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Trial record 1 of 3 for:    Methotrexate | Myasthenia Gravis
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Efficacy of Methotrexate in Myasthenia Gravis

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ClinicalTrials.gov Identifier: NCT00814138
Recruitment Status : Completed
First Posted : December 24, 2008
Results First Posted : December 23, 2015
Last Update Posted : May 26, 2016
Sponsor:
Information provided by (Responsible Party):
Richard Barohn, MD, University of Kansas Medical Center

Tracking Information
First Submitted Date  ICMJE December 23, 2008
First Posted Date  ICMJE December 24, 2008
Results First Submitted Date  ICMJE July 23, 2015
Results First Posted Date  ICMJE December 23, 2015
Last Update Posted Date May 26, 2016
Study Start Date  ICMJE April 2009
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2015)
Total Prednisone Dose Area Under the Curve [ Time Frame: 9 months ]
The primary outcome measure was the nine-month prednisone area under the dose-time curve (AUDTC, months 4-12). The AUDTC was chosen because it accounted for changes in the prednisone dose that could occur frequently during a month.
Original Primary Outcome Measures  ICMJE
 (submitted: December 23, 2008)
Total prednisone dose [ Time Frame: 9 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2015)
  • Average Prednisone Daily Dose (mg/Day) [ Time Frame: Total length of time daily dose information was collected, i.e. 9 months. ]
    Participants were asked to fill out the amount of prednisone they took every day on a paper diary.
  • Quantitative Myasthenia Gravis (QMG) Score [ Time Frame: Change from Baseline to Month 12 ]
    The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. The scale is from 0 - 3 for each item, with 0 meaning normal and 3 is severe. Total score can range from 0 to 39.
  • Manual Muscle Testing 12 Month Change [ Time Frame: Change from Baseline to Month 12 ]
    This measurement was developed to measure the strength of muscle groups in the face, neck, arms and legs. Measurement is made by grading the amount of weakness. Participants are graded as having normal, mild (25%) weakness, moderate (50%) weakness or severe (75%) weakness and 4 = paralyzed/unable to do. Normal would receive a score of 0, mild would receive a score of 1, moderate would receive a score of 2, severe would receive a score of 3 and unable to perform would receive a score of 4. Range would be from 0 (no weakness) to 76 (complete paralysis).
  • MGQOL 12 Month Change [ Time Frame: Change from Baseline to Month 12 ]
    This test is a 15 item patient-reported scale indicating how myasthenia gravis affects the quality of life. Each item is graded as how true each statement has been over the past 7 days. The scale is 0=Not at all, 1= a little bit, 2= somewhat, 3= quite a bit and 4= very much. The numbers are then added to produce a total score. The MGQOL score would range from 0 (no MG symptoms that affected their quality of life) to a score of 60 (MG symptoms affected they quality of life very much).
  • MG-ADL 12 Month Change [ Time Frame: Change from Baseline to Month 12 ]
    The MG-ADL is an 8 item scale developed to assess myasthenia gravis symptoms. Score will range from 0 (normal - no MG symptoms) to 24 (severe MG symptoms)
  • MG Composite Change Over 12 Months [ Time Frame: Change from Baseline to Month 12 ]
    This scale is composed of components of the QMG, MG-ADL and the MMT. These components have been shown to be the most responsive in previous clinical trials. Each item in the QMG, MG-ADL and the MMT was weighed (Rasch analysis performed) and then assigned a score. Score would range from 0 (no effects from the myasthenia gravis) to a score of 50. A participant with a score of 50 wwould be in the hospital on a ventilator.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2008)
Quantitative Myasthenia Gravis score [ Time Frame: baseline, monthly for 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Methotrexate in Myasthenia Gravis
Official Title  ICMJE Phase II Trial of Methotrexate in Myasthenia Gravis
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

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Myasthenia Gravis
Intervention  ICMJE
  • 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
  • Other: Placebo
    Weekly
Study Arms  ICMJE
  • Active Comparator: 1
    Methotrexate
    Intervention: Drug: Methotrexate
  • Placebo Comparator: 2
    Placebo
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 23, 2008)
50
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2014
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00814138
Other Study ID Numbers  ICMJE 11552
FDA OOPD 003538 ( Other Grant/Funding Number: RO1FD003538 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Richard Barohn, MD, University of Kansas Medical Center
Study Sponsor  ICMJE University of Kansas Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Richard Barohn, MD University of Kansas Medical Center
PRS Account University of Kansas Medical Center
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP