Magnetic Resonance Spectroscopy (MRS) to Determine Neuroinflammation and Oxidative Stress in MPS I
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
- Brain Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS)
研究概览
简要总结
Neuroinflammation and oxidative stress have been shown to be present in persons with mucopolysaccharidosis type I (MPS I), but their effect on disease severity and disease progression is unknown. The investigator intends to employ brain magnetic resonance spectroscopy (MRS), a non-invasive technique, along with analysis of neuroinflammation and oxidative stress biomarkers in the blood, to measure and determine the level of oxidative stress and neuroinflammation, and their impact on clinical variability in MPS I patients.
详细描述
Persons with MPS I have a wide range of clinical manifestations including central nervous system (CNS) impairment. The role of neuroinflammation and oxidative stress is one avenue of investigation which may clarify the broad neurological impairment in MPS I. Finding biomarkers that accurately describe the underlying and ongoing brain pathology is a key not only to understanding the disease, but also to understanding the possibility of new therapeutic approaches for MPS I patients.
The investigator will compare patients with Hurler syndrome, and Hurler-Scheie or Scheie syndrome, with healthy controls. There will be 10 participants in each group, resulting in a total of 30 participants. Within the Hurler-Scheie or Scheie syndrome group, the investigator will examine the association of clinical severity with the proposed measures. These findings might help determine whether hematopoietic cell transplantation (HCT), which is the treatment for Hurler syndrome patients, results in decreased oxidative stress and neuroinflammation as compared to Hurler-Scheie or Scheie syndrome patients, who are treated by enzyme replacement therapy (ERT). Additionally, these findings might help determine whether therapies directed at reducing neuroinflammation and oxidative stress in MPS I could enhance neurological outcomes.
Study hypothesis: neuroinflammation and oxidative stress are present in MPS I subjects and are reflective of disease severity.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •MPS I participants must meet the following:
- •Diagnosis of Hurler syndrome, OR Hurler-Scheie syndrome, OR Scheie syndrome
- •6 years of age or older at time of screening
- •Healthy control participants must meet all of the following:
- •Absence of neurological disorder
- •6 years of age or older at time of screening
排除标准
- •Persons who have any of the following will not be enrolled in this study:
- •Any surgically implanted pacemaker
- •Any indwelling electronic device, including programmable shunts
- •Orthodontic braces, unless non-metallic
- •Other implanted metal in the body other than titanium
- •An inability or unwillingness to complete an MRI/MRS because of low cognitive function or behavioral dysregulation
结局指标
主要结局
Brain Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS)
时间窗: 1 day -Single encounter during an appointment which is set at time of study enrollment.
In a single session, each participant will undergo unsedated brain magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS) to determine the presence and extent of any brain neuroinflammation. These data will be acquired on the 7-Tesla Siemens Prisma scanner at the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota in Minneapolis.
次要结局
- Presence and Level of Interleukin 1 beta (IL1β)(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of Interleukin 2 (IL2)(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of Regulated and Normal T cell Expressed and Secreted (RANTES)(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of Tumor Necrosis Factor Alpha (TNF-α)(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of Neuroinflammatory Biomarker MIP-1alpha(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of Interferon-gamma (IFN-γ)(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Levels of Thiobarbituric Acid Reactive Substances (TBARS)(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of Interleukin 8 (IL8)(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Determination of Blood Glutathione Redox Ratio(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of Superoxide Dismutase (SOD)(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of Total Glutathione(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of 4-hydroxynonenal (4-HNE)(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of 8-isoprostane(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)
- Presence and Level of Catalase(1 day -Single blood draw performed at the same time as the single neuroimaging encounter.)