Oxaloacetate in Myasthenia Gravis

Study Overview
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Brief Summary
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This is a phase 1 clinical trial studying whether or not oxaloacetate has a positive effect on patients with Myasthenia Gravis. Patients will be assigned to one of three cohorts which will determine the dose of oxaloacetate they will be given. Subjects will take the study drug for 4 weeks and be on placebo for 4 weeks.

Official Title
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A Phase I, Double-Blind, Pilot Study of Oxaloacetate in Myasthenia Gravis

Conditions
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Myasthenia Gravis

Intervention / Treatment
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* Drug: Oxaloacetate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 and older. Patients must have prior or current documentation of MGFA MG grades 2, 3, or 4A generalized MG, according to the MGFA classification system. These grades correspond to mild (2), moderate (3), and severe (4). Patient's signs and symptoms should not be better explained by another disease process. Patients must be willing to complete the study and return for follow-up visits. Patients must be willing to give written informed consent before participating in this study. A copy of the signed consent must be kept in the patient's medical record. Patients can be on the following drugs as long as there has been no dose change for 60 days: azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, tacrolimus, methotrexate, IVIg or other immunosuppressive drugs. Patients can be on prednisone as long as there has been no dose change for 30 days. No planned changes in MG medications during the study Exclusion Criteria: MGFA grade V within 6 months of screening. A history of chronic degenerative, severe 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). Thymectomy in the previous three months. History of severe reactions to OAA Participation in a research study within the last 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxaloacetate<br>Oxaloacetate (OAA) is a four-carbon molecule involved in many metabolic pathways, including gluconeogenesis, citric acid cycle, glyoxylate cycle, urea cycle, and amino acid metabolism. In the glyoxylate and citric acid cycles, oxaloacetate is formed as the result of the catalysis by malate dehydrogenase. Subjects will take either 500mg BID, 1000mg BID, or 2000mg BID each day for 4 weeks, depending on which cohort they are assigned to. | Drug: Oxaloacetate<br>* Oxaloacetate (OAA) is a four-carbon molecule involved in many metabolic pathways, including gluconeogenesis, citric acid cycle, glyoxylate cycle, urea cycle, and amino acid metabolism. In the glyoxylate and citric acid cycles, oxaloacetate is formed as the result of the catalysis by malate dehydrogenase. In this reaction, the hydrogen atoms from malate are transferred to NAD+, forming NADH, H+ and oxaloacetate. Oxaloacetate can be converted to citrate with the addition of acetyl-CoA by the enzyme citrate synthase. Oxaloacetate is a critical component in the production of ATP and must be constantly regenerated in order for the citric acid cycle and the electron transport chain to continue<br>* Other names: CRONaxal;|
| Placebo Comparator: Placebo<br>Subjects will take either 500mg BID, 1000mg BID, or 2000mg BID each day for 4 weeks, depending on which cohort they are assigned to. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Frequency and Severity of Adverse Events) | The primary endpoint of safety will be reported as counts of subjects experiencing adverse events events (including abnormal laboratory results and vital signs). Measures of safety will be reported for the last visit observed for each participant. | At weeks 2, 4, 6, 8, 10, and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Score | Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL): Composite measure of scores from measurement scales. The MG-ADL has a scale of 0 - 24 with 0 being the lowest (no symptoms) and 24 being the highest (most severe symptoms. The MG-ADL is a staff-administered, patient-reported questionnaire that measures 8 commons symptoms of myasthenia gravis and grades them on a scale of 0 - 3. | Change from Week 4 to Week 8 | 
| 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. | Change from Week 4 to Week 8 |