Association of Possible Biomarkers With Disease Activity in Patients Treated With Teriflunomide (Aubagio)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Biomarkers and disease activity in patients treated with Teriflunomide (Aubagio)
研究概览
简要总结
The study is a two-year prospective observational study of patients treated with teriflunomide. The investigators will recruit up to 75 patients at baseline, based on the estimate that approximately 20% of these patients (~ 15 patients) will have evidence of disease activity at the end of the first year of treatment with teriflunomide, as determined by clinical evaluation (relapses) and MRI activity (new T2 hyperintense lesions). The investigators will assess the expression of a putative biomarker signature consisting of toll like receptor 2(TLR2), TLR4 and chemokine receptor 1 (CCR1) on CD4 T-subsets at baseline and at intervals on treatment with teriflunomide to determine whether expression of this biomarker signature on one or more CD4 T-subsets correlates with disease activity.
详细描述
TITLE: Association of possible biomarkers with disease activity in patients treated with teriflunomide (Aubagio ®)
A. BACKGROUND Teriflunomide (Aubagio) is a once-daily oral immunomodulatory DMT for patients with relapsing-remitting MS (RRMS) (1). The objective of the present study is to determine whether a putative biomarker signature predicts disease activity in patients treated with teriflunomide. The investigators previously identified a 130-gene signature associated with immune activation that identified patients with MS that had rapid transition to secondary progressive MS (SPMS). From this signature, the investigators identified three genes (TLR2, TLR4 and CCR1) which had increased protein expression on naïve CD4 T-cells in these patients. The investigators also showed that mRNA for an anti-proliferation factor, termed TOB1, was downregulated in these T-cells in patients with rapid MS progression. The findings suggest, therefore, that naïve CD4 T-cell activation identifies patients with MS having a short RRMS duration (2).
For this proposal, the principal investigator suggests that various molecules involved in T-cell activation may also serve as useful biomarkers to predict treatment responses to teriflunomide.
B. STUDY OBJECTIVES
B1. Study objective and specific aims. The objective is to determine whether the T-cell activation markers that were previously identified will predict disease activity in patients treated with teriflunomide.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Treatment naive patients with relapsing-remitting multiple sclerosis
- •Patients treated previously with one or more previous disease-modifying treatments but with a washout period of at least 4 weeks before starting treatment with teriflunomide.
排除标准
- •Acute infections in the preceding 4 weeks
- •Vaccination in the previous 2 months
- •An active malignancy (except basal cell carcinoma)
- •Pregnant or breastfeeding patients
- •Communication difficulty, i.e. unable to understand the study
- •Vulnerable patients, i.e. unable to provide informed consent or lacking legal freedom, e.g. prisoners
研究组 & 干预措施
Patients with active disease
From the cohort of patients receiving teriflunomide - 1 tablet (14 mg) daily, the investigators will identify patients that have active disease..
干预措施: Teriflunomide (Drug)
Patients with stable disease
From the cohort of patients receiving teriflunomide (as above), the investigators will identify patients that have stable disease.
干预措施: Teriflunomide (Drug)
结局指标
主要结局
Biomarkers and disease activity in patients treated with Teriflunomide (Aubagio)
时间窗: 26 months
Primary outcome measure * Membrane expression of TLR2, TLR4 and CCR1 Percent expression and mean fluorescence intensity in CD4 T-cell subsets in active vs. stable patient groups * TOB1 expression by real-time PCR on CD4 T-cell subsets Number of molecules per µg cDNA * PrimeFLow assay Number of T-cells expressing both mRNA and surface membrane TLR2 Number of T-cells expressing mRNA for TOB1 Number of T-cells expressing mRNA for TOB 1 and surface protein for TLR2
次要结局
未报告次要终点