<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/NCT03033901</url>
  </required_header>
  <id_info>
    <org_study_id>CER-1511-33005</org_study_id>
    <nct_id>NCT03033901</nct_id>
  </id_info>
  <brief_title>Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome</brief_title>
  <acronym>C-SAS</acronym>
  <official_title>Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>James A. Haley Veterans Administration Hospital</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Patient-Centered Outcomes Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Craig Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Moss Rehabilitation Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Baylor Institute for Rehabilitation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of South Florida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Palo Alto Veterans Institute for Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>North Florida Foundation for Research and Education</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>James A. Haley Veterans Administration Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Sleep disorders, including sleep apnea, are common after traumatic brain injury&#xD;
      and affect recovery and negatively influence participation in rehabilitation. Sleep apnea is&#xD;
      a breathing problem while persons sleep and causes further brain damage and problems with&#xD;
      thinking, daily functioning, and overall health. Earlier diagnosis and treatment is important&#xD;
      for traumatic brain injury (TBI) survivors to maximize the recovery process. There is little&#xD;
      information that guides TBI doctors on how to identify sleep apnea during inpatient TBI&#xD;
      rehabilitation, a phase in which people experience the potential for a rapid pace of&#xD;
      improvement. The Agency for Healthcare Research has highlighted gaps in best methods for&#xD;
      identifying sleep apnea and separately in helping consumers with TBI rehabilitation choices.&#xD;
      Partnering with survivors, caregivers, and administrators, investigators developed this study&#xD;
      to compare sleep apnea screening and diagnostic tools in TBI rehabilitation settings. This&#xD;
      information will provide clinicians, providers, and patients with the best information for&#xD;
      early identification of sleep apnea to remove negative influence on the pace of recovery in&#xD;
      early phases after TBI.&#xD;
&#xD;
      The Goal: Investigators will compare existing screening (Aim 1) and diagnostic tools (Aim 2)&#xD;
      in TBI patients undergoing inpatient rehabilitation. For the second aim, investigators will&#xD;
      determine if a more accessible diagnostic test is sufficient to diagnose sleep apnea compared&#xD;
      to the traditional method used which is less accessible to consumers. If the more accessible&#xD;
      test is good enough, this will increase recognition of this problem and increase patient&#xD;
      access to earlier sleep apnea treatment.&#xD;
&#xD;
      Stakeholders and Products. TBI survivors, caregivers, researchers, and policymakers working&#xD;
      together on this study helped develop the study questions. Idea exchanges included ways to&#xD;
      reach clinicians and TBI survivors/caregivers via existing educational programming and online&#xD;
      tools for consumers such as fact sheets and patient/caregiver-focused videos. Other&#xD;
      traditional methods will include targeting professional magazines, conferences, and research&#xD;
      journals that reach professionals working with TBI survivors and their families at the time&#xD;
      of admission to rehabilitation and during the recovery process. This study will occur at&#xD;
      rehabilitation hospitals around the country who enroll TBI survivors into a lifetime study&#xD;
      called the TBI Model System funded by the Department of Health and Human Services and&#xD;
      Veterans Affairs (VA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background and Significance:&#xD;
&#xD;
      Meta-analyses of TBI studies found prevalence of obstructive sleep apnea (OSA) was 12 times&#xD;
      higher than community-based studies. Yet, sleep apnea in those with TBI is largely&#xD;
      undiagnosed. Given that sleep is critical for neural repair and disordered sleep may play a&#xD;
      role in slowing functional recovery and prolonging rehabilitation, early detection of sleep&#xD;
      apnea is critical (Stakeholder Input). Minimal guidance exists informing TBI and sleep&#xD;
      medicine physicians regarding assessment of sleep disorders in the acute rehabilitation&#xD;
      setting. The Agency for Healthcare Research and Quality's (AHRQ) Comparative Effectiveness&#xD;
      Review highlighted insufficient comparative effectiveness evidence for diagnostic and&#xD;
      screening tools. This study proposes to leverage the existing TBI Model System research&#xD;
      consortium (TBIMS), funded by the Departments of Health and Human Services and Veterans&#xD;
      Affairs, to improve early detection of sleep apnea in patients with TBI undergoing inpatient&#xD;
      rehabilitation at six study sites. Study aims are focused around components of phased testing&#xD;
      for sleep apnea. Findings will inform clinician's decisions for screening and diagnostic&#xD;
      tests to facilitate earlier recognition of sleep apnea (outcome) and subsequently prescribe&#xD;
      appropriate treatments.&#xD;
&#xD;
      Study Aims:&#xD;
&#xD;
      Aim I: (Screening) For individuals with TBI, determine comparative effectiveness of 2&#xD;
      American Academy of Sleep Medicine (AASM) endorsed screening tools (STOPBang Questionnaire&#xD;
      [STOPBang] vs. Actigraphy [ACG]) to identify those at high risk of sleep apnea as diagnosed&#xD;
      through Level 1 polysomnography (PSG). Long-term Objectives: To inform clinician's choices&#xD;
      for screening measures to determine presence of sleep apnea.&#xD;
&#xD;
      Exploratory Aim:&#xD;
&#xD;
      Evaluate alternative screening tools (Berlin Questionnaire, Multivariate Apnea Prediction&#xD;
      Index [MAPI]) to Level 1 PSG in Aim 1.&#xD;
&#xD;
      Aim II: (Diagnosis) This study will determine the diagnostic accuracy (non-inferiority) of&#xD;
      Level 3 PSG in determining presence of sleep apnea in patients with acute TBI patients in the&#xD;
      rehabilitation setting. Level 1 PSG will be used as the criterion standard. Long-term&#xD;
      Objectives: To inform clinician's choices of diagnostic tests to determine presence of sleep&#xD;
      apnea and prescribe appropriate treatments. If Level 3 portable PSG is equivalent to the less&#xD;
      accessible Level 1 PSG, this will increase consumer accessibility.&#xD;
&#xD;
      Study Design:&#xD;
&#xD;
      This is a 3-year, multi-center prospective observational cohort study.&#xD;
&#xD;
      Intervention and Comparators:&#xD;
&#xD;
      In Aim I, the screening tools STOPBang and ACG will be compared against one another to&#xD;
      determine their sensitivity and specificity in identifying patients with TBI at risk for&#xD;
      sleep apnea. In Aim II, the non-inferiority of Level 3 PSG in determining presence and&#xD;
      severity of sleep apnea in patients with moderate to severe TBI will be compared to Level 1&#xD;
      PSG.&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
      Consecutive participants to neurorehabilitation at an existing National Institute on&#xD;
      Disability, Independent Living, and Rehabilitation Research (NIDILRR) or VA funded TBIMS&#xD;
      Center will make up the study population. Patients will be age 16 and older (18 or older at&#xD;
      VA sites), with moderate to severe TBI, admitted for rehabilitation in a U.S. TBIMS inpatient&#xD;
      rehabilitation facility, and sleeping &gt; 2 hours/night suggesting habitual sleep duration.&#xD;
      Based on historical data from the six study sites participating in this study, investigators&#xD;
      in this study conservatively estimated that 70% of patients admitted for inpatient TBI&#xD;
      rehabilitation would consent into this study (N=20/month), resulting in a 13-month enrollment&#xD;
      estimate of 259 patients. Power analyses of each study aim suggest that a sample size of 237&#xD;
      is the largest sample size needed for sufficient power. The sites participating in this study&#xD;
      aim to collectively enroll 259 patients to account for possible further attrition. Based on&#xD;
      TBIMS data acquired over the past 25-years, 44% of the sample is female, 64% are categorized&#xD;
      as Non-White, median age is 38 years, with predominantly moderate to severe TBI.&#xD;
&#xD;
      Primary outcomes consist of:&#xD;
&#xD;
      1) Positive predictive power of screening tools: STOPBang and ACG, 2) Equivalency in&#xD;
      detection of sleep apnea via Level 1 and Level 3 PSG, with diagnosis of sleep apnea based on&#xD;
      overall apnea-hypopnea index (AHI) &gt; 5.&#xD;
&#xD;
      Analytic Methods:&#xD;
&#xD;
      Aim 1: Investigators expect that STOPBang values &gt; 5 and abnormal ACG total sleep time (&lt; 5&#xD;
      hours with desaturation) will produce sufficiently high SEs with reasonable tradeoff in SP&#xD;
      (noting that SE and SP are inversely related). Similarly, for Level 1 PSG, a diagnosis of&#xD;
      sleep apnea will be made if AHI ≥ 5. Cross-tabulations of STOPBang and ACG screening for high&#xD;
      risk of sleep apnea (positive/negative) versus Level 1 PSG diagnosis (positive/negative) will&#xD;
      be constructed and estimates of diagnostic accuracy (i.e., sensitivity, specificity, positive&#xD;
      and negative predictive values, and diagnostic accuracy) will be estimated along with 95%&#xD;
      confidence intervals. To address hypothesis 1.1, two-sided McNemar's tests will be used to&#xD;
      compare the paired SEs and paired SPs between STOPBang and ACG assuming a significance level&#xD;
      of α = 0.05.&#xD;
&#xD;
      Aim 2: The sensitivity (SE) and specificity (SP) of Level 3 PSG (compared to Level 1 PSG, the&#xD;
      reference gold standard) will each be estimated and compared to fixed hypothesized rates of&#xD;
      SE and SP of 90% and 60%, respectively, considered sufficiently large enough. Level 1 PSG&#xD;
      (reference) diagnosis of sleep apnea will be made based on AHI ≥ 5. Level 3 PSG (test)&#xD;
      diagnosis will be made based AHI ≥ 5. A cross-tabulation of Level 3 PSG (positive/negative)&#xD;
      versus Level 1 PSG (positive/negative) will be constructed and standard measures of&#xD;
      diagnostic accuracy will be estimated along with 95% confidence intervals (i.e., sensitivity,&#xD;
      specificity, positive and negative predictive values, and diagnostic accuracy).To test for&#xD;
      non-inferiority of the SE to 90% and the SP to 60%, a non-inferiority threshold of 0.1 is&#xD;
      assumed. If the lower bound on the 95% confidence interval for SE is strictly above 80% and&#xD;
      the lower bound on the confidence interval for SP is strictly above 50% then non-inferiority&#xD;
      of Level 3 PSG (compared to Level 3 PSG) can be established.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2017</start_date>
  <completion_date type="Actual">February 1, 2020</completion_date>
  <primary_completion_date type="Actual">February 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Apnea-Hypopnea Index (AHI)</measure>
    <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-traumatic brain injury (TBI) in civilian settings and 132 days in Veterans Affairs (VA) settings.</time_frame>
    <description>A diagnosis of sleep apnea will be determined by overall apnea-hypopnea index (AHI) greater or equal to 5 and greater than or equal to 15 denoting different severity levels of disease.</description>
  </primary_outcome>
  <other_outcome>
    <measure>STOPBang Sleep Apnea Risk</measure>
    <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.</time_frame>
    <description>Sleep apnea screening measure. Risk based on responses to 8 items (2,low risk; 3-4, intermediate risk; &gt;5, high risk).</description>
  </other_outcome>
  <other_outcome>
    <measure>Berlin Sleep Apnea Risk</measure>
    <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.</time_frame>
    <description>Sleep apnea screening measure with 10-items. Risk stratification is based on number of items: no risk (no items endorsed), low (endorsement of 1 item) or high risk (endorsement of 2 or more items).</description>
  </other_outcome>
  <other_outcome>
    <measure>Actigraphy</measure>
    <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.</time_frame>
    <description>Philips brand Actiwatch Spectrum used to measure total sleep time</description>
  </other_outcome>
  <other_outcome>
    <measure>Multivariate Apnea Prediction Index (MAPI)</measure>
    <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.</time_frame>
    <description>The questionnaire consists of 3 breathing-related questions and information on demographics (sex, weight, height, age), from which a probability of having sleep apnea (0%-100%) can be calculated. The test-retest reliability of the breathing questions is 0.92 and has a good internal consistency with Cronbach a of 0.85-0.93. A MAPI score of 0.50 (ie, calculated 0% likelihood of having clinically significant sleep apnea with a Respiratory Distress Index&gt;10) has a 0.88 sensitivity and 0.55 specificity.</description>
  </other_outcome>
  <enrollment type="Actual">345</enrollment>
  <condition>Apnea, Sleep</condition>
  <condition>Brain Injury, Traumatic</condition>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Polysomnography - Level 1 and Level 3</intervention_name>
    <description>Participants will undergo simultaneous administration of Level 1 and 3 polysomnography on the rehabilitation unit with study funded sleep technologist present to meet Level 1 standards.</description>
    <other_name>Philips Respironics Alice 6 Lab Diagnostic System</other_name>
    <other_name>Nox T3</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Actigraphy monitoring</intervention_name>
    <description>Participants will undergo actigraphy monitoring to assess habitual sleep duration to determine readiness for polysomnography and examine trajectory and duration of sleep.</description>
    <other_name>Philips Respironics Airway (AW) Spectrum Plus Actiwatch</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sleep Apnea Screening</intervention_name>
    <description>Participants and their family member or proxy, and clinical staff will be asked to answer questions in order to complete the three standardized sleep apnea screening measures.</description>
    <other_name>Berlin Questionnaire</other_name>
    <other_name>STOPBang Questionnaire</other_name>
    <other_name>Multivariate Apnea Prediction Index</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will be TBI patients admitted to inpatient rehabilitation at an&#xD;
        existing NIDILRR or VA funded TBI Model System Center who meet study inclusion and&#xD;
        exclusion criteria.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Meet case definition for TBI:&#xD;
&#xD;
             (A). VA (for James A. Haley Veterans' Hospital): i. Persons fitting the definition of&#xD;
             traumatic brain injury (TBI), defined as a traumatically induced structural brain&#xD;
             injury, brain trauma, or damage to brain tissue, and/or physiological disruption of&#xD;
             brain function as a result of an external mechanical force (also including&#xD;
             acceleration/deceleration movement without direct external trauma to the head, a&#xD;
             foreign body penetrating the brain, forces generated from events such as a blast or&#xD;
             explosion, or other force) as evidenced by self-reported or medically documented&#xD;
             (physical examination or mental status examination) new onset or worsening of at least&#xD;
             one of the following clinical signs immediately following the event: (a) a period of&#xD;
             loss of or a decreased level of consciousness; (b) alteration in mental state at the&#xD;
             time of the injury (confusion, disorientation, slowed thinking); (c) loss of memory&#xD;
             for events immediately before or after the injury; (d) posttraumatic amnesia (PTA);&#xD;
             (d)neurological deficits (weakness, imbalance, change in vision, praxis,&#xD;
             paresis/plegia, sensory loss, aphasia, etc.) that may or may not be transient; or (e)&#xD;
             intracranial lesion. ii. Age 18 or older at the time of index TBI. iii. Admitted to&#xD;
             one of the five designated VA Polytrauma Rehabilitation Centers (PRCs) for&#xD;
             comprehensive rehabilitation with the presenting diagnoses of TBI. Comprehensive&#xD;
             rehabilitation must occur in the PRC and meet the following criteria: (a) Medical and&#xD;
             rehabilitation care are supervised on a regular basis by a physician affiliated with&#xD;
             the PRC; (b) 24-hour nursing care is provided to the patient; (c) Physical Therapy&#xD;
             (PT), Occupational Therapy (OT), Speech, Rehabilitation Psychology, Neuropsychology,&#xD;
             and/or family support/education are provided in an integrated team approach with the&#xD;
             expectation of further gain; (d) Operates in a manner consistent with Commission on&#xD;
             Accreditation of Rehabilitation Facilities (CARF) standards for brain injury inpatient&#xD;
             rehabilitation and/or Medicare requirements for inpatient rehabilitation.&#xD;
&#xD;
             OR&#xD;
&#xD;
             (B). Civilian (for civilian sites): Damage to brain tissue caused by an external&#xD;
             mechanical force, alteration of consciousness &gt; 24 hours, or loss of consciousness &gt;30&#xD;
             minutes, or Glasgow Coma Scale (GCS) score in the Emergency Department of3-12, or&#xD;
             intracranial abnormalities on imaging regardless of GCS;&#xD;
&#xD;
             AND&#xD;
&#xD;
          2. admission to an inpatient brain injury rehabilitation program;&#xD;
&#xD;
          3. minimum age 16 years at civilian sites and 18 years at the VA site;&#xD;
&#xD;
          4. Understands and provides informed consent to participate (or, if unable, healthcare&#xD;
             proxy / legal guardian understands and provides informed consent for the patient);&#xD;
&#xD;
          5. sleep duration &gt; 2 hours/night.&#xD;
&#xD;
        Although not specifically targeted, pregnant women and people with intellectual&#xD;
        developmental disorders or prior psychiatric histories meeting the above&#xD;
        inclusion/exclusion criteria can be enrolled in this study. Individuals with known history&#xD;
        of sleep apnea will be eligible for the study and apnea status will be reconfirmed with new&#xD;
        diagnostic study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. persons less than 16 years old at civilian sites and less than 18 years old at VA site&#xD;
             will not be included;&#xD;
&#xD;
          2. pre-injury diagnosis of narcolepsy or persistent daytime somnolence as documented in&#xD;
             patient's medical record and/or family report; and/or&#xD;
&#xD;
          3. tracheostomy placed and decannulation or overnight capping of the tracheostomy not&#xD;
             feasible during rehabilitation hospitalization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Risa Richardson, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>James A. Haley Veterans' Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Craig Hospital</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James A. Haley Veterans' Hospital</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert Einstein Healthcare Network/Moss Rehabilitation Hospital</name>
      <address>
        <city>Elkins Park</city>
        <state>Pennsylvania</state>
        <zip>19027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Institute for Rehabilitation</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.tbindsc.org/</url>
    <description>NIDILRR-funded TBI Model System website</description>
  </link>
  <reference>
    <citation>Holcomb EM, Schwartz DJ, McCarthy M, Thomas B, Barnett SD, Nakase-Richardson R. Incidence, Characterization, and Predictors of Sleep Apnea in Consecutive Brain Injury Rehabilitation Admissions. J Head Trauma Rehabil. 2016 Mar-Apr;31(2):82-100. doi: 10.1097/HTR.0000000000000230.</citation>
    <PMID>26959663</PMID>
  </reference>
  <reference>
    <citation>Kamper JE, Garofano J, Schwartz DJ, Silva MA, Zeitzer J, Modarres M, Barnett SD, Nakase-Richardson R. Concordance of Actigraphy With Polysomnography in Traumatic Brain Injury Neurorehabilitation Admissions. J Head Trauma Rehabil. 2016 Mar-Apr;31(2):117-25. doi: 10.1097/HTR.0000000000000215.</citation>
    <PMID>26959665</PMID>
  </reference>
  <reference>
    <citation>Towns SJ, Zeitzer J, Kamper J, Holcomb E, Silva MA, Schwartz DJ, Nakase-Richardson R. Implementation of Actigraphy in Acute Traumatic Brain Injury (TBI) Neurorehabilitation Admissions: A Veterans Administration TBI Model Systems Feasibility Study. PM R. 2016 Nov;8(11):1046-1054. doi: 10.1016/j.pmrj.2016.04.005. Epub 2016 May 10.</citation>
    <PMID>27178377</PMID>
  </reference>
  <reference>
    <citation>Nakase-Richardson R. Improving the Significance and Direction of Sleep Management in Traumatic Brain Injury. J Head Trauma Rehabil. 2016 Mar-Apr;31(2):79-81. doi: 10.1097/HTR.0000000000000235. No abstract available.</citation>
    <PMID>26959662</PMID>
  </reference>
  <reference>
    <citation>Holcomb EM, Towns S, Kamper JE, Barnett SD, Sherer M, Evans C, Nakase-Richardson R. The Relationship Between Sleep-Wake Cycle Disturbance and Trajectory of Cognitive Recovery During Acute Traumatic Brain Injury. J Head Trauma Rehabil. 2016 Mar-Apr;31(2):108-16. doi: 10.1097/HTR.0000000000000206.</citation>
    <PMID>26709584</PMID>
  </reference>
  <reference>
    <citation>Nakase-Richardson R, Sherer M, Barnett SD, Yablon SA, Evans CC, Kretzmer T, Schwartz DJ, Modarres M. Prospective evaluation of the nature, course, and impact of acute sleep abnormality after traumatic brain injury. Arch Phys Med Rehabil. 2013 May;94(5):875-82. doi: 10.1016/j.apmr.2013.01.001. Epub 2013 Jan 4.</citation>
    <PMID>23296143</PMID>
  </reference>
  <reference>
    <citation>Silva MA, Nakase-Richardson R, Sherer M, Barnett SD, Evans CC, Yablon SA. Posttraumatic confusion predicts patient cooperation during traumatic brain injury rehabilitation. Am J Phys Med Rehabil. 2012 Oct;91(10):890-3. doi: 10.1097/PHM.0b013e31825a1648.</citation>
    <PMID>22660372</PMID>
  </reference>
  <reference>
    <citation>Nakase-Thompson R, Sherer M, Yablon SA, Nick TG, Trzepacz PT. Acute confusion following traumatic brain injury. Brain Inj. 2004 Feb;18(2):131-42. doi: 10.1080/0269905031000149542.</citation>
    <PMID>14660226</PMID>
  </reference>
  <reference>
    <citation>Nakase-Richardson R, Dahdah MN, Almeida E, Ricketti P, Silva MA, Calero K, Magalang U, Schwartz DJ. Concordance between current American Academy of Sleep Medicine and Centers for Medicare and Medicare scoring criteria for obstructive sleep apnea in hospitalized persons with traumatic brain injury: a VA TBI Model System study. J Clin Sleep Med. 2020 Jun 15;16(6):879-888. doi: 10.5664/jcsm.8352.</citation>
    <PMID>32043962</PMID>
  </reference>
  <reference>
    <citation>Nakase-Richardson R, Schwartz DJ, Ketchum JM, Drasher-Phillips L, Dahdah MN, Monden KR, Bell K, Hoffman J, Whyte J, Bogner J, Calero K, Magalang U. Comparison of Diagnostic Sleep Studies in Hospitalized Neurorehabilitation Patients With Moderate to Severe Traumatic Brain Injury. Chest. 2020 Oct;158(4):1689-1700. doi: 10.1016/j.chest.2020.03.083. Epub 2020 May 6.</citation>
    <PMID>32387522</PMID>
  </reference>
  <reference>
    <citation>Nakase-Richardson R, Hoffman JM, Magalang U, Almeida E, Schwartz DJ, Drasher-Phillips L, Ketchum JM, Whyte J, Bogner J, Dismuke-Greer CE. Cost-Benefit Analysis From the Payor's Perspective for Screening and Diagnosing Obstructive Sleep Apnea During Inpatient Rehabilitation for Moderate to Severe TBI. Arch Phys Med Rehabil. 2020 Sep;101(9):1497-1508. doi: 10.1016/j.apmr.2020.03.020. Epub 2020 May 4. Erratum In: Arch Phys Med Rehabil. 2021 Mar;102(3):561.</citation>
    <PMID>32376325</PMID>
  </reference>
  <reference>
    <citation>Zeitzer JM, Hon F, Whyte J, Monden KR, Bogner J, Dahdah M, Wittine L, Bell KR, Nakase-Richardson R. Coherence Between Sleep Detection by Actigraphy and Polysomnography in a Multi-Center, Inpatient Cohort of Individuals with Traumatic Brain Injury. PM R. 2020 Dec;12(12):1205-1213. doi: 10.1002/pmrj.12353. Epub 2020 Mar 26.</citation>
    <PMID>32125095</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 18, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <results_first_submitted>July 14, 2021</results_first_submitted>
  <results_first_submitted_qc>March 28, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 29, 2023</results_first_posted>
  <last_update_submitted>March 28, 2023</last_update_submitted>
  <last_update_submitted_qc>March 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Veterans</keyword>
  <keyword>Comparative Effectiveness Research</keyword>
  <keyword>Diagnosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Final de-identified data sets underlying publications resulting from the proposed research will be available outside VA in electronic format, through email upon request, after results are published. Data sets will be available for collaborators and other investigators upon request prior to publication (expected time period: 120 days post request). The extent of the data will be de-identified aggregate data only.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data will be available upon request following publication of the primary aims. Data will be made available while the Institutional Review Board (IRB) protocol remains active.</ipd_time_frame>
    <ipd_access_criteria>Data requests will be reviewed by the Study PI and responded to within 120 days of request. Data requests will follow the TBI Model System External Request Standard Operating Procedure (SOP) which is available at www.tbindsc.org.</ipd_access_criteria>
    <ipd_url>http://www.tbindsc.org</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 26, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/01/NCT03033901/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 18, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/01/NCT03033901/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Single Group</title>
          <description>Potential participants were screened for eligibility. Upon meeting study eligibility requirements, they were asked to consent. Upon consenting, they were screened additional study requirements before undergoing polysomnography.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="345"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="248"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Ineligible for Polysomnography (PSG)</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Refused PSG</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Total Sleep Time &lt; 2 hours</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Missing Oximetry Data</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Hospitalized moderate to severe traumatic brain injury participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Single Group</title>
          <description>Potential participants were screened for eligibility. Upon meeting study eligibility requirements, they were asked to consent. Upon consenting, they were screened additional study requirements before undergoing polysomnography.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="248"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43.6" spread="17.9"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="203"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Participant could identify as more than one race/ethnicity and may be counted in more than one race/ethnicity category.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="184"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="248"/>
                  </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>A diagnosis of sleep apnea will be determined by overall apnea-hypopnea index (AHI) greater or equal to 5 and greater than or equal to 15 denoting different severity levels of disease.</description>
        <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-traumatic brain injury (TBI) in civilian settings and 132 days in Veterans Affairs (VA) settings.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Group</title>
            <description>Potential participants were screened for eligibility. Upon meeting study eligibility requirements, they were asked to consent. Upon consenting, they were screened additional study requirements before undergoing polysomnography.</description>
          </group>
        </group_list>
        <measure>
          <title>Apnea-Hypopnea Index (AHI)</title>
          <description>A diagnosis of sleep apnea will be determined by overall apnea-hypopnea index (AHI) greater or equal to 5 and greater than or equal to 15 denoting different severity levels of disease.</description>
          <units>times per hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.4" spread="5.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>STOPBang Sleep Apnea Risk</title>
        <description>Sleep apnea screening measure. Risk based on responses to 8 items (2,low risk; 3-4, intermediate risk; &gt;5, high risk).</description>
        <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Group</title>
            <description>Potential participants were screened for eligibility. Upon meeting study eligibility requirements, they were asked to consent. Upon consenting, they were screened additional study requirements before undergoing polysomnography.</description>
          </group>
        </group_list>
        <measure>
          <title>STOPBang Sleep Apnea Risk</title>
          <description>Sleep apnea screening measure. Risk based on responses to 8 items (2,low risk; 3-4, intermediate risk; &gt;5, high risk).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.56" spread="1.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Berlin Sleep Apnea Risk</title>
        <description>Sleep apnea screening measure with 10-items. Risk stratification is based on number of items: no risk (no items endorsed), low (endorsement of 1 item) or high risk (endorsement of 2 or more items).</description>
        <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Group</title>
            <description>Potential participants were screened for eligibility. Upon meeting study eligibility requirements, they were asked to consent. Upon consenting, they were screened additional study requirements before undergoing polysomnography.</description>
          </group>
        </group_list>
        <measure>
          <title>Berlin Sleep Apnea Risk</title>
          <description>Sleep apnea screening measure with 10-items. Risk stratification is based on number of items: no risk (no items endorsed), low (endorsement of 1 item) or high risk (endorsement of 2 or more items).</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>High risk: 2 categories positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Low risk: 1 category positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="119"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Actigraphy</title>
        <description>Philips brand Actiwatch Spectrum used to measure total sleep time</description>
        <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.</time_frame>
        <population>N with complete data = 245. N missing = 3.</population>
        <group_list>
          <group group_id="O1">
            <title>Single Group</title>
            <description>Potential participants were screened for eligibility. Upon meeting study eligibility requirements, they were asked to consent. Upon consenting, they were screened additional study requirements before undergoing polysomnography.</description>
          </group>
        </group_list>
        <measure>
          <title>Actigraphy</title>
          <description>Philips brand Actiwatch Spectrum used to measure total sleep time</description>
          <population>N with complete data = 245. N missing = 3.</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="245"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="404.7" spread="74.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Multivariate Apnea Prediction Index (MAPI)</title>
        <description>The questionnaire consists of 3 breathing-related questions and information on demographics (sex, weight, height, age), from which a probability of having sleep apnea (0%-100%) can be calculated. The test-retest reliability of the breathing questions is 0.92 and has a good internal consistency with Cronbach a of 0.85-0.93. A MAPI score of 0.50 (ie, calculated 0% likelihood of having clinically significant sleep apnea with a Respiratory Distress Index&gt;10) has a 0.88 sensitivity and 0.55 specificity.</description>
        <time_frame>During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Group</title>
            <description>Potential participants were screened for eligibility. Upon meeting study eligibility requirements, they were asked to consent. Upon consenting, they were screened additional study requirements before undergoing polysomnography.</description>
          </group>
        </group_list>
        <measure>
          <title>Multivariate Apnea Prediction Index (MAPI)</title>
          <description>The questionnaire consists of 3 breathing-related questions and information on demographics (sex, weight, height, age), from which a probability of having sleep apnea (0%-100%) can be calculated. The test-retest reliability of the breathing questions is 0.92 and has a good internal consistency with Cronbach a of 0.85-0.93. A MAPI score of 0.50 (ie, calculated 0% likelihood of having clinically significant sleep apnea with a Respiratory Distress Index&gt;10) has a 0.88 sensitivity and 0.55 specificity.</description>
          <units>percent probability</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.23" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events time frame was between May 1, 2017 (starting enrollment) until February 1, 2020 (end of study). For each participant, adverse events monitoring occurred between time of study enrollment and either (1) time completed all study procedures, or (2) time participant withdrew from study. The adverse event monitoring period lasted for 2 years and 9 months. For the study sample as a whole, the average monitoring period was 8 days.</time_frame>
      <desc>The definitions used during the study match the clinicaltrials.gov definitions.</desc>
      <group_list>
        <group group_id="E1">
          <title>Single Group</title>
          <description>Potential participants were screened for eligibility. Upon meeting study eligibility requirements, they were asked to consent. Upon consenting, they were screened additional study requirements before undergoing polysomnography.</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="248"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="248"/>
              </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="248"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>The sample may not represent the full population of inpatient rehabilitation patients with TBI; Short lengths of stay impacted study participation; unclear if findings extend to chronic phases of TBI.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Risa Richardson, PhD</name_or_title>
      <organization>James A. Haley Veterans' Hospital</organization>
      <phone>813-972-2000 ext 5309</phone>
      <email>Risa.Richardson@va.gov</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/NCT03033901
org study id: CER-1511-33005
nct id: NCT03033901
lead sponsor: 
collaborator: 
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has dmc: No
Background: Sleep disorders, including sleep apnea, are common after traumatic brain injury
      and affect recovery and negatively influence participation in rehabilitation. Sleep apnea is
      a breathing problem while persons sleep and causes further brain damage and problems with
      thinking, daily functioning, and overall health. Earlier diagnosis and treatment is important
      for traumatic brain injury (TBI) survivors to maximize the recovery process. There is little
      information that guides TBI doctors on how to identify sleep apnea during inpatient TBI
      rehabilitation, a phase in which people experience the potential for a rapid pace of
      improvement. The Agency for Healthcare Research has highlighted gaps in best methods for
      identifying sleep apnea and separately in helping consumers with TBI rehabilitation choices.
      Partnering with survivors, caregivers, and administrators, investigators developed this study
      to compare sleep apnea screening and diagnostic tools in TBI rehabilitation settings. This
      information will provide clinicians, providers, and patients with the best information for
      early identification of sleep apnea to remove negative influence on the pace of recovery in
      early phases after TBI.

      The Goal: Investigators will compare existing screening (Aim 1) and diagnostic tools (Aim 2)
      in TBI patients undergoing inpatient rehabilitation. For the second aim, investigators will
      determine if a more accessible diagnostic test is sufficient to diagnose sleep apnea compared
      to the traditional method used which is less accessible to consumers. If the more accessible
      test is good enough, this will increase recognition of this problem and increase patient
      access to earlier sleep apnea treatment.

      Stakeholders and Products. TBI survivors, caregivers, researchers, and policymakers working
      together on this study helped develop the study questions. Idea exchanges included ways to
      reach clinicians and TBI survivors/caregivers via existing educational programming and online
      tools for consumers such as fact sheets and patient/caregiver-focused videos. Other
      traditional methods will include targeting professional magazines, conferences, and research
      journals that reach professionals working with TBI survivors and their families at the time
      of admission to rehabilitation and during the recovery process. This study will occur at
      rehabilitation hospitals around the country who enroll TBI survivors into a lifetime study
      called the TBI Model System funded by the Department of Health and Human Services and
      Veterans Affairs (VA).
Background and Significance:

      Meta-analyses of TBI studies found prevalence of obstructive sleep apnea (OSA) was 12 times
      higher than community-based studies. Yet, sleep apnea in those with TBI is largely
      undiagnosed. Given that sleep is critical for neural repair and disordered sleep may play a
      role in slowing functional recovery and prolonging rehabilitation, early detection of sleep
      apnea is critical (Stakeholder Input). Minimal guidance exists informing TBI and sleep
      medicine physicians regarding assessment of sleep disorders in the acute rehabilitation
      setting. The Agency for Healthcare Research and Quality's (AHRQ) Comparative Effectiveness
      Review highlighted insufficient comparative effectiveness evidence for diagnostic and
      screening tools. This study proposes to leverage the existing TBI Model System research
      consortium (TBIMS), funded by the Departments of Health and Human Services and Veterans
      Affairs, to improve early detection of sleep apnea in patients with TBI undergoing inpatient
      rehabilitation at six study sites. Study aims are focused around components of phased testing
      for sleep apnea. Findings will inform clinician's decisions for screening and diagnostic
      tests to facilitate earlier recognition of sleep apnea (outcome) and subsequently prescribe
      appropriate treatments.

      Study Aims:

      Aim I: (Screening) For individuals with TBI, determine comparative effectiveness of 2
      American Academy of Sleep Medicine (AASM) endorsed screening tools (STOPBang Questionnaire
      [STOPBang] vs. Actigraphy [ACG]) to identify those at high risk of sleep apnea as diagnosed
      through Level 1 polysomnography (PSG). Long-term Objectives: To inform clinician's choices
      for screening measures to determine presence of sleep apnea.

      Exploratory Aim:

      Evaluate alternative screening tools (Berlin Questionnaire, Multivariate Apnea Prediction
      Index [MAPI]) to Level 1 PSG in Aim 1.

      Aim II: (Diagnosis) This study will determine the diagnostic accuracy (non-inferiority) of
      Level 3 PSG in determining presence of sleep apnea in patients with acute TBI patients in the
      rehabilitation setting. Level 1 PSG will be used as the criterion standard. Long-term
      Objectives: To inform clinician's choices of diagnostic tests to determine presence of sleep
      apnea and prescribe appropriate treatments. If Level 3 portable PSG is equivalent to the less
      accessible Level 1 PSG, this will increase consumer accessibility.

      Study Design:

      This is a 3-year, multi-center prospective observational cohort study.

      Intervention and Comparators:

      In Aim I, the screening tools STOPBang and ACG will be compared against one another to
      determine their sensitivity and specificity in identifying patients with TBI at risk for
      sleep apnea. In Aim II, the non-inferiority of Level 3 PSG in determining presence and
      severity of sleep apnea in patients with moderate to severe TBI will be compared to Level 1
      PSG.

      Study Population:

      Consecutive participants to neurorehabilitation at an existing National Institute on
      Disability, Independent Living, and Rehabilitation Research (NIDILRR) or VA funded TBIMS
      Center will make up the study population. Patients will be age 16 and older (18 or older at
      VA sites), with moderate to severe TBI, admitted for rehabilitation in a U.S. TBIMS inpatient
      rehabilitation facility, and sleeping > 2 hours/night suggesting habitual sleep duration.
      Based on historical data from the six study sites participating in this study, investigators
      in this study conservatively estimated that 70% of patients admitted for inpatient TBI
      rehabilitation would consent into this study (N=20/month), resulting in a 13-month enrollment
      estimate of 259 patients. Power analyses of each study aim suggest that a sample size of 237
      is the largest sample size needed for sufficient power. The sites participating in this study
      aim to collectively enroll 259 patients to account for possible further attrition. Based on
      TBIMS data acquired over the past 25-years, 44% of the sample is female, 64% are categorized
      as Non-White, median age is 38 years, with predominantly moderate to severe TBI.

      Primary outcomes consist of:

      1) Positive predictive power of screening tools: STOPBang and ACG, 2) Equivalency in
      detection of sleep apnea via Level 1 and Level 3 PSG, with diagnosis of sleep apnea based on
      overall apnea-hypopnea index (AHI) > 5.

      Analytic Methods:

      Aim 1: Investigators expect that STOPBang values > 5 and abnormal ACG total sleep time (< 5
      hours with desaturation) will produce sufficiently high SEs with reasonable tradeoff in SP
      (noting that SE and SP are inversely related). Similarly, for Level 1 PSG, a diagnosis of
      sleep apnea will be made if AHI ≥ 5. Cross-tabulations of STOPBang and ACG screening for high
      risk of sleep apnea (positive/negative) versus Level 1 PSG diagnosis (positive/negative) will
      be constructed and estimates of diagnostic accuracy (i.e., sensitivity, specificity, positive
      and negative predictive values, and diagnostic accuracy) will be estimated along with 95%
      confidence intervals. To address hypothesis 1.1, two-sided McNemar's tests will be used to
      compare the paired SEs and paired SPs between STOPBang and ACG assuming a significance level
      of α = 0.05.

      Aim 2: The sensitivity (SE) and specificity (SP) of Level 3 PSG (compared to Level 1 PSG, the
      reference gold standard) will each be estimated and compared to fixed hypothesized rates of
      SE and SP of 90% and 60%, respectively, considered sufficiently large enough. Level 1 PSG
      (reference) diagnosis of sleep apnea will be made based on AHI ≥ 5. Level 3 PSG (test)
      diagnosis will be made based AHI ≥ 5. A cross-tabulation of Level 3 PSG (positive/negative)
      versus Level 1 PSG (positive/negative) will be constructed and standard measures of
      diagnostic accuracy will be estimated along with 95% confidence intervals (i.e., sensitivity,
      specificity, positive and negative predictive values, and diagnostic accuracy).To test for
      non-inferiority of the SE to 90% and the SP to 60%, a non-inferiority threshold of 0.1 is
      assumed. If the lower bound on the 95% confidence interval for SE is strictly above 80% and
      the lower bound on the confidence interval for SP is strictly above 50% then non-inferiority
      of Level 3 PSG (compared to Level 3 PSG) can be established.
observational model: Cohort
time perspective: Prospective
measure: Apnea-Hypopnea Index (AHI)
time frame: During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-traumatic brain injury (TBI) in civilian settings and 132 days in Veterans Affairs (VA) settings.
description: A diagnosis of sleep apnea will be determined by overall apnea-hypopnea index (AHI) greater or equal to 5 and greater than or equal to 15 denoting different severity levels of disease.
measure: STOPBang Sleep Apnea Risk
time frame: During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.
description: Sleep apnea screening measure. Risk based on responses to 8 items (2,low risk; 3-4, intermediate risk; >5, high risk).
measure: Berlin Sleep Apnea Risk
time frame: During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.
description: Sleep apnea screening measure with 10-items. Risk stratification is based on number of items: no risk (no items endorsed), low (endorsement of 1 item) or high risk (endorsement of 2 or more items).
measure: Actigraphy
time frame: During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.
description: Philips brand Actiwatch Spectrum used to measure total sleep time
measure: Multivariate Apnea Prediction Index (MAPI)
time frame: During inpatient brain injury rehabilitation, which can occur on average (median) up to 37 days post-TBI in civilian settings and 132 days in VA settings.
description: The questionnaire consists of 3 breathing-related questions and information on demographics (sex, weight, height, age), from which a probability of having sleep apnea (0%-100%) can be calculated. The test-retest reliability of the breathing questions is 0.92 and has a good internal consistency with Cronbach a of 0.85-0.93. A MAPI score of 0.50 (ie, calculated 0% likelihood of having clinically significant sleep apnea with a Respiratory Distress Index>10) has a 0.88 sensitivity and 0.55 specificity.
intervention type: Device
intervention name: Polysomnography - Level 1 and Level 3
description: Participants will undergo simultaneous administration of Level 1 and 3 polysomnography on the rehabilitation unit with study funded sleep technologist present to meet Level 1 standards.
other name: Philips Respironics Alice 6 Lab Diagnostic System
other name: Nox T3
intervention type: Device
intervention name: Actigraphy monitoring
description: Participants will undergo actigraphy monitoring to assess habitual sleep duration to determine readiness for polysomnography and examine trajectory and duration of sleep.
other name: Philips Respironics Airway (AW) Spectrum Plus Actiwatch
intervention type: Other
intervention name: Sleep Apnea Screening
description: Participants and their family member or proxy, and clinical staff will be asked to answer questions in order to complete the three standardized sleep apnea screening measures.
other name: Berlin Questionnaire
other name: STOPBang Questionnaire
other name: Multivariate Apnea Prediction Index
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Risa Richardson, PhD
role: Principal Investigator
affiliation: James A. Haley Veterans' Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://www.tbindsc.org/
description: NIDILRR-funded TBI Model System website
citation: Holcomb EM, Schwartz DJ, McCarthy M, Thomas B, Barnett SD, Nakase-Richardson R. Incidence, Characterization, and Predictors of Sleep Apnea in Consecutive Brain Injury Rehabilitation Admissions. J Head Trauma Rehabil. 2016 Mar-Apr;31(2):82-100. doi: 10.1097/HTR.0000000000000230.
PMID: 26959663
citation: Kamper JE, Garofano J, Schwartz DJ, Silva MA, Zeitzer J, Modarres M, Barnett SD, Nakase-Richardson R. Concordance of Actigraphy With Polysomnography in Traumatic Brain Injury Neurorehabilitation Admissions. J Head Trauma Rehabil. 2016 Mar-Apr;31(2):117-25. doi: 10.1097/HTR.0000000000000215.
PMID: 26959665
citation: Towns SJ, Zeitzer J, Kamper J, Holcomb E, Silva MA, Schwartz DJ, Nakase-Richardson R. Implementation of Actigraphy in Acute Traumatic Brain Injury (TBI) Neurorehabilitation Admissions: A Veterans Administration TBI Model Systems Feasibility Study. PM R. 2016 Nov;8(11):1046-1054. doi: 10.1016/j.pmrj.2016.04.005. Epub 2016 May 10.
PMID: 27178377
citation: Nakase-Richardson R. Improving the Significance and Direction of Sleep Management in Traumatic Brain Injury. J Head Trauma Rehabil. 2016 Mar-Apr;31(2):79-81. doi: 10.1097/HTR.0000000000000235. No abstract available.
PMID: 26959662
citation: Holcomb EM, Towns S, Kamper JE, Barnett SD, Sherer M, Evans C, Nakase-Richardson R. The Relationship Between Sleep-Wake Cycle Disturbance and Trajectory of Cognitive Recovery During Acute Traumatic Brain Injury. J Head Trauma Rehabil. 2016 Mar-Apr;31(2):108-16. doi: 10.1097/HTR.0000000000000206.
PMID: 26709584
citation: Nakase-Richardson R, Sherer M, Barnett SD, Yablon SA, Evans CC, Kretzmer T, Schwartz DJ, Modarres M. Prospective evaluation of the nature, course, and impact of acute sleep abnormality after traumatic brain injury. Arch Phys Med Rehabil. 2013 May;94(5):875-82. doi: 10.1016/j.apmr.2013.01.001. Epub 2013 Jan 4.
PMID: 23296143
citation: Silva MA, Nakase-Richardson R, Sherer M, Barnett SD, Evans CC, Yablon SA. Posttraumatic confusion predicts patient cooperation during traumatic brain injury rehabilitation. Am J Phys Med Rehabil. 2012 Oct;91(10):890-3. doi: 10.1097/PHM.0b013e31825a1648.
PMID: 22660372
citation: Nakase-Thompson R, Sherer M, Yablon SA, Nick TG, Trzepacz PT. Acute confusion following traumatic brain injury. Brain Inj. 2004 Feb;18(2):131-42. doi: 10.1080/0269905031000149542.
PMID: 14660226
citation: Nakase-Richardson R, Dahdah MN, Almeida E, Ricketti P, Silva MA, Calero K, Magalang U, Schwartz DJ. Concordance between current American Academy of Sleep Medicine and Centers for Medicare and Medicare scoring criteria for obstructive sleep apnea in hospitalized persons with traumatic brain injury: a VA TBI Model System study. J Clin Sleep Med. 2020 Jun 15;16(6):879-888. doi: 10.5664/jcsm.8352.
PMID: 32043962
citation: Nakase-Richardson R, Schwartz DJ, Ketchum JM, Drasher-Phillips L, Dahdah MN, Monden KR, Bell K, Hoffman J, Whyte J, Bogner J, Calero K, Magalang U. Comparison of Diagnostic Sleep Studies in Hospitalized Neurorehabilitation Patients With Moderate to Severe Traumatic Brain Injury. Chest. 2020 Oct;158(4):1689-1700. doi: 10.1016/j.chest.2020.03.083. Epub 2020 May 6.
PMID: 32387522
citation: Nakase-Richardson R, Hoffman JM, Magalang U, Almeida E, Schwartz DJ, Drasher-Phillips L, Ketchum JM, Whyte J, Bogner J, Dismuke-Greer CE. Cost-Benefit Analysis From the Payor's Perspective for Screening and Diagnosing Obstructive Sleep Apnea During Inpatient Rehabilitation for Moderate to Severe TBI. Arch Phys Med Rehabil. 2020 Sep;101(9):1497-1508. doi: 10.1016/j.apmr.2020.03.020. Epub 2020 May 4. Erratum In: Arch Phys Med Rehabil. 2021 Mar;102(3):561.
PMID: 32376325
citation: Zeitzer JM, Hon F, Whyte J, Monden KR, Bogner J, Dahdah M, Wittine L, Bell KR, Nakase-Richardson R. Coherence Between Sleep Detection by Actigraphy and Polysomnography in a Multi-Center, Inpatient Cohort of Individuals with Traumatic Brain Injury. PM R. 2020 Dec;12(12):1205-1213. doi: 10.1002/pmrj.12353. Epub 2020 Mar 26.
PMID: 32125095
responsible party type: Sponsor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
sharing ipd: Yes
ipd description: Final de-identified data sets underlying publications resulting from the proposed research will be available outside VA in electronic format, through email upon request, after results are published. Data sets will be available for collaborators and other investigators upon request prior to publication (expected time period: 120 days post request). The extent of the data will be de-identified aggregate data only.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data will be available upon request following publication of the primary aims. Data will be made available while the Institutional Review Board (IRB) protocol remains active.
ipd access criteria: Data requests will be reviewed by the Study PI and responded to within 120 days of request. Data requests will follow the TBI Model System External Request Standard Operating Procedure (SOP) which is available at www.tbindsc.org.
ipd url: http://www.tbindsc.org
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The sample may not represent the full population of inpatient rehabilitation patients with TBI; Short lengths of stay impacted study participation; unclear if findings extend to chronic phases of TBI.
point of contact: 