Efficacy of Methotrexate in Myasthenia Gravis

NCT ID: NCT00814138

Last Updated: 2016-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2014-01-31

Brief 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

Conditions

Myasthenia Gravis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Methotrexate

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study

2

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Weekly

Interventions

Methotrexate

10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study

Intervention Type: DRUG

Placebo

Weekly

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Kansas Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Richard Barohn, MD

Gertrude and Dewey Zeigler Professor of Neurology, Chairman Deptartment of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard Barohn, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Locations

Phoenix Neurological Associates

Phoenix, Arizona, United States

University of California, San Francisco

Fresno, California, United States

University of California-Irvine

Irvine, California, United States

Forbes Norris MDA/ALS Research Center

San Francisco, California, United States

University of Florida, Health Science Center Jacksonville

Jacksonville, Florida, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Massachusetts General Hospitals

Boston, Massachusetts, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

Penn State College of Medicine, The Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

The Nerve and Muscle Center of Texas

Houston, Texas, United States

University Health Sciences Center, San Antonio

San Antonio, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

University of Toronto

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

FDA OOPD 003538

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

11552

Identifier Type: -

Identifier Source: org_study_id