Deployment of a Novel National Institute of Neurological Disorders and Stroke Clinical, Biomarker, Imaging, and Modifiers (CBI-M) Classification Framework for Emergency Department Patients With Glasgow Coma Scale 15 Traumatic Brain Injury (PIONEER-Prognosis)

The PIONEER-Prognosis Study is a prospective, multicenter, observational cohort study of adults aged 18 to 65 years who present to the emergency department (ED) within 24 hours of a mild traumatic brain injury (TBI) and have a Glasgow Coma Scale (GCS) score of 15, meaning they are fully alert. Although these injuries are classified as mild, up to half of such patients report persistent symptoms such as headaches, cognitive difficulties, and mood disturbances a year after injury, and clinicians currently lack a reliable way to predict, at the time of the ED visit, which patients will recover fully and which will not.

This study will apply a new classification framework proposed by the National Institute of Neurological Disorders and Stroke (NINDS), called Clinical, Biomarker, Imaging, and Modifiers (CBI-M). This framework combines clinical findings; blood tests for two brain injury proteins, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1); results of any head computed tomography (CT) scan performed as part of routine care; and psychosocial and environmental factors. The study will evaluate how well this framework predicts recovery.

A total of 500 participants will be enrolled from five EDs in Michigan, Oregon, and California that already use GFAP and UCH-L1 blood tests in clinical care. Participants will provide a blood sample and clinical information during their ED visit, wear a WHOOP wearable device continuously for 90 days to record heart rate, heart rate variability, sleep, and physical activity, complete a brief daily symptom survey through the device application, and complete additional symptom and sleep questionnaires by email or phone at 1 week, 1 month, and 2 months.

Trained interviewers from a central outcomes team will contact participants by telephone at 14 and 90 days to assess functional recovery using the Glasgow Outcome Scale-Extended (GOS-E), along with symptoms, cognition, life satisfaction, post-traumatic stress symptoms, and resilience.

The primary outcome is complete functional recovery, defined as a GOS-E score of 8 at 90 days. The study does not assign any treatment; participants receive standard ED care. Findings are intended to improve prognostic accuracy, patient counseling, and follow-up care for the largest subgroup of patients with TBI. The prediction models developed will be made available as a free web-based tool. The study is funded by the U.S. Department of Defense and is expected to take approximately 4 years to complete, with each participant followed for 3 months.

Patients presenting to a study emergency department with a Glasgow Coma Scale (GCS) score of 15 and traumatic brain injury (TBI).

Plazo: 3 months

Functional recovery will be assessed using the Glasgow Outcome Scale-Extended (GOS-E). The GOS-E rates patient status on one of eight levels. The minimum score is 1 and the maximum score is 8: 1 = death; 2 = vegetative state; 3 = lower severe disability; 4 = upper severe disability; 5 = lower moderate disability; 6 = upper moderate disability; 7 = lower good recovery; and 8 = upper good recovery.

Plazo: Up to 90 days

Daily symptom burden will be measured using five commonly endorsed items-fatigue, headache, poor concentration, frustration, and sleep problems-from the Rivermead Post-Concussion Questionnaire (RPQ), a validated instrument that assesses post-concussive symptom severity. Each symptom is rated from 0 to 4, with 0 indicating that the symptom is not experienced and 4 indicating a severe problem. Scores for the five items are summed to yield a total score ranging from 0 to 20, with higher scores indicating greater daily post-concussive symptom burden.

Plazo: Up to 90 days

HRV will be continuously measured using the WHOOP wearable device. HRV will be reported in milliseconds (ms) and reflects variation in the time intervals between successive heartbeats. HRV is a continuous physiological measure with no predefined minimum or maximum value. Higher or lower HRV values are not inherently classified as better or worse outcomes; values will be evaluated as physiological measures in relation to recovery following traumatic brain injury.

Plazo: Up to 90 days

Physiological outcomes will be continuously measured via the WHOOP wearable device. WHOOP is a wearable health and fitness tracker that continuously monitors key physiological metrics

Plazo: Up to 90 days

Sleep duration will be continuously measured using the WHOOP wearable device. WHOOP is a wearable health and fitness tracker that continuously monitors key physiological metrics.

Plazo: Up to 90 days

Sleep efficiency will be continuously measured using the WHOOP wearable device. WHOOP is a wearable health and fitness tracker that continuously monitors key physiological metrics.

Plazo: Up to 90 days

Sleep latency will be continuously measured using the WHOOP wearable device. WHOOP is a wearable health and fitness tracker that continuously monitors key physiological metrics.

Plazo: Up to 90 days

Total amount of sleep will be continuously measured using the WHOOP wearable device. WHOOP is a wearable health and fitness tracker that continuously monitors key physiological metrics.

Plazo: Up to 90 days

Percentage of restorative sleep will be continuously measured using the WHOOP wearable device. WHOOP is a wearable health and fitness tracker that continuously monitors key physiological metrics.

Plazo: Up to 90 days

Strain will be continuously measured using the WHOOP wearable device. WHOOP is a wearable health and fitness tracker that continuously monitors key physiological metrics.

Plazo: Up to 90 days

Body temperature will be continuously measured using the WHOOP wearable device. WHOOP is a wearable health and fitness tracker that continuously monitors key physiological metrics. ClinicalTrials.gov PRS\_ Protoco…

Plazo: Up to 90 days

Oxygen saturation will be continuously measured using the WHOOP wearable device. WHOOP is a wearable health and fitness tracker that continuously monitors key physiological metrics.

Plazo: Up to 2 months

Post-concussive symptoms will be assessed using the Rivermead Post-Concussion Questionnaire (RPQ). The RPQ assesses 16 common post-concussive symptoms, with each symptom rated from 0 to 4, where 0 indicates that the symptom is not experienced, 1 indicates no more of a problem than before the injury, and 2-4 indicate mild, moderate, or severe problems, respectively. For standard scoring, responses of 1 are scored as 0, resulting in a total score ranging from 0 to 64. Higher scores indicate greater post-concussive symptom burden and therefore a worse outcome.

Deployment of a Novel NINDS Clinical, Biomarker, Imaging, and Modifiers (CBI-M) Classification Framework for ED Patients With GCS 15 TBI (PIONEER-Prognosis)