Long-Term Effects of Repetitive, Low-Level Blast Exposure on Special Operations Forces Service Members

Traumatic Brain Injury Clinical Trial

— ReBlast  

Official title:

Pilot Study of Long-Term Effects of Repetitive, Low-Level Blast Exposure (RLLBE) on Special Operations Forces (SOF) Service Members

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05183087
• Other study ID #: 2020P002695
• Status: Completed
• Start date: July 1, 2021
• Est. completion date: February 28, 2023

Study information

• Verified date: April 2023
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a pilot study to identify biomarkers that individually, and in combination, demonstrate the greatest sensitivity to repetitive, low-level blast exposure (RLLBE) neurotrauma in Special Operations Forces (SOF) personnel. The proposed cross-sectional, multimodal study will elucidate the potential effects of long-term RLLBE by comparing biomarkers across subjects.

Description:

The proposal includes a comprehensive battery of assessments characterized by high-field neuroimaging, proteomics, and experimental cognitive and neurobehavioral evaluations, which will be implemented alongside standardized clinical diagnostic tools. The results will inform the design of a larger trial to validate the diagnostic utility of these biomarkers as well as their ability to predict RLLBE-related clinical outcomes. A secondary aim will be to define the underlying mechanisms, risk and resilience factors, and clinical phenotypes associated with RLLBE. Biomarkers assessed over the course of a two-day evaluation will include: 1. 3 Tesla Connectome MRI to detect structural disruption of brain networks 2. 7 Tesla MRI to detect functional disruption of brain networks 3. Translocator protein (TSPO) PET - ligand [11C]-PBR28 to detect neuroinflammation 4. Tau PET - ligand [18F]-MK6240 to detect tau deposition 5. Neurocognitive assessments to detect signs of cognitive/behavioral dysfunction 6. Self-report indicators of cognitive/behavioral dysfunction 7. Blood biomarkers to detect evidence of blast injury using proteomics and metabolomics We hypothesize that a multimodal assessment using Connectome MRI, 7 Tesla MRI, TSPO PET, Tau PET, cognitive/behavioral tests, proteomics and metabolomics will identify biomarkers of RLLBE-related brain injury.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 28, 2023
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 25 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Adults aged 25-45 years of age

2. Males, regardless of race or ethnicity

3. Active duty Special Operation Forces

4. History of combat deployment confirmed by Veterans Affairs (VA) or Department of Defense (DOD) records (defined as: while serving in the U.S. military, individual was deployed to a region of conflict)

5. History of combat exposure during any deployment as measured by endorsement of any item on the Combat Exposure Scale (CES)

Exclusion Criteria:

1. History of moderate or severe traumatic brain injury (TBI) (using the VA/DOD definition: initial Glasgow Coma Scale score < 13, coma duration > ½ hr, post-traumatic amnesia duration > 24 hr, or abnormal structural brain imaging)

2. History of major neurologic disorder such as stroke or spinal cord injury resulting in a significant decrement in functional status or loss of independent living capacity

3. Untreated or unstable severe psychiatric condition (e.g., schizophrenia or bipolar disorder) that is likely to impact study participation or ability to complete study procedures

4. Current severe medical condition (excluding currently diagnosed mild TBI or concussion) that requires long-term treatments (e.g., cancer, diabetes mellitus, human immunodeficiency virus, autoimmune disorders)

5. Any cardiac, respiratory, or other medical condition that may affect cerebral metabolism

6. Benzodiazepines other than lorazepam, desmethyldiazepam and oxazepam within past month

7. MRI contraindications

1. Metal in the body that would make an MRI scan unsafe, such as pacemakers, medication pumps, aneurysm clips, metallic prostheses (including metal pins and rods, heart valves or cochlear implants), shrapnel fragments, permanent eye liner or small metal fragments in the eye

2. Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions, and any greater than normal potential for cardiac arrest

3. Inability to lie supine for up to 2 hours in the MRI scanner, as assessed by physical examination and medical history (e.g., back pain, arthritis)

4. > 300 lbs (weight limit of the MRI table)

8. Prior radiation exposure of = 50 mSv over the past 12 months, in the context of research, as determined by review of DOD medical records (e.g., prior imaging studies) and self-report

9. Any condition which, in the opinion of the Principal Investigator, may cause undue risk to the subject

10. Other: Any condition or characteristic that in the judgment of the Principal Investigator would create a logistical or safety contraindication to enrollment (e.g., shoulder width greater than the bore of the MRI or PET/MRI machines)

Related Conditions & MeSH terms

• Blast Injuries
• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Diagnostic Test:
• 3T Connectome MRI
MRI scan of structural connectivity
• 7 Tesla MRI
MRI scan of functional connectivity
• TSPO PET
PET scan of neuroinflammation
• Tau PET
PET scan of tau deposition
• Cognitive and Behavioral Assessments
Assessments of memory, attention, complex reasoning, mood and other cognitive/behavioral domains
• Blood Biomarkers
Blood-based assessments of proteomic and metabolic biomarkers of brain injury

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diffusion MRI structural connectivity	measured by white matter tractography	Day 1
Primary	fMRI resting state functional connectivity	measured by default mode network connectivity	Day 2
Primary	PET Neuroinflammation	measured by standardized uptake value ratio of TSPO ligand [11C]PBR28	Day 1
Primary	PET Tau deposition	measured by standardized uptake value ratio of [18F]MK6240	Day 2
Primary	Neurofilament Light Chain	measured by serum concentration of neurofilament light chain	Day 1, after 6-8 hour fasting
Primary	Cognitive Function	measured by the Trail Making Test	Day 1
Primary	Behavioral symptoms	measured by the Neurobehavioral Symptom Inventory	Day 2
Primary	Physical symptoms	measured by the Neurobehavioral Symptom Inventory	Day 2