A Combination Trial of Copaxone Plus Estriol in RRMS

描述(由申请人提供)：多发性硬化症(MS)的复发已知在怀孕期间显著减少。这项建议将确定口服雌三醇(妊娠的主要雌激素)是否能减少复发性缓解性多发性硬化症(RRMS)患者的复发，当与可注射的Copaxone联合使用时。此前，在一项初步研究中，已经证明口服雌三醇治疗RRMS受试者6个月可显著减少系列脑部核磁共振成像中Gd增强的病变(Annals of Neuroology，2002；52：421-428)，并引起免疫反应的有利转变(《免疫学杂志》2003；171：6267-6274)。这是一项附加研究，旨在通过延长治疗时间并关注临床结果来扩展这些先前的发现。在一项双盲试验中，将比较联合服用Copaxone注射液加雌三醇丸(每天8毫克)和Copaxone注射液加安慰剂药片。疗程为两年，主要疗效指标为复发率。次要结果将包括残疾测量(MSFC、EDSS、7-24毫秒生活质量、修正的疲劳影响量表和贝克抑郁问卷)和MRI替代生物标志物，用于复发(强化病变、新的T2病变)和残疾(萎缩、T1孔洞)。还将遵循安全措施(验血和妇科评估)。这项研究的总体目标是开发一种治疗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.