. Outcome will be measured as a numerical value as sum of all question value responses.
measure: Safety outcomes: Comfort at baseline
time frame: Baseline
description: Subjects will be assessed clinically when first wearing the interventional device to ensure there are no issues with device fit, comfort, or undue forces on the face. Outcome will be measured as a binary numerical value with 0 denoting no issues with comfort and 1 denoting issues with comfort.
measure: Safety outcomes: Comfort at 1 month
time frame: 1 month
description: Subjects will be assessed clinically after using the personalized mask consistently for 1 month at home to ensure there are no issues with device fit, comfort or undue forces on the face. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with comfort and 1 denoting issues with comfort.
measure: Safety outcomes: Skin reaction at 1 month
time frame: 1 month
description: Subjects will be assessed clinically after using the personalized mask consistently for 1 month at home to ensure there are no issues with skin reaction or breakdown on the face. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with skin reaction and 1 denoting issues with skin reaction.
measure: Change in Quality of Life via PSQ questionnaire
time frame: 1 month
description: Subject's parents or legal guardians will complete PSQ questionnaire (validated OSA quality of of life questionnaires) pre-intervention (baseline) and at 1-month post-intervention. These will be compared to assess effect on quality of life of the interventional device. Outcome will be measured as a numerical value as sum of all question value responses.
measure: Safety outcomes: durability at 1 month
time frame: 1 month
description: Subjects will be assessed clinically after using the personalized mask consistently for 1 month at home to ensure there are no issues with excessive wear or tear of the personalized mask. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with durability and 1 denoting issues with durability.
measure: Safety outcomes: Skin reaction at 12 months
time frame: 12 months
description: Subjects will be assessed clinically after using the personalized mask consistently for 12 months at home to ensure there are no issues with skin reaction or breakdown on the face. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with skin reaction and 1 denoting issues with skin reaction.
measure: Safety outcomes: Durability at 12 months
time frame: 12 months
description: Subjects will be assessed clinically after using the personalized mask consistently for 12 months at home to ensure there are no issues with excessive wear or tear of the personalized mask. Subject's parents or legal guardians are instructed to contact the study team for earlier follow-up at anytime if any concerns about device fit or use occur. Outcome will be measured as a binary numerical value with 0 denoting no issues with durability and 1 denoting issues with durability.
arm group label: Intervention Arm
arm group type: Experimental
description: Intervention: Subjects will undergo assessment and a personalized CPAP mask device will be manufactured using patient-specific computer-aided design and 3D printing. The subject will use the personalized CPAP mask for 1 month of consistent use and post-intervention data will be collected for compare to historical control (see other arm)
arm group label: Historical Control Arm
arm group type: No Intervention
description: Pre-interventional baseline data on subject OSA, CPAP compliance, and quality of life (QoL) measures will be collected to serve as historical controls.
intervention type: Device
intervention name: Personalized continuous positive airway pressure (CPAP) mask
description: Personalized CPAP mask manufactured for study subjects using a combination of patient-specific computer-aided design and three-dimensional printing
arm group label: Intervention Arm
criteria: 
gender: All
minimum age: 1 Year
maximum age: 18 Years
healthy volunteers: No
last name: Glenn E Green, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
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PMID: 22926176
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PMID: 11742924
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PMID: 12016102
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PMID: 17846918
citation: Leung LC, Ng DK, Lau MW, Chan CH, Kwok KL, Chow PY, Cheung JM. Twenty-four-hour ambulatory BP in snoring children with obstructive sleep apnea syndrome. Chest. 2006 Oct;130(4):1009-17. doi: 10.1378/chest.130.4.1009.
PMID: 17035432
citation: Luna-Paredes C, Anton-Pacheco JL, Garcia Hernandez G, Martinez Gimeno A, Romance Garcia AI, Garcia Recuero II. Screening for symptoms of obstructive sleep apnea in children with severe craniofacial anomalies: assessment in a multidisciplinary unit. Int J Pediatr Otorhinolaryngol. 2012 Dec;76(12):1767-70. doi: 10.1016/j.ijporl.2012.08.020. Epub 2012 Sep 11.
PMID: 22980525
citation: Plomp RG, Bredero-Boelhouwer HH, Joosten KF, Wolvius EB, Hoeve HL, Poublon RM, Mathijssen IM. Obstructive sleep apnoea in Treacher Collins syndrome: prevalence, severity and cause. Int J Oral Maxillofac Surg. 2012 Jun;41(6):696-701. doi: 10.1016/j.ijom.2012.01.018. Epub 2012 Apr 20.
PMID: 22521672
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PMID: 23542256
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PMID: 10889473
responsible party type: Sponsor-Investigator
investigator affiliation: University of Michigan
investigator full name: Glenn Green
investigator title: Sponsor-Investigator
mesh term: Craniofacial Abnormalities
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Congenital Abnormalities