Efficacy of Methotrexate in Myasthenia Gravis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Richard Barohn, MD, University of Kansas
ClinicalTrials.gov Identifier:
NCT00814138
First received: December 23, 2008
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Myasthenia Gravis
Drug: Methotrexate
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Trial of Methotrexate in Myasthenia Gravis

Resource links provided by NLM:


Further study details as provided by University of Kansas:

Primary Outcome Measures:
  • Total prednisone dose [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Quantitative Myasthenia Gravis score [ Time Frame: baseline, monthly for 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: April 2009
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Methotrexate
Drug: 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
Placebo Comparator: 2
Placebo
Other: Placebo
Weekly

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00814138

Locations
United States, Arizona
Phoenix Neurological Associates
Phoenix, Arizona, United States, 85018
United States, California
University of California, San Francisco
Fresno, California, United States, 93701
University of California-Irvine
Irvine, California, United States, 92697
Forbes Norris MDA/ALS Research Center
San Francisco, California, United States, 94115
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Massachusetts General Hospitals
Boston, Massachusetts, United States, 02114
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Penn State College of Medicine, The Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
The Nerve and Muscle Center of Texas
Houston, Texas, United States, 77030
University Health Sciences Center, San Antonio
San Antonio, Texas, United States, 78229
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Canada, Ontario
University of Toronto
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University of Kansas
Investigators
Principal Investigator: Richard Barohn, MD University of Kansas
  More Information

No publications provided

Responsible Party: Richard Barohn, MD, Gertrude and Dewey Zeigler Professor of Neurology, Chairman Deptartment of Neurology, University of Kansas
ClinicalTrials.gov Identifier: NCT00814138     History of Changes
Other Study ID Numbers: 11552, FDA OOPD 003538
Study First Received: December 23, 2008
Last Updated: February 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Kansas:
myasthenia gravis

Additional relevant MeSH terms:
Myasthenia Gravis
Muscle Weakness
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes
Signs and Symptoms
Autoimmune Diseases of the Nervous System
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 18, 2014