A Combination Trial of Copaxone Plus Estriol in RRMS

描述（由申请人提供）：已知多发性硬化症（MS）复发率在妊娠期间显著降低。该提案将确定雌三醇（妊娠期主要雌激素）口服治疗与注射用克帕松联合使用时，是否会降低复发缓解型多发性硬化症（RRMS）受试者的复发率。以前，在一项初步研究中，已经证明用口服雌三醇治疗RRMS受试者6个月导致连续脑MRI上钆增强病变的显著减少（Annals of Neurology，2002; 52：421-428），并引起免疫应答的有利转变（Journal of Immunology，2003; 171：6267-6274）。这是一项附加研究，旨在通过治疗更长时间并关注临床结局来扩展这些先前的发现。在一项双盲试验中，将Copaxone注射液加雌三醇药丸（每天8毫克）的组合与Copaxone注射液加安慰剂药丸进行比较。治疗持续时间为两年，主要结局指标为复发率。次要结局将包括残疾指标（MSFC、EDSS、7-24 MS生活质量、改良疲劳影响量表和贝克抑郁量表）和复发（增强病变、新T2病变）和残疾（萎缩、T1孔）的MRI替代生物标志物。还将遵循安全性措施（血液检查和妇科评价）。本研究的总体目标是开发一种用于RRMS的口服治疗药物雌三醇。

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) relapses are known to be significantly decreased during pregnancy. This proposal will establish whether oral treatment with estriol, the major estrogen of pregnancy, induces a decrease in relapses in relapsing remitting multiple sclerosis (RRMS) subjects when used in combination with injectable Copaxone. Previously, in a pilot study, it has been demonstrated that treatment of RRMS subjects with oral estriol for six months resulted in a significant reduction in gadolinium enhancing lesions on serial brain MRIs (Annals of Neurology, 2002; 52:421-428) and caused a favorable shift in immune responses (Journal of Immunology, 2003; 171:6267-6274). This is an add-on study aiming to extend these previous findings by treating longer and focusing on clinical outcomes. The combination of Copaxone injection plus estriol pill (8 mg per day) will be compared to Copaxone injection plus placebo pill in a double blind trial. The duration of treatment will be two years and the primary outcome measure will be relapse rate. Secondary outcomes will include disability measures (MSFC, EDSS, 7-24 MS Quality of Life, Modified Fatigue Impact Scale and Beck Depression Inventory) and MRI surrogate biomarkers for relapses (enhancing lesions, new T2 lesions) and disability (atrophy, T1 holes). Safety measures (blood tests and gynecologic evaluations) will also be followed. The overall goal of this study will be the development of an oral treatment, estriol, for RRMS.