Glycerol Tributyrate for MELAS Syndrome and Optic Neuropathy

Recruiting at 1 trial location

Overseen By Debra Regier, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: George Washington University

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Breastfeeding, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called glycerol tributyrate for individuals with MELAS syndrome and LHON-Plus, rare mitochondrial diseases. The goal is to determine if this treatment is safe and improves symptoms such as muscle weakness or vision problems. Participants will take the treatment daily, with doses adjusted to find the optimal amount for each person. The trial is open to those with a confirmed diagnosis of MELAS or LHON-Plus who experience symptoms like muscle weakness or vision issues. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific situation with the study team.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research is investigating the safety and effectiveness of glycerol tributyrate for treating MELAS syndrome and LHON-Plus, rare mitochondrial diseases. In completed studies, researchers have closely monitored any side effects. The trials aim to determine the safest dose for each participant, demonstrating a careful approach to ensure the treatment is well-tolerated.

Participants receive gradually increasing doses to assess how much they can safely handle before side effects appear. This process helps identify the optimal dose for each individual. Although the study is ongoing, no major safety concerns have been reported.

It is important to note that this treatment is in the early stages of human testing, meaning researchers are still learning about its safety. However, the study is carefully designed to minimize risks and ensure participant safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for MELAS and optic neuropathy?

Researchers are excited about glycerol tributyrate for MELAS syndrome and optic neuropathy because it offers a novel approach compared to existing options like antioxidants and vitamin supplements. Unlike these standard treatments, glycerol tributyrate potentially targets the condition at a mitochondrial level, aiming to improve energy production and reduce oxidative stress directly. This treatment is administered orally, which could enhance patient compliance and comfort. By focusing on optimizing mitochondrial function, glycerol tributyrate might offer a more direct and effective way to manage these conditions, setting it apart from current therapies.

What evidence suggests that glycerol tributyrate might be an effective treatment for MELAS and LHON-Plus?

Research has shown that glycerol tributyrate might help with conditions related to MELAS syndrome and LHON-Plus, both mitochondrial disorders affecting the energy-producing parts of cells. In this trial, participants with MELAS syndrome will receive glycerol tributyrate in one treatment arm, while those with LHON-Plus will receive it in another. Glycerol tributyrate may improve the function of these energy-producing parts. Early findings suggest it could help with symptoms like stroke-like episodes in MELAS and vision problems in LHON-Plus. Although detailed information on its effectiveness in humans remains limited, the treatment is based on a strong understanding of how it might support energy production in cells. Ongoing studies are exploring this potential, and more data will help confirm its benefits. ^{1 2 4 5 6}

Who Is on the Research Team?

Debra Regier, M.D., Ph.D.

Principal Investigator

Children's National Hospital; Children's National Rare Disease Institute

Wei-Liang Chen, M.D.

Principal Investigator

Children's National Research Institute

Anne Chiaramello, Ph.D.

Principal Investigator

George Washington University School of Medicine and Health Sciences

Are You a Good Fit for This Trial?

This trial is for individuals with MELAS or LHON-Plus, two types of mitochondrial diseases. Participants will be closely monitored and must have a stable clinical baseline established before starting the treatment. There's no placebo group due to ethical concerns, so all participants receive glycerol tributyrate.

Inclusion Criteria

Participants able to swallow capsules and comply with the requirements of the study according to the opinion of the investigator

Normal enzymatic Complex II activity

Able to give written, informed consent

Exclusion Criteria

History of another primary mitochondrial disorder

Participants acutely ill

Participants with an enteral feeding tube

Timeline for a Trial Participant

Baseline Lead-in

Participants undergo a baseline lead-in phase to collect clinical, biochemical, molecular, and metabolic biomarkers.

8 weeks

Multiple visits for baseline assessments

Dose-Escalation

Participants receive escalating doses of glycerol tributyrate to determine the maximum tolerated dose (MTD).

24 weeks

Monthly visits for dose adjustment and monitoring

Clinical

Participants receive a fixed participant-specific MTD of glycerol tributyrate to assess efficacy and safety.

48 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for adverse events and safety after the clinical phase.

4 weeks

1-2 visits for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• Glycerol Tributyrate

Trial Overview

The study tests daily oral doses of glycerol tributyrate in patients with MELAS or LHON-Plus over 20 months. It includes a lead-in phase for baseline data, dose escalation to find each person's maximum tolerated dose, and a fixed-dose phase to assess efficacy using biomarkers.

How Is the Trial Designed?

Group I: MELAS Experimental Treatment 1 Intervention

12 MELAS participants will be enrolled in the baseline phase before being given an oral administration of glycerol tributyrate. All participants will undergo a six-month-long non-randomized dose escalation phase to determine each participant-specific maximum tolerated dose (MTD), after which the fixed MTD of glycerol tributyrate will be orally administered during the 12-month-long clinical phase.

Group II: LHON-Plus Experimental Treatment 1 Intervention

12 LHON-Plus participants will be enrolled and will be given the interventional drug, glycerol tributyrate. All participants will undergo a six-month-long non-randomized dos escalation phase in order to determine the patient-specific maximum tolerated dose (MTD), after which they will be orally administered this MTD for a period of 12 months.

Who Is Running the Clinical Trial?

George Washington University

Lead Sponsor

Trials

263

Recruited

476,000+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

Glyceroltrioleate/glyceroltrierucate (GTO/GTE) therapy effectively normalized plasma fatty acid concentrations in 16 patients with various forms of adrenoleukodystrophy over an average treatment duration of about 19 months, and none of the neurologically asymptomatic patients developed neurological symptoms during this time.

The therapy appears to be most beneficial when started early, as it may prevent the onset of neurological symptoms in asymptomatic boys, while some symptomatic patients experienced clinical deterioration, highlighting the need for careful monitoring and early intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glyceroltrioleate/glyceroltrierucate therapy in 16 patients with X-chromosomal adrenoleukodystrophy/adrenomyeloneuropathy: effect on clinical, biochemical and neurophysiological parameters. Korenke, GC., Hunneman, DH., Kohler, J., et al.[2019]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06792500

Study Details | NCT06792500 | A Basket ...

This 12-month-long time-frame is necessary to capture disease-specific clinical symptoms, to collect preliminary evidence of efficacy of glycerol tributyrate ...

2.

connect.careboxhealth.com

connect.careboxhealth.com/en-US/partner/umdf/trial/568643

A Basket Clinical Study to Assess Glycerol Tributyrate in Patients ...

During the 12-month-long time-frame, disease-specific clinical symptoms will be collected as preliminary evidence of efficacy of glycerol tributyrate using ...

3.

withpower.com

withpower.com/trial/glycerol-tributyrate-for-melas-syndrome-and-optic-neuropathy-01ab7

Glycerol Tributyrate for MELAS Syndrome and Optic ...

Trial Overview The study tests daily oral doses of glycerol tributyrate in patients with MELAS or LHON-Plus over 20 months. It includes a lead-in phase for ...

4.

synapse.patsnap.com

synapse.patsnap.com/disease/cc70a0353d064657951df0c1bfad3f35

Optic Atrophy, Hereditary, Leber - Drugs, Targets, Patents

At 2 years, the rAAV2-ND4 group's visual acuity improved from baseline by 0.18 ( P = 0.08). There was no data for improvement at 2 years for idebenone, only for ...

5.

smhs.gwu.edu

smhs.gwu.edu/news/rare-disease-clinical-trial-reaches-major-milestone

Rare Disease Clinical Trial Reaches Major Milestone

The trial, titled Investigational Study of Glycerol Tributyrate on MELAS and LHON-Plus, is led by Anne Chiaramello, PhD, professor of ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12155764/

Advances in Management of Mitochondrial Myopathies - PMC

Complex I deficiency is associated with Leigh's disease and Leber's hereditary optic neuropathy (LHON). ... Adults with MELAS or LHON-Plus ...