Efficacy of Methotrexate in Myasthenia Gravis
Condition: Myasthenia Gravis
MeSH terms: Myasthenia Gravis; Muscle Weakness
Intervention: Methotrexate; Placebo
Intervention description: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study; Weekly
Intervention MeSH terms: Methotrexate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: myasthenia gravis

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.