Myasthenia GravisPhase 2NCT00814138
Efficacy of Methotrexate in Myasthenia Gravis
A Phase 2 study testing Methotrexate in people with Myasthenia Gravis, run by University of Kansas Medical Center at 16 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myasthenia Gravis
- What is being tested?
- Methotrexate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 16 sitesin 2 countries
- Study dates
- Apr 2009to Jan 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
16 sites in 2 countries.
16 sites in 2 countries
United States15 sites
Massachusetts General Hospitals
Boston, Massachusetts, 02114
University of North Carolina
Chapel Hill, North Carolina, 27599
University of Virginia
Charlottesville, Virginia, 22908
Ohio State University
Columbus, Ohio, 43210
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of California, San Francisco
Fresno, California, 93701
Penn State College of Medicine, The Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
The Nerve and Muscle Center of Texas
Houston, Texas, 77030
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of California-Irvine
Irvine, California, 92697
University of Florida, Health Science Center Jacksonville
Jacksonville, Florida, 32209
University of Kansas Medical Center
Kansas City, Kansas, 66160
Phoenix Neurological Associates
Phoenix, Arizona, 85018
University Health Sciences Center, San Antonio
San Antonio, Texas, 78229
Forbes Norris MDA/ALS Research Center
San Francisco, California, 94115
About this study
Official title: Phase II Trial of Methotrexate in Myasthenia Gravis
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
- Being tested
- Methotrexate, Placebo
- Keywords
- myasthenia gravis
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
PlaceboOther
Weekly
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Methotrexate Receives: Drug: Methotrexate |
| 2 | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 9 months
Secondary outcomes (6)
Average Prednisone Daily Dose (mg/Day)
Participants were asked to fill out the amount of prednisone they took every day on a paper diary.
Measured: Total length of time daily dose information was collected, i.e. 9 months.
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.
Measured: Change from Baseline to Month 12
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).
Measured: Change from Baseline to Month 12
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).
Measured: Change from Baseline to Month 12
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)
Measured: Change from Baseline to Month 12
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.
Measured: Change from Baseline to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2008 (estimated)
- Study startApr 2009
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myasthenia GravisStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Barohn, MD, University of Kansas Medical Center
- Investigators
- Richard Barohn, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00814138
- Sponsor's protocol ID
- 11552
- Other IDs
- FDA OOPD 003538
- Status last verified
- Apr 2016
- First submitted
- 23 Dec 2008
- Last updated
- 26 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Methotrexate in Myasthenia Gravis
- ClinicalTrials.gov ID
- NCT00814138
- Acronym / sponsor ID
- 11552
- Conditions
- Myasthenia Gravis
- Keywords
- myasthenia gravis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 24 Dec 2008 (estimated)
- Results
- Posted 23 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: MethotrexateMethotrexate |
| 2 | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methotrexate10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study | Drug | 1 |
| PlaceboWeekly | Other | 2 |
Primary outcome
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.
6 secondary outcomes
Average Prednisone Daily Dose (mg/Day)
Time frame: Total length of time daily dose information was collected, i.e. 9 months.
Quantitative Myasthenia Gravis (QMG) Score
Time frame: Change from Baseline to Month 12
Manual Muscle Testing 12 Month Change
Time frame: Change from Baseline to Month 12
MGQOL 12 Month Change
Time frame: Change from Baseline to Month 12
MG-ADL 12 Month Change
Time frame: Change from Baseline to Month 12
MG Composite Change Over 12 Months
Time frame: Change from Baseline to Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Myasthenia Gravis
Active, not recruitingPhase 3
An Extension Study Evaluating 6-week Treatment Cycles of Rozanolixizumab in Pediatric Study Participants With Generalized Myasthenia Gravis
Generalized Myasthenia Gravis
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Rozanolixizumab in Adult Participants With Ocular Myasthenia Gravis
Ocular Myasthenia Gravis
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingPhase 3
A Study to Evaluate The Long-Term Safety And Efficacy of Rozanolixizumab in Adult Participants With Ocular Myasthenia Gravis
Ocular Myasthenia Gravis
Recruiting
Holistic Assessment and Remote Digital MONitoring of mYasthenia Gravis Via MyoSense 360
Myasthenia Gravis, Generalized
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Barohn, MD principal investigator
University of Kansas Medical Center
16 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methotrexate in people with Myasthenia Gravis, run by University of Kansas Medical Center at 16 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Prednisone Dose Area Under the Curve (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2016.