Trial Outcomes & Findings for Efficacy of Methotrexate in Myasthenia Gravis (NCT NCT00814138)
NCT ID: NCT00814138
Last Updated: 2016-05-26
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
50 participants
Primary outcome timeframe
9 months
Results posted on
2016-05-26
Participant Flow
Participant milestones
| Measure |
1 - Methotrexate (2.5 mg)
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
Placebo: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
25
|
|
Overall Study
COMPLETED
|
24
|
18
|
|
Overall Study
NOT COMPLETED
|
1
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy of Methotrexate in Myasthenia Gravis
Baseline characteristics by cohort
| Measure |
Methotrexate
n=25 Participants
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
n=25 Participants
Placebo: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Age, Continuous
|
66.5 years
n=5 Participants
|
68.6 years
n=7 Participants
|
67.6 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
22 participants
n=5 Participants
|
21 participants
n=7 Participants
|
43 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 9 monthsPopulation: Myasthenia Gravis patients aged 18 and older that were acetylcholine antibody positive with a myasthenia gravis foundation score of Grade II, III or IV.
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.
Outcome measures
| Measure |
Methotrexate
n=25 Participants
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
n=25 Participants
Placebo: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
|
|---|---|---|
|
Total Prednisone Dose Area Under the Curve
|
2996.6 mg*Months
Interval 1495.9 to 4497.3
|
3484.7 mg*Months
Interval 2151.8 to 4817.5
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Methotrexate
n=25 Participants
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
n=25 Participants
Placebo: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
|
|---|---|---|
|
Average Prednisone Daily Dose (mg/Day)
|
12.8 mg/day
Interval 9.1 to 16.5
|
14.6 mg/day
Interval 11.5 to 17.8
|
SECONDARY outcome
Timeframe: Change from Baseline to Month 12The 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.
Outcome measures
| Measure |
Methotrexate
n=25 Participants
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
n=25 Participants
Placebo: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
|
|---|---|---|
|
Quantitative Myasthenia Gravis (QMG) Score
|
-1.4 units on a scale
Interval -2.9 to 0.1
|
0.3 units on a scale
Interval -1.8 to 2.4
|
SECONDARY outcome
Timeframe: Change from Baseline to Month 12This 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).
Outcome measures
| Measure |
Methotrexate
n=25 Participants
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
n=25 Participants
Placebo: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
|
|---|---|---|
|
Manual Muscle Testing 12 Month Change
|
-5.5 units on a scale
Interval -7.4 to -3.8
|
-3.3 units on a scale
Interval -6.6 to 0.1
|
SECONDARY outcome
Timeframe: Change from Baseline to Month 12This 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).
Outcome measures
| Measure |
Methotrexate
n=25 Participants
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
n=25 Participants
Placebo: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
|
|---|---|---|
|
MGQOL 12 Month Change
|
-4.6 units on a scale
Interval -9.1 to -0.1
|
-3.7 units on a scale
Interval -8.4 to 1.0
|
SECONDARY outcome
Timeframe: Change from Baseline to Month 12The 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)
Outcome measures
| Measure |
Methotrexate
n=25 Participants
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
n=25 Participants
Placebo: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
|
|---|---|---|
|
MG-ADL 12 Month Change
|
-1.2 units on a scale
Interval -2.3 to -0.5
|
0.26 units on a scale
Interval -0.9 to 1.5
|
SECONDARY outcome
Timeframe: Change from Baseline to Month 12This 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.
Outcome measures
| Measure |
Methotrexate
n=25 Participants
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
n=25 Participants
Placebo: 10 mg weekly for 2 weeks and then increase to 15mg for 2 weeks and then 20mg weekly until the end of the study
|
|---|---|---|
|
MG Composite Change Over 12 Months
|
-4.6 units on a scale
Interval -6.4 to -2.7
|
-1.3 units on a scale
Interval -3.7 to 1.1
|
Adverse Events
Methotrexate Group - Adverse Events
Serious events: 2 serious events
Other events: 23 other events
Deaths: 0 deaths
Placebo Group - Adverse Events
Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Methotrexate Group - Adverse Events
n=25 participants at risk
Reported the number of adverse events in the group randomized to methotrexate.
|
Placebo Group - Adverse Events
n=25 participants at risk
Reported the number of adverse events in the group randomized to placebo
|
|---|---|---|
|
Nervous system disorders
Stroke
|
0.00%
0/25 • Adverse event data was collected over the 12 months the participants participated in the study.
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Gastrointestinal disorders
Pancreatitis
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected over the 12 months the participants participated in the study.
|
0.00%
0/25 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Blood and lymphatic system disorders
Thrombosis
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected over the 12 months the participants participated in the study.
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/25 • Adverse event data was collected over the 12 months the participants participated in the study.
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected over the 12 months the participants participated in the study.
|
Other adverse events
| Measure |
Methotrexate Group - Adverse Events
n=25 participants at risk
Reported the number of adverse events in the group randomized to methotrexate.
|
Placebo Group - Adverse Events
n=25 participants at risk
Reported the number of adverse events in the group randomized to placebo
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Pain
|
52.0%
13/25 • Number of events 36 • Adverse event data was collected over the 12 months the participants participated in the study.
|
56.0%
14/25 • Number of events 29 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Hepatobiliary disorders
Elevation of liver function tests
|
12.0%
3/25 • Number of events 8 • Adverse event data was collected over the 12 months the participants participated in the study.
|
16.0%
4/25 • Number of events 12 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Infections and infestations
Infection
|
52.0%
13/25 • Number of events 28 • Adverse event data was collected over the 12 months the participants participated in the study.
|
28.0%
7/25 • Number of events 17 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Endocrine disorders
Allergic
|
4.0%
1/25 • Number of events 1 • Adverse event data was collected over the 12 months the participants participated in the study.
|
0.00%
0/25 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Gastrointestinal disorders
Gastrointestinal
|
60.0%
15/25 • Number of events 28 • Adverse event data was collected over the 12 months the participants participated in the study.
|
44.0%
11/25 • Number of events 16 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary
|
36.0%
9/25 • Number of events 13 • Adverse event data was collected over the 12 months the participants participated in the study.
|
28.0%
7/25 • Number of events 12 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Blood and lymphatic system disorders
Edema/bruising
|
24.0%
6/25 • Number of events 9 • Adverse event data was collected over the 12 months the participants participated in the study.
|
28.0%
7/25 • Number of events 11 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Eye disorders
Ophthalomologic
|
20.0%
5/25 • Number of events 5 • Adverse event data was collected over the 12 months the participants participated in the study.
|
16.0%
4/25 • Number of events 7 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Skin and subcutaneous tissue disorders
Dermatological
|
12.0%
3/25 • Number of events 7 • Adverse event data was collected over the 12 months the participants participated in the study.
|
20.0%
5/25 • Number of events 10 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
General disorders
Constitutional/other
|
40.0%
10/25 • Number of events 24 • Adverse event data was collected over the 12 months the participants participated in the study.
|
32.0%
8/25 • Number of events 34 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness/fatigue
|
40.0%
10/25 • Number of events 24 • Adverse event data was collected over the 12 months the participants participated in the study.
|
32.0%
8/25 • Number of events 34 • Adverse event data was collected over the 12 months the participants participated in the study.
|
|
Blood and lymphatic system disorders
Hematologic
|
24.0%
6/25 • Number of events 13 • Adverse event data was collected over the 12 months the participants participated in the study.
|
20.0%
5/25 • Number of events 8 • Adverse event data was collected over the 12 months the participants participated in the study.
|
Additional Information
Richard J. Barohn, MD/ Chairman of Neurology
University of Kansas Medical Center
Phone: 913-588-6094
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place