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Oxaloacetate in Myasthenia Gravis

Primary Purpose

Myasthenia Gravis

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Oxaloacetate
Placebo
Sponsored by
University of Kansas Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myasthenia Gravis

Eligibility Criteria

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

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

Sites / Locations

  • University of Kansas Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Oxaloacetate

Placebo

Arm Description

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.

Subjects will take either 500mg BID, 1000mg BID, or 2000mg BID each day for 4 weeks, depending on which cohort they are assigned to.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
June 10, 2021
Last Updated
July 7, 2021
Sponsor
University of Kansas Medical Center
Collaborators
Terra Biological LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04965987
Brief Title
Oxaloacetate in Myasthenia Gravis
Official Title
A Phase I, Double-Blind, Pilot Study of Oxaloacetate in Myasthenia Gravis
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Unknown status
Study Start Date
October 2021 (Anticipated)
Primary Completion Date
April 2023 (Anticipated)
Study Completion Date
April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Kansas Medical Center
Collaborators
Terra Biological LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Non-Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oxaloacetate
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will take either 500mg BID, 1000mg BID, or 2000mg BID each day for 4 weeks, depending on which cohort they are assigned to.
Intervention Type
Drug
Intervention Name(s)
Oxaloacetate
Other Intervention Name(s)
CRONaxal
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Safety (Frequency and Severity of Adverse Events)
Description
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.
Time Frame
At weeks 2, 4, 6, 8, 10, and 12
Secondary Outcome Measure Information:
Title
Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Score
Description
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.
Time Frame
Change from Week 4 to Week 8
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
Change from Week 4 to Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrew J Heim
Phone
9139459926
Email
aheim2@kumc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mazen Dimachkie, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew J Heim
Phone
913-945-9926

12. IPD Sharing Statement

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Oxaloacetate in Myasthenia Gravis

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