Phase II Trial of Methotrexate in Myasthenia Gravis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 16
- 主要终点
- Total Prednisone Dose Area Under the Curve
研究概览
简要总结
Myasthenia gravis is a rare neuromuscular disorder characterized by weakness and fatigability of ocular, bulbar, and extremity musculature. The specific aim of this study is to determine if oral methotrexate is an effective therapy for myasthenia gravis (MG) patients who are prednisone dependent. Patients will be randomized to receive either methotrexate or placebo and those who are entered onto this trial will have symptoms and signs of the disease while on prednisone therapy. The hypothesis is that adding methotrexate therapy in these patients will improve the MG manifestations so that the prednisone dose can be reduced and clinical measures of MG severity will improve.
Funding Source - FDA OOPD
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have MGFA MG grades 2, 3, or 4 generalized myasthenia gravis, according to the MGFA classification system
- •Elevated acetylcholine receptor antibody (AChR-Ab) titer.
- •Patient's signs and symptoms should not be better explained by another disease process.
- •Prednisone dose of at least 10 mg/day (or the equivalent in alternate days) and the subject must be on a stable dose of prednisone for 30 days prior to the screening visit.
排除标准
- •A history of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue.
- •Other major chronic or debilitating illnesses within six months prior to study entry.
- •Female patients who are premenopausal and are: (a) pregnant on the basis of a serum pregnancy test, (b) breast-feeding, or (c) not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures).
- •Altered levels of consciousness, dementia, or abnormal mental status.
- •Evidence of thymoma on chest CT or MRI. Such a finding could require immediate thymectomy and would preclude entry into the study.
- •Thymectomy in the previous three months.
- •Patients who have been medicated with azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, IVIg, or other immunosuppressive drugs within the last 60 days.
- •Chest X-ray with evidence of tumor, infection, or interstitial lung disease.
- •Clinical history of chronic or recurrent infections.
- •Daily use of non-steroidal anti-inflammatory drugs (NSAIDs).
- •History of renal or hepatic insufficiency or liver enzymes greater than the upper limit of normal.
- •History of bone marrow hypoplasia, leucopenia, thrombocytopenia, significant anemia, clinical or laboratory evidence of immunodeficiency syndromes.
- •Forced Vital Capacity (FVC) <50% of predicted.
- •MG Grade 1 (ocular only) or 5 (crisis, requiring ventilator).
- •Prior use of methotrexate for any condition.
研究组 & 干预措施
1
Methotrexate
干预措施: Methotrexate (Drug)
2
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Total Prednisone Dose Area Under the Curve
时间窗: 9 months
The primary outcome measure was the nine-month prednisone area under the dose-time curve (AUDTC, months 4-12). The AUDTC was chosen because it accounted for changes in the prednisone dose that could occur frequently during a month.
次要结局
- Average Prednisone Daily Dose (mg/Day)(Total length of time daily dose information was collected, i.e. 9 months.)
- Quantitative Myasthenia Gravis (QMG) Score(Change from Baseline to Month 12)
- MGQOL 12 Month Change(Change from Baseline to Month 12)
- MG-ADL 12 Month Change(Change from Baseline to Month 12)
- Manual Muscle Testing 12 Month Change(Change from Baseline to Month 12)
- MG Composite Change Over 12 Months(Change from Baseline to Month 12)
研究者
Richard Barohn, MD
Gertrude and Dewey Zeigler Professor of Neurology, Chairman Deptartment of Neurology
University of Kansas Medical Center