A Combination Trial of Copaxone Plus Estriol in RRMS

Copaxone 加雌三醇治疗 RRMS 的联合试验

• 批准号: 7088538
• 负责人: RHONDA R VOSKUHL
• 金额: $ 50万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7088538
• 关键词: Anti-Inflammatory Agents; Anti-inflammatory; Atrophic; Beck depression inventory; Biological Markers; Blood Tests; Brain; Cells; Clinical; Copaxone; Data; Development; Disease; Double-Blind Method; Enhancing Lesion; Estriol; Estrogens; Evaluation; Fatigue; Gadolinium; Goals; Gynecologic; Immune; Immune response; Immunology; In Vitro; Injectable; Injection of therapeutic agent; Journals; Lesion; Magnetic Resonance Imaging; Measures; Mediating; Metalloproteases; Multiple Sclerosis; Nerve Degeneration; Neurologic; Neurology; Oral; Outcome; Outcome Measure; Pilot Projects; Placebos; Pregnancy; Quality of life; Rate; Relapse; Relapsing-Remitting Multiple Sclerosis; Safety; Sample Size; Testing; Translating; base; chemokine; cytokine; day; disability; gray matter; in vivo Model; pill; protective effect; treatment duration

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.

描述（由申请人提供）：已知多发性硬化症 (MS) 复发在怀孕期间会显着减少。该提案将确定雌三醇（妊娠的主要雌激素）口服治疗与注射用 Copaxone 联合使用是否会减少复发缓解型多发性硬化症 (RRMS) 受试者的复发率。此前，在一项初步研究中，已经证明，用口服雌三醇治疗 RRMS 受试者六个月可导致连续脑 MRI 上钆增强的病变显着减少（Annals of Neurology，2002；52：421-428），并引起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并关注临床结果来扩展先前的发现。 Copaxone 注射液加雌三醇药丸（每天 8 毫克）的组合将在双盲试验中与 Copaxone 注射液加安慰剂药丸的组合进行比较。治疗持续时间为两年，主要结果指标为复发率。次要结果将包括残疾指标（MSFC、EDSS、7-24 MS 生活质量、改良疲劳影响量表和贝克抑郁量表）以及复发（增强病变、新 T2 病变）和残疾（萎缩、T1 孔）的 MRI 替代生物标志物。还将遵循安全措施（血液测试和妇科评估）。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。