Pilot Study of Long-Term Effects of Repetitive, Low-Level Blast Exposure (RLLBE) on Special Operations Forces (SOF) Service Members
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Neurofilament Light Chain
研究概览
简要总结
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.
详细描述
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:
- 3 Tesla Connectome MRI to detect structural disruption of brain networks
- 7 Tesla MRI to detect functional disruption of brain networks
- Translocator protein (TSPO) PET - ligand [11C]-PBR28 to detect neuroinflammation
- Tau PET - ligand [18F]-MK6240 to detect tau deposition
- Neurocognitive assessments to detect signs of cognitive/behavioral dysfunction
- Self-report indicators of cognitive/behavioral dysfunction
- 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 25 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Adults aged 25-45 years of age
- •Males, regardless of race or ethnicity
- •Active duty Special Operation Forces
- •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)
- •History of combat exposure during any deployment as measured by endorsement of any item on the Combat Exposure Scale (CES)
排除标准
- •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)
- •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
- •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
- •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)
- •Any cardiac, respiratory, or other medical condition that may affect cerebral metabolism
- •Benzodiazepines other than lorazepam, desmethyldiazepam and oxazepam within past month
- •MRI contraindications
- •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
- •Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions, and any greater than normal potential for cardiac arrest
- •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)
- •> 300 lbs (weight limit of the MRI table)
- •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
- •Any condition which, in the opinion of the Principal Investigator, may cause undue risk to the subject
- •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)
结局指标
主要结局
Neurofilament Light Chain
时间窗: Day 1, after 6-8 hour fasting
measured by serum concentration of neurofilament light chain
Behavioral symptoms
时间窗: Day 2
measured by the Neurobehavioral Symptom Inventory
PET Neuroinflammation
时间窗: Day 1
measured by standardized uptake value ratio of TSPO ligand \[11C\]PBR28
Cognitive Function
时间窗: Day 1
measured by the Trail Making Test
Physical symptoms
时间窗: Day 2
measured by the Neurobehavioral Symptom Inventory
Diffusion MRI structural connectivity
时间窗: Day 1
measured by white matter tractography
fMRI resting state functional connectivity
时间窗: Day 2
measured by default mode network connectivity
PET Tau deposition
时间窗: Day 2
measured by standardized uptake value ratio of \[18F\]MK6240
次要结局
未报告次要终点
研究者
Brian L. Edlow, M.D.
Neurocritical Care Faculty and Associate Professor of Neurology
Massachusetts General Hospital