Quantitative Assessment of Radiation-induced Neuroinflammation - A Proof of Principle Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- SUVr
研究概览
简要总结
QARIN 1 is a study of [18F]DPA-714 Translocation Protein (TSPO) Positron Emission Tomography (PET) for longitudinal, quantitative assessment of brain neuroinflammation following whole brain radiation therapy. This TSPO PET, uses a radioactive tracer. An optional MRI (magnetic resonance imaging) will also be performed to monitor brain microstructure damages induced by neuroinflammation.
Primary Objectives
- Assessment of temporal and regional variability of uptake of translocator protein (TSPO) positron emission tomography (PET) tracer.
- Regional variability will be assessed in medial temporal lobe, frontal lobe, and in white matter
- Temporal variability will be assessed by scanning each subject four-times: at baseline (before or within 2 weeks of start of radiation therapy), before start of chemotherapy, at 1 year from the initiation of the radiation therapy, and at 1.5-2 years from the initiation of the radiation therapy
- Correlation of radiation dose in specific brain regions with radiation induced neuroinflammation as measured by uptake of TSPO PET tracer.
Exploratory Objectives
- Assessment of radiation-induced brain microstructure injuries (RIBMI) in specific brain regions (medial temporal lobe, frontal lobe, and in white matter) using advanced magnetic resonance imaging (MRI) techniques.
- Association of radiation dose with MRI measures of RIBMI in these specific brain regions.
- Association of PET measures of RIN with MRI measures of RIBMI.
- Association of PET measure of RIN and MRI measures of RIBMI in specific regions of interest (ROI) with specific domain of neuro-cognition. For example, to investigate whether PET measure of RIN and MRI measures of RIBMI in hippocampal ROI have strongest association with episodic memory; whether frontal lobe cortical ROI are associated with attention and executive function.
- Association of a novel MRI based technique for assessment of RIN with TSPO PET.
- Association of the PET and MRI measure of neuroinflammation within 2- years of completion of radiation with delayed cognitive outcome that will be measured at 3, 4 and 5 years from the completion of radiation
详细描述
The participant will have 4 PET scans using a novel PET tracer that will help the investigators to quantify when and where in brain neuroinflammation happens following radiation therapy. The participant will receive the first PET scan either before your first dose of radiation therapy or within 2 weeks of the start of radiation therapy. The second PET scan will be obtained before starting chemotherapy. The third scan will be after 1 year of treatment.The final scan will be 1 and a half to 2 years after the start of treatment.The scan process will begin an hour or so after the participant has been given tracer by injection. The entire PET scan process lasts about 2 hours.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 39 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is at least 8 years of age
- •Participants with histologically confirmed medulloblastoma and are scheduled to receive 36 Gy craniospinal irradiation
- •Participant and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
- •Subjects have either have high-affinity or mixed-affinity TSPO binding sites as determined by the single-nucleotide polymorphism (SNP) rs6971 in the TSPO gene.
排除标准
- •Participants with a large pseudomeningocele (>4 cm in size) at the surgical site, complications from ventricular access (evidenced by hemorrhage and/or enhancement along the catheter), large subdural effusion in the supra-tentorial compartment (>1 cm in the maximum transverse dimension). All of these are expected to induce inflammation.
- •Female participants of childbearing age must not be lactating due to theoretical potential harm to the infant from exposure to radiation.
- •Subjects with low-affinity TSPO binding sites as determined by the single-nucleotide polymorphism (SNP) rs6971 in the TSPO gene.
- •Pregnant subjects.
- •Patients needing sedation for the PET scans or optional MRI scans.
- •Participants with a diagnosis of recurrent medulloblastoma.
研究组 & 干预措施
Participants
Participants who meet the eligibility criteria in the study will receive Translocation Protein (TSPO) Positron Emission Tomography (PET) for longitudinal, quantitative assessment of brain neuroinflammation following whole brain radiation therapy.
干预措施: [18F]DPA714 (Drug)
结局指标
主要结局
SUVr
时间窗: follow up 3: up to 2 years after radiation therapy
SUVr values for dorsolateral prefrontal cortex comparing baseline vs. follow up 3.
SUVr
时间窗: follow up 1: up to 13 weeks after radiation therapy
SUVr values for dorsolateral prefrontal cortex comparing baseline vs. follow up 1
SUVr
时间窗: follow up 1 : up to 13 weeks after radiation therapy
SUVr values for medial prefrontal cortex comparing baseline vs. follow up 1
SUVr
时间窗: follow up 2: up to 53 weeks after radiation therapy
SUVr values for dorsolateral prefrontal cortex comparing baseline vs. follow up 2.
次要结局
未报告次要终点