Precision Biomarkers to Detect Brain Injury in Active-Duty United States Special Operations Forces With Repeated Blast Exposure

NCT07131475 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2025P000608H9240525FE002
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 4-year, longitudinal study of 100 active-duty Navy SEALs. The goal of the study is to determine whether repeated blast exposure affects SEAL brain health and to develop an initial diagnostic testing protocol that detects repeated blast brain injury.

Conditions

Blast Injury

Keywords

repeated blast exposure; Special Operations Forces; traumatic brain injury

Outcome Measures

Primary Outcomes (3)

• neuroimaging biomarkers

  TSPO tracer uptake within the brain on TSPO PET, functional connectivity of the executive control, default and salience networks on resting-state functional MRI and diffusion MRI, and brain signal abnormalities on multidimensional MRI

  1 year

• blood biomarkers

  tau, ptau, bd-tau, NF-L, GFAP, UCH-L1, IL-6, IL-10, TNF alpha

  1 year

• neuropsychiatric symptoms

  Neurobehavioral Symptom Inventory

  1 year

Study Arms (1)

Active-duty United States Navy SEALs

EXPERIMENTAL

All SEAL participants will undergo comprehensive, longitudinal assessments of their exposures, cognitive performance, psychological health, physical symptoms, neuroimaging biomarkers, and blood biomarkers.

Drug: PBR28 TSPO PET

Interventions

PBR28 TSPO PET DRUG

Each SEAL participant will undergo brain imaging with PBR28 translocator protein (TSPO) positron emission tomography (PET) at study enrollment and at 1-year follow up.

Active-duty United States Navy SEALs

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Active-duty Navy SEAL Service Member
• Early career SEAL (0-2 years) or mid-late career SEAL (10-15 years)
• Age 18-50 years
• Males, regardless of race or ethnicity

You may not qualify if:

• History of moderate or severe TBI
• History of major neurological disorder
• Untreated or unstable severe psychiatric condition
• Current severe medical condition that requires long-term treatment
• Any condition that may cause undue risk to the participant or create a logistical contraindication
• MRI contraindication
• PET contraindication

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• University of South Florida: collaborator
• Navy SEAL Foundation: collaborator
• National Institutes of Health (NIH): collaborator
• Uniformed Services University of the Health Sciences: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (1)

• Gilmore N, Tseng CJ, Maffei C, Tromly SL, Deary KB, McKinney IR, Kelemen JN, Healy BC, Hu CG, Ramos-Llorden G, Masood M, Cali RJ, Guo J, Belanger HG, Yao EF, Baxter T, Fischl B, Foulkes AS, Polimeni JR, Rosen BR, Perl DP, Hooker JM, Zurcher NR, Huang SY, Kimberly WT, Greve DN, Mac Donald CL, Dams-O'Connor K, Bodien YG, Edlow BL. Impact of repeated blast exposure on active-duty United States Special Operations Forces. Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2313568121. doi: 10.1073/pnas.2313568121. Epub 2024 Apr 22.

  PMID: 38648470 BACKGROUND

MeSH Terms

Conditions

Blast Injuries; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Barotrauma; Wounds and Injuries; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System

Central Study Contacts

Brian L Edlow, M.D.

CONTACT

617-724-6352; bedlow@mgh.harvard.edu

Michael A Gordon, B.s.

CONTACT

617-724-6352; magordon@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: The investigators analyzing the MRI, cognitive, psychological, physical symptom, and exposure data will be blinded to the PRB28 TSPO PET results. Similarly, the investigators analyzing the PBR28 TSPO PET results will be blinded to all other data elements. The participants will be also be blinded to PBR28 TSPO PET results.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This diagnostic study of a single group - active-duty United States Navy SEALs -will utilize PBR28 TSPO PET. Use of the PBR tracer is overseen by the U.S. FDA. Thus, this study is considered "interventional". However, given that the purpose of the study is to develop an initial diagnostic testing protocol for repeated blast brain injury, the typical Phase criteria for therapeutic trials do not apply here. We have selected "Phase 2" from the required list of choices, because the safety of the PRB tracer has been previously established (hence Phase 1 is not appropriate) and because this is not a definitive efficacy study (hence Phase 3 is not appropriate).

Study Record Dates

• First Submitted: July 24, 2025
• First Posted: August 20, 2025
• Study Start: October 14, 2025
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)