Phase 2
N=50
Efficacy of Methotrexate in Myasthenia Gravis
Myasthenia Gravis
Bottom Line
View on ClinicalTrials.gov: NCT00814138 ↗Enrolled (actual)
50
Serious AEs
6.0%
Results posted
Dec 2015
Primary outcome: Primary: Total Prednisone Dose Area Under the Curve — 2996.6; 3484.7 mg*Months — p=0.26
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Methotrexate (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Kansas Medical Center
- Primary completion
- Jan 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Total Prednisone Dose Area Under the Curve |
2996.6; 3484.7 | 0.26 |
| SECONDARY Average Prednisone Daily Dose (mg/Day) |
12.8; 14.6 | 0.26 |
| SECONDARY Quantitative Myasthenia Gravis (QMG) Score |
-1.4; 0.3 | 0.29 |
| SECONDARY Manual Muscle Testing 12 Month Change |
-5.5; -3.3 | 0.28 |
| SECONDARY MGQOL 12 Month Change |
-4.6; -3.7 | 0.82 |
| SECONDARY MG-ADL 12 Month Change |
-1.2; 0.26 | 0.21 |
| SECONDARY MG Composite Change Over 12 Months |
-4.6; -1.3 | 0.09 |
Summary
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
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT00814138). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.