Effect of Ocrelizumab on Neuroinflammation in Multiple Sclerosis as Measured by 11C-PBR28 MR-PET Imaging of Microglia Activation
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- 11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR)
研究概览
简要总结
Using magnetic resonance-PET (MR-PET) imaging with [11C]PBR28, a second-generation 18kDa translocator protein (TSPO) radiotracer, we have previously demonstrated abnormally high TSPO expression, indicative of microglia activation, across different brain tissue compartments of multiple sclerosis (MS) patients1.
In this study, we propose to study the efficacy of ocrelizumab, a humanized monoclonal antibody that has been shown to decrease neuroinflammation in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (MS) patients.
We will test these effects by studying a cohort of 24 MS patients (12 RRMS, 12 progressive MS). Participants will be studied before (within 3 months prior to initiating treatment) and after treatment with ocrelizumab (~12 month follow up), a therapeutic drug that will be part of their standard medical care. We will use [11C]PBR28 to help determine changes in neuroinflammation.
The purpose of this study is to determine the effects of ocrelizumab treatment on neuroinflammation by analyzing the uptake and distribution of [11C]PBR28 in individuals with multiple sclerosis. The specific aims of the current study are:
- To assess whether treatment with ocrelizumab in subjects with either relapsing-remitting MS or progressive MS is associated with decreased [11C]PBR28 binding in the cortex and white matter (lesions and normal appearing white matter), suggesting reduced neuroinflammation.
- To assess whether changes in neuroinflammation under ocrelizumab treatment, as measured by [11C]PBR28 uptake at 12-month follow up relative to baseline, are associated with changes in structural MR metrics of brain tissue damage including white matter lesion load, cortical atrophy, and demyelination in the cortex and in the normal-appearing white matter as measured by magnetization transfer ratio (MTR).
- To explore whether changes in functional and structural imaging metrics under ocrelizumab are associated with changes in clinical outcome measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •RRMS and/or PMS subtype
- •EDSS between 0 and 7.0
- •Express at least one high-affinity (Ala147) allele of the TSPO receptor for PBR28
- •Initiating Ocrelizumab treatment within the next 3 months
排除标准
- •Hypersensitivity to trial medications
- •History of life-threatening reaction to Ocrelizumab
- •Acute or uncontrolled chronic medical condition
- •Impaired hearing
- •Claustrophobia
- •300 lbs of greater (weight limit of MRI table)
- •Pregnancy or breastfeeding
- •Sensitivity to imaging agents
- •Contraindications to MRI
- •Use of benzodiazepines, topiramate, doxycycline, mynocicline
研究组 & 干预措施
Multiple sclerosis patients
Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy.
干预措施: 11C-PBR28 (Drug)
结局指标
主要结局
11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR)
时间窗: Baseline to 12 month
The primary endpoint is change in mean 11C-PBR28 SUVR in multiple sclerosis patients after 1-year of ocrelizumab therapy in different brain regions.
次要结局
- White Matter (WM) Lesion Volume(Baseline to 12 months)
- Magnetization Transfer Ratio (MTR)(Baseline to 12-month)
- Cortical Thickness(Baseline to 12-month)
研究者
Caterina Mainero
Principal Investigator
Massachusetts General Hospital