A Combination Trial of Copaxone Plus Estriol in RRMS

描述（由申请人提供）：已知妊娠期间多发性硬化症（MS）复发明显减少。该建议将确定口服雌三醇（妊娠期主要雌激素）与可注射的科帕松联合使用时，是否能减少复发缓解型多发性硬化症（RRMS）患者的复发。先前，在一项初步研究中，已经证明口服雌三醇治疗RRMS受试者6个月后，在一系列脑mri上显示钆增强病变显著减少（Annals of Neurology, 2002; 52:42 -428），并导致免疫反应的有利转变（Journal of Immunology, 2003; 171:6267-6274）。这是一项附加研究，旨在通过延长治疗时间和关注临床结果来扩展先前的研究结果。在双盲试验中，将Copaxone注射液加雌三醇丸（8mg /天）与Copaxone注射液加安慰剂丸进行比较。治疗时间为2年，主要观察指标为复发率。次要结果将包括残疾测量（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MRI替代生物标志物复发（强化病变，新的T2病变）和残疾（萎缩，T1空洞）。还将采取安全措施（血液检查和妇科评估）。本研究的总体目标是开发一种用于治疗RRMS的口服药物雌三醇。

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.