BRIDGE-US: Bridging Readiness in Deployed Neurotrauma Gaps for Excellence (BRIDGE-US)

The purpose of this research study is to prospectively collect biospecimens, imaging, and clinical data from patients with penetrating brain injuries across high-volume PBI sites in the US (including UChicago). Biospecimens will undergo biomarker analysis - biomarker data specific to PBI is extremely limited, and could provide critical insight to outcome identification and clinical decision making.

This data will be used to build the first comprehensive PBI Data Commons, biorepository, and imaging repository which will create the infrastructure necessary to close critical knowledge gaps, advance biomarker discovery specific to PBI, and provide the foundation for future research aimed at improving prognostication and treatment for patients with this devastating injury.

Study Overview

• Status: Not yet recruiting
• Conditions: Traumatic Brain Injury; Brain Trauma; Penetrating Head Injury; Brain Injuries, Acute
• Intervention / Treatment: Other: Blood Sample Collection

Detailed Description

Penetrating brain injury (PBI) is one of the most devastating and understudied forms of traumatic brain injury (TBI), characterized by the violation of the skull and brain parenchyma by foreign objects such as bullets or shrapnel. Unlike blunt TBI, PBI involves unique mechanical and secondary injury patterns, including direct tissue destruction, vascular damage, hemorrhage, cavitation, and axonal shearing. These injuries often lead to severe disability or death, particularly in military and civilian populations exposed to ballistic trauma. Despite the increasing burden of firearm-related PBI in civilian trauma centers and the operational relevance in military settings, there remains a significant lack of structured data, standardized terminology, and biological understanding to guide prognostication or treatment decisions. This knowledge gap has fostered therapeutic nihilism, resulting in high rates of early withdrawal of life-sustaining therapies and a lack of targeted clinical pathways for these patients.

Emerging biomarker research in blunt TBI has identified several promising molecular indicators that reflect different aspects of brain injury. These include S100 calcium-binding protein B (S100B), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NFL), which are associated with glial activation, neuronal injury, and axonal damage, respectively. Elevated levels of GFAP and UCH-L1, for example, have been correlated with injury severity and poor outcomes in both civilian and military TBI populations, while NFL has shown potential as a predictor of long-term cognitive deficits. However, biomarker data specific to PBI is extremely limited. The distinct mechanical forces and injury patterns of PBI suggest that biomarker profiles may differ significantly from those seen in blunt trauma, highlighting the need for focused investigation. The temporal profiles of biomarkers have been assessed in blunt TBI but not in PBI. Advancing biomarker discovery in PBI could help identify patients at risk of poor outcomes, support early clinical decision-making, and differentiate PBI from overlapping conditions.

Beyond molecular markers, imaging plays a critical role in the diagnosis and management of PBI. High-resolution structural imaging, including computed tomography (CT) and advanced magnetic resonance imaging (MRI) techniques such as diffusion tensor imaging (DTI), provides critical insights into the extent of parenchymal damage, vascular injury, and axonal disruption. However, imaging access is often limited in prehospital or austere environments, especially in military settings. A combined approach leveraging clinical data, biomarkers, and imaging holds promise for improving the characterization of PBI and guiding treatment decisions across care environments.

The study's integrated approach will create the infrastructure necessary to close critical knowledge gaps, advance biomarker discovery specific to PBI, and provide the foundation for future research aimed at improving prognostication and treatment for patients with this devastating injury.

• Study Type: Observational
• Enrollment (Estimated): 270

Contacts and Locations

• Study Contact: Name: Hugh Flynn; Phone Number: 773-834-9627; Email: Hugh.Flynn@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
      • Contact: Hugh Flynn; Phone Number: 773-834-9627; Email: Hugh.Flynn@bsd.uchicago.edu
      • Contact: Hugh Flynn; Email: Hugh.Flynn@bsd.uchicago.edu
      • Principal Investigator: Susan Rowell, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects with confirmed PBI.

Description

Inclusion Criteria:

1. Age: Subjects aged 16 years and older
2. Injury Type/Evidence: Patients with a confirmed PBI as demonstrated by head imaging or physical exam (evidence of dural penetration by a projectile)
3. Timeframe: Patients must be enrolled within 8 hours of injury

Exclusion Criteria:

No subjects will be excluded based on gender or ethnicity for this study. Subjects under the age of 16 will be excluded. These subjects differ significantly in terms of neurodevelopment, physiology, and trauma response, which introduces heterogeneity that could confound study results. Additionally, pediatric PBI has distinct etiologies, treatment pathways, and prognostic indicators compared to adult PBI (note that age 16 and up are treated medically as adults).

FULL EXCLUSION CRITERIA:

1. Dead on Arrival (DOA): Patients who receive CPR with no return of pulse
2. Non-penetrating injury: Patients with head injuries that do not include dural penetration
3. Polytrauma: Patients with penetrating or blunt injuries to other parts of the body
4. Known or suspected pregnancy
5. Known or suspected prisoner

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Building the first PBI Data Commons, Biorepository, and Imaging Repository	The primary objective of this prospective study is to build the first comprehensive PBI Data Commons, Biorepository, and Imaging Repository. Clinical data, biospecimens, and imaging from subjects with PBI will be prospectively collected and analyzed across multiple sites, which will then be used to build these resources.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative biomarker analysis using validated laboratory assays conducted at Orlando Health and Mayo Clinic Laboratories.	Biospecimens will undergo biomarker analysis. This will provide another critical layer of information in the repositories for future studies aiming to improve rapid detection, diagnosis, prognostication, and outcome for casualties with PBI.	3 months

Collaborators and Investigators

• Sponsor: University of Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2035

Study Registration Dates

• First Submitted: May 7, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds, Penetrating; Brain Injuries, Traumatic; Brain Injuries; Head Injuries, Penetrating
• Other Study ID Numbers: IRB25-0888; Medical Technology Enterprise (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No