Oxaloacetate for Myasthenia Gravis

Overseen By Andrew J Heim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Kansas Medical Center

Disqualifiers: Chronic degenerative, Severe psychiatric, Neurologic, others

Compensation: Varies

Number of Visits: 12

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether oxaloacetate, a compound under investigation for its potential therapeutic effects, can aid individuals with Myasthenia Gravis (MG), a condition causing muscle weakness. Participants will receive varying doses of oxaloacetate or a placebo to assess symptom improvement. Eligible patients must have a diagnosis of moderate to severe MG that impacts daily activities. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

You can continue taking your current medications as long as there have been no dose changes recently: 60 days for most immunosuppressive drugs and 30 days for prednisone. No changes in your Myasthenia Gravis medications are planned during the study.

Is there any evidence suggesting that oxaloacetate is likely to be safe for humans?

Research has shown that oxaloacetate is being tested for safety in treating Myasthenia Gravis. This phase 1 trial aims to assess how well people tolerate the treatment. Early trials like this help researchers determine if the drug is safe for humans.

While there isn't specific safety information from past studies on oxaloacetate for this condition, phase 1 trials typically begin with small doses to monitor for side effects. These trials are designed to be cautious and closely monitor participants.

Oxaloacetate plays a role in many body functions, prompting researchers to explore its potential benefits for Myasthenia Gravis. However, at this stage, the primary goal is to ensure it does not cause harm before evaluating its effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Myasthenia Gravis?

Researchers are excited about oxaloacetate for myasthenia gravis because it represents a novel approach compared to the standard treatments like acetylcholinesterase inhibitors and immunosuppressants. Unlike these treatments, which primarily focus on increasing communication between nerves and muscles or dampening the immune system, oxaloacetate is a natural metabolic compound involved in critical energy-producing pathways. This new angle targets metabolic processes, potentially offering a unique way to manage symptoms or enhance energy production in muscle cells. By tapping into these metabolic pathways, oxaloacetate may provide an innovative alternative that complements or offers an advantage over existing therapies.

What evidence suggests that oxaloacetate might be an effective treatment for Myasthenia Gravis?

Research has shown that oxaloacetate might help with muscle weakness. Studies have found that it can reduce tiredness in people with Chronic Fatigue Syndrome and Long COVID. This trial will evaluate oxaloacetate for its potential benefits in Myasthenia Gravis, a condition that causes muscle weakness. Participants will receive either oxaloacetate or a placebo. Oxaloacetate is a natural substance that helps produce energy in the body, which might explain its ability to improve tiredness and weakness. Although direct proof for Myasthenia Gravis is lacking, the mechanism of oxaloacetate suggests it could be helpful. ^{1 2 3 4 6}

Who Is on the Research Team?

Mazen Dimachkie

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with Myasthenia Gravis (MG) grades 2 to 4A, who can commit to the study schedule and follow-up visits. They must have stable medication doses for at least 30-60 days and cannot be pregnant or breastfeeding without effective birth control. Those with severe psychiatric disorders, recent thymectomy, or participation in another study within the last three months are excluded.

Inclusion Criteria

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.

My myasthenia gravis is classified as mild, moderate, or severe.

I am willing to complete the study and attend all follow-up visits.

Exclusion Criteria

My condition has been severe but stable for the last 6 months.

I have a chronic illness that causes weakness or fatigue, but it's not myasthenia gravis.

You have experienced severe reactions to OAA in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either oxaloacetate or placebo for 8 weeks

8 weeks

Visits at weeks 2, 4, 6, 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Visits at weeks 10 and 12

What Are the Treatments Tested in This Trial?

Interventions

• Oxaloacetate
• Placebo

Trial Overview The trial tests oxaloacetate's effect on MG over a period of eight weeks: four weeks taking the drug and four weeks on placebo. Participants are divided into three groups receiving different doses to assess safety and potential benefits against muscle weakness caused by MG.

How Is the Trial Designed?

Group I: Oxaloacetate Active Control 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

Subjects will take 1000mg Placebo BID for 8 weeks.

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Terra Biological LLC

Industry Sponsor

Trials

7

Recruited

320+

Published Research Related to This Trial

In myasthenia gravis (MG), treatment strategies are tailored to disease severity, with acetylcholinesterase inhibitors being effective for mild cases, while more severe cases often require immunosuppressive treatments like azathioprine or glucocorticosteroids, which have been established through observational studies.

For severe and treatment-resistant MG, options like intravenous immunoglobulins and plasmapheresis are recommended, and surgical interventions such as thymectomy are advised for nonthymoma patients, significantly reducing perioperative risks when combined with immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the treatment of myasthenia gravis. Gold, R., Hohlfeld, R., Toyka, KV.[2021]

Acetylcholinesterase inhibitors remain the first-line treatment for myasthenia gravis (MG), but their effectiveness can diminish over time, leading to the need for additional therapies.

Immunosuppressive treatments, particularly steroids and adjunctive therapies like azathioprine and mycophenolate mofetil, are crucial for managing MG symptoms, though they come with potential side effects such as renal toxicity and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Actual aspects of myasthenia gravis treatment]. Czapliński, A., Radziwiłł, AJ., Steck, AJ.[2006]

In a study of 990 myasthenia gravis patients, 8.5% were identified as drug-refractory, meaning their condition did not improve with corticosteroids and multiple immunosuppressive agents, highlighting a significant challenge in treatment.

Among drug-refractory patients, only 42.9% achieved remission or minimal symptoms after a mean follow-up of 9.8 years, compared to 79.8% of non-drug-refractory patients, indicating a need for new, more effective treatments for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-refractory myasthenia gravis: Clinical characteristics, treatments, and outcome. Cortés-Vicente, E., Álvarez-Velasco, R., Pla-Junca, F., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04965987?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(Myasthenia%20gravis%20OR%20%22acquired%20myasthenia%22%20OR%20%22%20autoimmune%20myasthenia%20gravis%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING))&rank=5

NCT04965987 | Oxaloacetate in Myasthenia Gravis This is a phase 1 clinical trial studying whether or not oxaloacetate has a positive effect on patients with Myasthenia Gravis. Patients will be ...

2. withpower.com withpower.com/trial/phase-1-muscle-weakness-9-2021-24174

Oxaloacetate for Myasthenia Gravis · Info for Participants This trial is testing if oxaloacetate can help people with Myasthenia Gravis. Patients will take different doses of oxaloacetate over a period of time.

3. app.trialscreen.org app.trialscreen.org/trials/phase-1-myasthenia-gravis-oxaloacetate-trial-nct04965987

Oxaloacetate in Myasthenia Gravis Back to study results. A Phase 1 study of Oxaloacetate in Myasthenia Gravis. Investigating the Effects of Oxaloacetate in Patients with Myasthenia Gravis.

4. ctv.veeva.com ctv.veeva.com/study/oxaloacetate-in-myasthenia-gravis

Oxaloacetate in Myasthenia Gravis - ClinicalTrials.Veeva This is a phase 1 clinical trial studying whether or not oxaloacetate has a positive effect on patients with Myasthenia Gravis.

5. biospace.com biospace.com/new-study-oxaloacetate-reduces-chronic-fatigue-in-just-six-weeks-promising-data-for-me-cfs-patients

New Study: Oxaloacetate Reduces Chronic Fatigue In Just ... A new study reports significantly reduced mental and physical fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID patients.

6. synapse.patsnap.com synapse.patsnap.com/disease/f3433922efe24dfaada77415e3e66ea0

Myasthenia Gravis - Drugs, Targets, Patents ... Oxaloacetate in Myasthenia Gravis ... Ravulizumab Treatment Outcomes in Patients With Generalized Myasthenia Gravis (gMG) Naive to Complement Inhibitors.