Clinical trial NCT00814138: Efficacy of Methotrexate in Myasthenia Gravis
Official title: Phase II Trial of Methotrexate in Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthenia Gravis
Keywords: myasthenia gravis
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2008-12-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Total Prednisone Dose Area Under the Curve
timeFrame: 9 months
Secondary outcomes:
measure: Average Prednisone Daily Dose (mg/Day)
timeFrame: Total length of time daily dose information was collected, i.e. 9 months.
measure: Quantitative Myasthenia Gravis (QMG) Score
timeFrame: Change from Baseline to Month 12
measure: Manual Muscle Testing 12 Month Change
timeFrame: Change from Baseline to Month 12
measure: MGQOL 12 Month Change
timeFrame: Change from Baseline to Month 12
measure: MG-ADL 12 Month Change
timeFrame: Change from Baseline to Month 12
measure: MG Composite Change Over 12 Months
timeFrame: Change from Baseline to Month 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Neurological Associates
state: Arizona
city: Fresno
country: United States
facility: University of California, San Francisco
state: California
city: Irvine
country: United States
facility: University of California-Irvine
state: California
city: San Francisco
country: United States
facility: Forbes Norris MDA/ALS Research Center
state: California
city: Jacksonville
country: United States
facility: University of Florida, Health Science Center Jacksonville
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospitals
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Hershey
country: United States
facility: Penn State College of Medicine, The Milton S. Hershey Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The Nerve and Muscle Center of Texas
state: Texas
city: San Antonio
country: United States
facility: University Health Sciences Center, San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
affiliation: University of Kansas Medical Center
name: Richard Barohn, MD
role: PRINCIPAL_INVESTIGATOR
References: