Brain Imaging for Traumatic Brain Injury

Overseen By Michael A Gordon, B.s.

Age: 18 - 65

Sex: Male

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Disqualifiers: Moderate/severe TBI, Neurological disorder, Severe psychiatric, Severe medical, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how repeated exposure to blasts affects the brain health of Navy SEALs. Researchers will use a special brain imaging technique, PBR28 TSPO PET (a type of positron emission tomography scan), to detect signs of brain injury from these exposures. The study seeks to develop a method for diagnosing brain injuries caused by repeated blasts. It is suitable for active-duty Navy SEALs either early in their career (0-2 years) or with 10-15 years of experience. As a Phase 2 trial, this research measures the effectiveness of the diagnostic method in an initial, smaller group of participants, providing a valuable opportunity to advance brain injury diagnosis.

Do I need to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators to get a clear answer.

What prior data suggests that this diagnostic testing protocol is safe for detecting repeated blast brain injury?

Research has shown that PBR28 TSPO PET is under study for its ability to detect brain inflammation, which is crucial for understanding brain injuries, such as those from repeated blasts. Studies have found that TSPO ligands, like PBR28, can help identify changes in the brain.

Regarding safety, PBR28 has been used in PET scans to observe brain inflammation without major safety concerns. However, a known issue exists with how PBR28 binds in different individuals, affecting results due to genetic differences, though this does not indicate safety problems.

Since this treatment is in a Phase 2 trial, it has already passed initial safety tests in earlier stages, indicating it is generally well-tolerated in humans. For those considering joining the trial, these findings suggest the treatment has a solid safety profile so far, with no major risks reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the PBR28 TSPO PET treatment because it offers a novel approach to understanding traumatic brain injury (TBI) by focusing on brain imaging rather than traditional symptomatic treatments. Unlike standard care options that primarily manage symptoms and recovery, PBR28 TSPO PET targets the brain's microglial activation, providing insights into the brain's inflammatory response. This new mechanism of action could lead to more precise diagnostics and personalized treatment strategies for TBI, potentially transforming how we approach brain injuries in the future.

What evidence suggests that this diagnostic testing protocol is effective for detecting repeated blast brain injury?

Research has shown that PBR28 TSPO PET scans can detect changes in the brain after a traumatic brain injury (TBI). One study found that these scans identify increased activity in microglia, the cells that react to brain injuries. In animals with brain injuries, this method successfully monitored microglial activity, suggesting potential applicability in humans. However, results in other conditions like schizophrenia and viral infections were not significant. Overall, early findings suggest that PBR28 TSPO PET could be useful for identifying brain changes after trauma. Participants in this trial, specifically active-duty United States Navy SEALs, will undergo these scans as part of comprehensive assessments to evaluate brain changes following TBI. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for active-duty Navy SEALs, both early career (0-2 years) and mid-late career (10-15 years), aged between 18 to 50. It's open to all male SEALs of any race or ethnicity.

Inclusion Criteria

I am an active-duty Navy SEAL.

I am a male.

I am a SEAL with either 0-2 or 10-15 years of experience.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo comprehensive assessments including brain scans, blood tests, and evaluations of cognitive performance, psychological health, and physical symptoms at Massachusetts General Hospital

1 day

1 visit (in-person)

Interim Assessments

Brief assessments conducted every 3 months via phone or video teleconference to monitor participants' health and symptoms

1 hour per session

4 visits (virtual)

1-Year Follow-up

Participants return to Massachusetts General Hospital for follow-up assessments including brain scans, blood tests, and evaluations of cognitive performance, psychological health, and physical symptoms

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the main assessments

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PBR28 TSPO PET

Trial Overview The study is testing a diagnostic protocol using PBR28 TSPO PET scans over four years to see if repeated blast exposure impacts brain health in Navy SEALs.

How Is the Trial Designed?

Group I: Active-duty United States Navy SEALs Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Uniformed Services University of the Health Sciences

Collaborator

Trials

130

Recruited

91,100+

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

Navy SEAL Foundation

Collaborator

Trials

1

Recruited

90+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01547780

Translocator Protein and Inflammation After Traumatic ... In this exploratory study to investigate the ability of PBR28 PET to detect increases in TSPO, the primary goal will be to measure the magnitude and variance of ...

2. nature.com nature.com/articles/s41598-023-43245-0

PET imaging of microglia using PBR28suv determines ... This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8172335/

PET Imaging of Peripheral Benzodiazepine Receptor ... Our results demonstrate that 11C-PBR28 PET can quantitatively detect enahanced microglial activation followingbrain injury in vivo in a rodent model of TBI.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0889159123002167

TSPO PET brain inflammation imaging: A transdiagnostic ... Main outcomes for systemic immunological disorders, viral infections, substance use disorders, schizophrenia and traumatic brain injury were not significant. We ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/54/supplement_2/1740

Synthesis and evaluation of a novel TSPO radiotracer [18F]FM ... In blocking studies, [18F]FM-PBR28 exhibited the high specific and selective binding for TSPO in the traumatic brain injury. [18F]FM-PBR28 was shown to be ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7226777/

Diagnostic and Therapeutic Potential of TSPO Studies ... TSPO ligands of different molecular structures and properties can ameliorate various brain diseases, injuries, and disorders.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2211383520306894

Recent developments on PET radiotracers for TSPO and ... In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and ...

8. nature.com nature.com/articles/s41598-021-03416-3

From positron emission tomography to cell analysis of the ... In this study, we evaluated the use of the 18-kDa translocator protein (TSPO) in positron emission tomography (PET) and cellular analysis to monitor microglial ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5487478/

Microglial Activation in Traumatic Brain Injury - PubMed Central An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J. Cereb. Blood Flow Metab. 32, 1 ...