Efficacy of Methotrexate in Myasthenia Gravis

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Methotrexate

Placebo

About this trial

This is an interventional treatment trial for Myasthenia Gravis focused on measuring myasthenia gravis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Phoenix Neurological Associates
University of California, San Francisco
University of California-Irvine
Forbes Norris MDA/ALS Research Center
University of Florida, Health Science Center Jacksonville
University of Iowa Hospitals and Clinics
University of Kansas Medical Center
Massachusetts General Hospitals
University of North Carolina
Ohio State University
Penn State College of Medicine, The Milton S. Hershey Medical Center
University of Texas Southwestern Medical Center
The Nerve and Muscle Center of Texas
University Health Sciences Center, San Antonio
University of Virginia
University of Toronto

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1

2

Arm Description

Methotrexate

Placebo

Outcomes

Primary Outcome Measures

Total Prednisone Dose Area Under the Curve

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.

Secondary Outcome Measures

Average Prednisone Daily Dose (mg/Day)

Participants were asked to fill out the amount of prednisone they took every day on a paper diary.

Quantitative Myasthenia Gravis (QMG) Score

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

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

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

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

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.

Full Information

NCT ID

NCT00814138

First Posted

December 23, 2008

Last Updated

April 26, 2016

Sponsor

University of Kansas Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT00814138

Brief Title

Efficacy of Methotrexate in Myasthenia Gravis

Official Title

Phase II Trial of Methotrexate in Myasthenia Gravis

Study Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Completed

Study Start Date

April 2009 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Kansas Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myasthenia Gravis

Keywords

myasthenia gravis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1

Arm Type

Active Comparator

Arm Description

Methotrexate

Arm Title

2

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Methotrexate

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

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Weekly

Primary Outcome Measure Information:

Title

Total Prednisone Dose Area Under the Curve

Description

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.

Time Frame

9 months

Secondary Outcome Measure Information:

Title

Average Prednisone Daily Dose (mg/Day)

Description

Participants were asked to fill out the amount of prednisone they took every day on a paper diary.

Time Frame

Total length of time daily dose information was collected, i.e. 9 months.

Title

Quantitative Myasthenia Gravis (QMG) Score

Description

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.

Time Frame