Effect of Natalizumab (Tysabri®) on Remyelination in Patients With Relapsing-remitting Multiple Sclerosis. A Follow-up Voxel-wise Magnetization Transfer Imaging Study.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- To define the effect of Tysabri monotherapy on a voxel-wise basis using magnetization transfer ratio dynamic mapping of the lesions and normal appearing brain tissue in patients with relapsing-remitting multiple sclerosis.
研究概览
简要总结
The primary objective of this study is to define the effect of Tysabri in patients with relapsing-remitting (RR) multiple sclerosis (MS) over 2 years. The investigators will also explore the extent of remyelination in MS patients treated with Tysabri over 2 years.
A secondary objective of this study is to investigate differences in the capacity for remyelination between patients who do or do not respond to Tysabri monotherapy during the same 24 months.
A tertiary objective of this study is to monitor Tysabri effect in MS antiphospholipid antibodies positive and MS antiphospholipid antibodies negative patients and to determine perfusion differences according to the antiphospholipid antibodies positivity status.
详细描述
Magnetization transfer imaging (MTI) is a widely used tool for characterizing the evolution of multiple sclerosis (MS) lesions and normal appearing brain tissue (NABT). As remyelination and demyelination are heterogeneous in each lesion and NABT, techniques such as voxel-wise based MTR dynamic mapping may help predict an individual's clinical course, as well as the effect of treatment, by revealing evidence of myelin repair and neuroprotection.
Natalizumab (Tysabri) showed a robust effect on the decrease of inflammation in phase II and III clinical trials, as evidenced by the decrease in Gd enhancing and T2 lesions and on the decrease of clinical activity as measured by reduction of clinical relapses and progression of disability. The effect of Tysabri on non-conventional measures is only partially known.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
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
- 是
入选标准
- •Patient diagnosed with clinically definite MS according to the Polman criteria
- •Age 18-65
- •Have a RR disease course
- •Have EDSS scores less than or equal to 5.5 {Kurtzke, 1983 #15}
- •Have disease duration less than 20 years
- •Fulfilled the TOUCH enrollment requirements and started on Tysabri monotherapy
- •Signed informed consent
- •None of the exclusion criteria
排除标准
- •Primary progressive, secondary progressive, or progressive relapsing MS. Primary progressive, secondary progressive or progressive relapsing multiple sclerosis.
- •A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to drug start.
- •History of, or abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, and/or other major disease that, in the opinion of the investigator, would preclude the administration of natalizumab for the duration of the study.
- •History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
- •Abnormal blood tests, performed at the screening visit, which exceed any of the limits defined below:
- •ALT/ SGPT, or AST/ SGOT > three times the upper limit of normal (i.e., 3xULN).
- •Total white blood cell (WBC) count <2,300/mm
- •Platelet count <100,000/mm
- •Creatinine > 2xULN.
- •Prothrombin time (PT) > ULN.
- •Any prior treatment during the 2 weeks prior to study screening with agents such as IFN-β, GA, IVIG, or on the following immunosuppressant therapies for less than 3 months: mitoxantrone, cyclophosphamide, cladribine, fludarabine, cyclosporine, azathioprine, methotrexate, Cellcept, etc.
- •History of alcohol or drug abuse within 2 years prior to randomization.
- •Female subjects who are not postmenopausal for at least 1 year, surgically sterile, or willing to practice effective contraception (as defined by the investigator) during the study. The rhythm method is not to be used as the sole method of contraception.
- •Nursing mothers, pregnant women, and women planning to become pregnant while on study.
- •Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol.
- •Any other reasons that, in the opinion of the Investigator, indicate that the subject is unsuitable for enrollment into this study.
研究组 & 干预措施
1
63 patients with relapsing-remitting Multiple Sclerosis who are enrolled in the TOUCH program and have been taking Tysabri monotherapy for 2 years.
干预措施: Tysabri (Drug)
结局指标
主要结局
To define the effect of Tysabri monotherapy on a voxel-wise basis using magnetization transfer ratio dynamic mapping of the lesions and normal appearing brain tissue in patients with relapsing-remitting multiple sclerosis.
时间窗: 2 years
次要结局
- To investigate differences in the capacity for remyelination measured by MTR between patients who do or do not respond to Tysabri monotherapy.(2 years)
研究者
Robert Zivadinov, MD, PhD
Professor of Neurology
University at Buffalo