Oxaloacetate in Myasthenia Gravis

Phase 1

• Conditions: Myasthenia Gravis
• Interventions: Drug: Oxaloacetate; Drug: Placebo

• Registration Number: NCT04965987
• Lead Sponsor: University of Kansas Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-10
• Status Verified: 2021-07
• Study First Submitted QC: 2021-07-07
• Last Update Submitted: 2021-07-07
• Study First Posted: 2021-07-16
• Last Update Posted: 2021-07-16
• Study Start: 2021-10
• Primary Completion: 2023-04
• Study Completion: 2023-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Patients 18 and older.
2. 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).
3. Patient's signs and symptoms should not be better explained by another disease process.
4. Patients must be willing to complete the study and return for follow-up visits.
5. 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.
6. 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.
7. Patients can be on prednisone as long as there has been no dose change for 30 days.
8. No planned changes in MG medications during the study

Exclusion Criteria

1. MGFA grade V within 6 months of screening.
2. A history of chronic degenerative, severe psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue.
3. Other major chronic or debilitating illnesses within six months prior to study entry.
4. 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).
5. Thymectomy in the previous three months.
6. History of severe reactions to OAA
7. Participation in a research study within the last 3 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Oxaloacetate	Oxaloacetate	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 1000mg OAA BID for 8 weeks.
Placebo	Placebo	Subjects will take 1000mg Placebo BID for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Safety (Frequency and Severity of Adverse Events)	At weeks 2, 4, 6, 8, 10, and 12	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.

Secondary Outcome Measures

Name	Time	Method
Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Score	Change from Week 4 to Week 8	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.
Quantitative Myasthenia Gravis (QMG) Score	Change from Week 4 to Week 8	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.

Trial Locations

Locations (1)

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States