Ferumoxytol-enhanced Imaging and Quantitative Susceptibility Mapping in neuroAIDS
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in the proportion of abnormal MRIs
研究概览
简要总结
This project will investigate the ability of a novel MRI contrast agent to identify and quantitate ongoing monocyte/macrophage (M/MΦ)-mediated inflammation in the brains of HIV-infected individuals.
详细描述
HIV-associated neurocognitive disorders (HAND) continue to be prevalent despite effective combination antiretroviral therapy (cART) and have a significant impact on morbidity and quality of life. Monocytes/macrophages (M/MΦ) are believed to play a critical role in the pathogenesis of HAND. Neuroimaging HIV research has not focused on assessing M/MΦ-mediated inflammation in the brain. Currently, no neuroimaging modality exists that can define the extent of active inflammation due to M/MΦ in HAND either as a clinical diagnostic tool or to assist in defining objective improvement in clinical trials addressing HAND. Ferumoxytol is an ultra-small iron oxide MRI contrast agent avidly taken up by circulating M/MΦ. The investigators hypothesize that ferumoxytol-based imaging can identify ongoing inflammation due to perivascular M/MΦ which is believed to represent a key pathologic correlate of HAND.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 40-65 years
- •Plasma HIV RNA < 48 copies/ml (HIV+ subjects only)
- •On stable cART >= 1 year (HIV+ subjects only)
- •Global neuropsychological (NP) score <-0.5 in at least one cognitive domain known to be affected by HIV (neurocognitively impaired subjects only)
- •Documentation of negative HIV infection by an FDA approved test (HIV- subjects only)
排除标准
- •Active substance use
- •History of myocardial infarct or stroke
- •Chronic hepatitis C virus (HCV) infection
- •Uncontrolled major affective disorder, active psychosis, central nervous system disease that affects the brain structure, or other uncontrolled chronic medical condition that in the opinion of the investigator may impact NP testing or the study outcome
- •Psychoactive or other medications which may impact NP testing
- •Factors that preclude MRI
- •Known hypersensitivity to ferumoxytol
- •History of laboratory measurements consistent with an iron overload syndrome
- •Medical conditions that require frequent blood transfusions
- •Taking oral iron supplements
- •Elevated iron levels
- •Any condition, which in the opinion of the investigator, would compromise the subject's ability to participate
- •Multiple drug allergies that may pose a greater risk of anaphylaxis associated with ferumoxytol
- •Pregnant, unwillingness to practice birth control, or breastfeeding
- •Unable to give informed consent
研究组 & 干预措施
HIV+ with neurocognitive disorder
All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion
干预措施: Ferumoxytol (Drug)
HIV+ without neurocognitive impairment
All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion
干预措施: Ferumoxytol (Drug)
HIV- without neurocognitive impairment
All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion
干预措施: Ferumoxytol (Drug)
结局指标
主要结局
Change in the proportion of abnormal MRIs
时间窗: Change from Baseline MRI at 4-6 weeks post-infusion MRI
The proportion of abnormal MRIs will be compared for each group.
次要结局
- Change in quantitative susceptibility mapping (QSM)(Change from Baseline MRI at 4-6 weeks post-infusion MRI)
研究者
Beau Nakamoto
Assistant Professor of Medicine
University of Hawaii