Imaging the Neuroimmune System in PTSD With PET
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Baseline TSPO Availability
研究概览
简要总结
In this study, individuals with and without post-traumatic stress disorder (PTSD) will undergo one positron emission tomography (PET) scan using the radiotracer [11C]PBR28, which binds to the 18kDa translocator protein (TSPO). A subset of individuals who complete the first PET [11C]PBR28 scan will be invited to complete an inflammatory challenge and second PET [11C]PBR28 scan. Approximately 3 hours prior to the second [11C]PBR28 PET scan, lipopolysaccharide (LPS; endotoxin) will be administered to evoke a robust neuroimmune response. Subjects will also undergo behavioral and cognitive testing. Vital signs, subjective response, and peripheral biomarker levels will be assayed periodically throughout the experimental session.
Specific aims: 1) Determine if individuals with PTSD exhibit neuroimmune system disruption relative to well-matched comparators at baseline. 2) Determine if individuals with PTSD exhibit a disrupted neuroimmune response after a classical immune stimulus relative to well-matched comparators. 3) Determine if LPS differentially alters cognitive function, subjective response, or physiological markers in individuals with PTSD compared to well-matched comparators.
Hypothesis: Individuals with PTSD will exhibit a suppressed neuroimmune system at baseline and an attenuated neuroimmune response following LPS challenge, relative to matched trauma controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women, aged 18-55 years
- •Subjects with PTSD will have a primary, current diagnosis of PTSD according to DSM-V criteria (i.e., CAPS-5 ascertained diagnosis)
- •Able to read and write English and to provide voluntary, written informed consent
排除标准
- •Current medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology including COPD, anemia, uncontrolled daily asthma or asthma requiring the use of an inhaler more than 1x/week with an ACT score below
- •[We will not exclude individuals taking SSRIs and TRIs due to high prevalence of use within the PTSD population and due to evidence suggesting no effect of these drug classes on endotoxin response].
- •Past or current neurological disorder or disorders affecting the brain including but not limited to multiple sclerosis, history of stroke, brain tumors, traumatic brain injury with loss of consciousness, seizure disorder
- •Current or regular use of over-the-counter medication that may affect the immune system
- •Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD
- •Contraindications to MRI such as claustrophobia or metal in their body
- •Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population)
研究组 & 干预措施
Post-LPS [11C]PBR28 PET Scan
Subjects will complete a second120-minute [11C]PBR28 PET scan 3-hours after LPS administration (1.0ng/kg; IV)
干预措施: Lipopolysaccharide (Drug)
结局指标
主要结局
Baseline TSPO Availability
时间窗: Before LPS administration (baseline)
Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t\*=30) incorporating the metabolite-corrected arterial input function to yield \[11C\]PBR28 total volumes of distribution (VT) across brain regions.
Post-LPS TSPO Availability
时间窗: 3-hours after LPS administration (1.0 ng/kg; IV)
Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t\*=30) incorporating the metabolite-corrected arterial input function to yield \[11C\]PBR28 total volumes of distribution (VT) across brain regions.
次要结局
- Baseline Visual Learning(Before LPS administration)
- Baseline Visual Attention(Before LPS administration)
- Post-LPS Visual Attention(Approximately ~1-hour after LPS administration)
- Post-LPS Visual Learning(Approximately ~1-hour after LPS administration)
- Baseline Verbal Memory(Before LPS administration)
- Post-LPS Verbal Memory(Approximately ~1-hour after LPS administration)
- Baseline Executive Function(Before LPS administration)
- Post-LPS Executive Function(Approximately ~1-hour after LPS administration)
- Baseline Visual-Motor Processing Speed(Before LPS administration)
- Post-LPS Visual-Motor Processing Speed(Approximately ~1-hour after LPS administration)
- Baseline Social Cognition(Before LPS administration)
- Post-LPS Social Cognition(Approximately ~1-hour after LPS administration)
研究者
Kelly Cosgrove
Associate Professor
Yale University