Apnea, SleepC-SASNCT03033901
Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome
An observational study of Apnea, Sleep and Brain Injury, Traumatic, run by James A. Haley Veterans Administration Hospital at 6 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Apnea, Sleep, Brain Injury, Traumatic
- What is being tested?
- Polysomnography - Level 1 and Level 3, Actigraphy monitoring and Sleep Apnea Screening
- Type of treatment
- Medical device
- How many people
- 345 participants
- Where
- 6 sitesUnited States
- Study dates
- 1 May 2017to 1 Feb 2020
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study population will be TBI patients admitted to inpatient rehabilitation at an existing NIDILRR or VA funded TBI Model System Center who meet study inclusion and exclusion criteria.
Who may be able to join
- Meet case definition for TBI:
- (A). VA (for James A. Haley Veterans' Hospital): i. Persons fitting the definition of traumatic brain injury (TBI), defined as a traumatically induced structural brain injury, brain trauma, or damage to brain tissue, and/or physiological disruption of brain function as a result of an external mechanical force (also including acceleration/deceleration movement without direct external trauma to the head, a foreign body penetrating the brain, forces generated from events such as a blast or explosion, or other force) as evidenced by self-reported or medically documented (physical examination or mental status examination) new onset or worsening of at least one of the following clinical signs immediately following the event: (a) a period of loss of or a decreased level of consciousness; (b) alteration in mental state at the time of the injury (confusion, disorientation, slowed thinking); (c) loss of memory for events immediately before or after the injury; (d) posttraumatic amnesia (PTA); (d)neurological deficits (weakness, imbalance, change in vision, praxis, paresis/plegia, sensory loss, aphasia, etc.) that may or may not be transient; or (e) intracranial lesion. ii. Age 18 or older at the time of index TBI. iii. Admitted to one of the five designated VA Polytrauma Rehabilitation Centers (PRCs) for comprehensive rehabilitation with the presenting diagnoses of TBI. Comprehensive rehabilitation must occur in the PRC and meet the following criteria: (a) Medical and rehabilitation care are supervised on a regular basis by a physician affiliated with the PRC; (b) 24-hour nursing care is provided to the patient; (c) Physical Therapy (PT), Occupational Therapy (OT), Speech, Rehabilitation Psychology, Neuropsychology, and/or family support/education are provided in an integrated team approach with the expectation of further gain; (d) Operates in a manner consistent with Commission on Accreditation of Rehabilitation Facilities (CARF) standards for brain injury inpatient rehabilitation and/or Medicare requirements for inpatient rehabilitation.
- OR
- (B). Civilian (for civilian sites): Damage to brain tissue caused by an external mechanical force, alteration of consciousness > 24 hours, or loss of consciousness >30 minutes, or Glasgow Coma Scale (GCS) score in the Emergency Department of3-12, or intracranial abnormalities on imaging regardless of GCS;
- AND
- admission to an inpatient brain injury rehabilitation program;
Show all 10Show fewer
- minimum age 16 years at civilian sites and 18 years at the VA site;
- Understands and provides informed consent to participate (or, if unable, healthcare proxy / legal guardian understands and provides informed consent for the patient);
- sleep duration > 2 hours/night.
- Although not specifically targeted, pregnant women and people with intellectual developmental disorders or prior psychiatric histories meeting the above inclusion/exclusion criteria can be enrolled in this study. Individuals with known history of sleep apnea will be eligible for the study and apnea status will be reconfirmed with new diagnostic study.
Who cannot join
- persons less than 16 years old at civilian sites and less than 18 years old at VA site will not be included;
- pre-injury diagnosis of narcolepsy or persistent daytime somnolence as documented in patient's medical record and/or family report; and/or
- tracheostomy placed and decannulation or overnight capping of the tracheostomy not feasible during rehabilitation hospitalization.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
The Ohio State University
Columbus, Ohio, 43210
Baylor Institute for Rehabilitation
Dallas, Texas, 75246
Albert Einstein Healthcare Network/Moss Rehabilitation Hospital
Elkins Park, Pennsylvania, 19027
Craig Hospital
Englewood, Colorado, 80113
University of Washington
Seattle, Washington, 98104
James A. Haley Veterans' Hospital
Tampa, Florida, 33612
About this study
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).
Read the detailed description
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:
- 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.
- Conditions
- Apnea, Sleep, Brain Injury, Traumatic
- Being tested
- Polysomnography - Level 1 and Level 3, Actigraphy monitoring, Sleep Apnea Screening
- Keywords
- Veterans, Comparative Effectiveness Research, Diagnosis
- Medical subject headings
- Sleep Apnea Syndromes, Brain Injuries, Traumatic, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Polysomnography - Level 1 and Level 3Device
Also called Philips Respironics Alice 6 Lab Diagnostic System, Nox T3
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.
Actigraphy monitoringDevice
Also called Philips Respironics Airway (AW) Spectrum Plus Actiwatch
Participants will undergo actigraphy monitoring to assess habitual sleep duration to determine readiness for polysomnography and examine trajectory and duration of sleep.
Sleep Apnea ScreeningOther
Also called Berlin Questionnaire, STOPBang Questionnaire, Multivariate Apnea Prediction Index
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
Apnea-Hypopnea Index (AHI)
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2017 (estimated)
- Study start1 May 2017
- Primary completion1 Feb 2020
- Study completion1 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Apnea, SleepStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 345 participants (actual)
Sponsor and investigators
- Lead sponsor
- James A. Haley Veterans Administration Hospital
- Sponsor type
- US federal agency
- Collaborators
- Patient-Centered Outcomes Research Institute, Craig Hospital, Moss Rehabilitation Research Institute, University of Washington, Baylor Institute for Rehabilitation, Ohio State University, University of South Florida, Palo Alto Veterans Institute for Research, North Florida Foundation for Research and Education
- Responsible party
- Sponsor
- Investigators
- Risa Richardson, PhD, Principal investigator, James A. Haley Veterans' Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03033901
- Sponsor's protocol ID
- CER-1511-33005
- Acronym
- C-SAS
- Status last verified
- Mar 2023
- First submitted
- 18 Jan 2017
- Last updated
- 29 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 26959663Kamper 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.
PubMed 26959665Towns 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.
PubMed 27178377Nakase-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.
PubMed 26959662Holcomb 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.
PubMed 26709584Nakase-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.
PubMed 23296143Silva 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.
PubMed 22660372Nakase-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.
PubMed 14660226Nakase-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.
PubMed 32043962Nakase-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.
PubMed 32387522Nakase-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.
PubMed 32376325Zeitzer 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.
PubMed 32125095Martin AM, Pinto SM, Tang X, Hoffman JM, Wittine L, Walker WC, Schwartz DJ, Kane G, Takagishi SC, Nakase-Richardson R. Associations between early sleep-disordered breathing following moderate-to-severe traumatic brain injury and long-term chronic pain status: a Traumatic Brain Injury Model Systems study. J Clin Sleep Med. 2023 Jan 1;19(1):135-143. doi: 10.5664/jcsm.10278.
PubMed 36591795Steward KA, Silva MA, Maduri P, Tang X, Wittine L, Dams-O'Connor K, Nakase-Richardson R. Obstructive sleep apnea is associated with worse cognitive outcomes in acute moderate-to-severe traumatic brain injury: A TBI Model Systems study. Sleep Med. 2022 Dec;100:454-461. doi: 10.1016/j.sleep.2022.09.012. Epub 2022 Oct 5.
PubMed 36252414Martin AM, Almeida EJ, Starosta AJ, Hammond FM, Hoffman JM, Schwartz DJ, Fann JR, Bell KR, Nakase-Richardson R. The Impact of Opioid Medications on Sleep Architecture and Nocturnal Respiration During Acute Recovery From Moderate to Severe Traumatic Brain Injury: A TBI Model Systems Study. J Head Trauma Rehabil. 2021 Sep-Oct 01;36(5):374-387. doi: 10.1097/HTR.0000000000000727.
PubMed 34489388
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome
- ClinicalTrials.gov ID
- NCT03033901
- Acronym / sponsor ID
- C-SAS / CER-1511-33005
- Conditions
- Apnea, Sleep, Brain Injury, Traumatic
- Keywords
- Veterans, Comparative Effectiveness Research, Diagnosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 345 participants (actual)
- Lead sponsor
- James A. Haley Veterans Administration HospitalUS federal agency
- Collaborators
- Patient-Centered Outcomes Research Institute, Craig Hospital, Moss Rehabilitation Research Institute, University of Washington, Baylor Institute for Rehabilitation, Ohio State University, University of South Florida, Palo Alto Veterans Institute for Research, North Florida Foundation for Research and Education
- Study start
- 1 May 2017 (actual)
- Primary completion
- 1 Feb 2020 (actual)
- Study completion
- 1 Feb 2020 (actual)
- First posted
- 27 Jan 2017 (estimated)
- Results
- Posted 29 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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:
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population will be TBI patients admitted to inpatient rehabilitation at an existing NIDILRR or VA funded TBI Model System Center who meet study inclusion and exclusion criteria.
Key inclusion criteria (10 listed)
- Meet case definition for TBI:
- (A). VA (for James A. Haley Veterans' Hospital): i. Persons fitting the definition of traumatic brain injury (TBI), defined as a traumatically induced structural brain injury, brain trauma, or damage to brain tissue, and/or physiological disruption of brain function as a result of an external mechanical force (also including acceleration/deceleration movement without direct external trauma to the head, a foreign body penetrating the brain, forces generated from events such as a blast or explosion, or other force) as evidenced by self-reported or medically documented (physical examination or mental status examination) new onset or worsening of at least one of the following clinical signs immediately following the event: (a) a period of loss of or a decreased level of consciousness; (b) alteration in mental state at the time of the injury (confusion, disorientation, slowed thinking); (c) loss of memory for events immediately before or after the injury; (d) posttraumatic amnesia (PTA); (d)neurological deficits (weakness, imbalance, change in vision, praxis, paresis/plegia, sensory loss, aphasia, etc.) that may or may not be transient; or (e) intracranial lesion. ii. Age 18 or older at the time of index TBI. iii. Admitted to one of the five designated VA Polytrauma Rehabilitation Centers (PRCs) for comprehensive rehabilitation with the presenting diagnoses of TBI. Comprehensive rehabilitation must occur in the PRC and meet the following criteria: (a) Medical and rehabilitation care are supervised on a regular basis by a physician affiliated with the PRC; (b) 24-hour nursing care is provided to the patient; (c) Physical Therapy (PT), Occupational Therapy (OT), Speech, Rehabilitation Psychology, Neuropsychology, and/or family support/education are provided in an integrated team approach with the expectation of further gain; (d) Operates in a manner consistent with Commission on Accreditation of Rehabilitation Facilities (CARF) standards for brain injury inpatient rehabilitation and/or Medicare requirements for inpatient rehabilitation.
- OR
- (B). Civilian (for civilian sites): Damage to brain tissue caused by an external mechanical force, alteration of consciousness > 24 hours, or loss of consciousness >30 minutes, or Glasgow Coma Scale (GCS) score in the Emergency Department of3-12, or intracranial abnormalities on imaging regardless of GCS;
- AND
Key exclusion criteria (3 listed)
- persons less than 16 years old at civilian sites and less than 18 years old at VA site will not be included;
- pre-injury diagnosis of narcolepsy or persistent daytime somnolence as documented in patient's medical record and/or family report; and/or
- tracheostomy placed and decannulation or overnight capping of the tracheostomy not feasible during rehabilitation hospitalization.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Polysomnography - Level 1 and Level 3Also: Philips Respironics Alice 6 Lab Diagnostic System, Nox T3Participants 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. | Device | – |
| Actigraphy monitoringAlso: Philips Respironics Airway (AW) Spectrum Plus ActiwatchParticipants will undergo actigraphy monitoring to assess habitual sleep duration to determine readiness for polysomnography and examine trajectory and duration of sleep. | Device | – |
| Sleep Apnea ScreeningAlso: Berlin Questionnaire, STOPBang Questionnaire, Multivariate Apnea Prediction IndexParticipants 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 | – |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26959663Holcomb 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.
- Background: PubMed 26959665Kamper 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.
- Background: PubMed 27178377Towns 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.
- Background: PubMed 26959662Nakase-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.
- Background: PubMed 26709584Holcomb 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.
- Background: PubMed 23296143Nakase-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.
- Background: PubMed 22660372Silva 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.
- Background: PubMed 14660226Nakase-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.
- Background: PubMed 32043962Nakase-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.
- Background: PubMed 32387522Nakase-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.
- Background: PubMed 32376325Nakase-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.
- Background: PubMed 32125095Zeitzer 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.
- NIDILRR-funded TBI Model System websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Risa Richardson, PhD principal investigator
James A. Haley Veterans' Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Apnea, Sleep and Brain Injury, Traumatic, run by James A. Haley Veterans Administration Hospital at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03033901, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2023.