Glycerol Tributyrate for MELAS Syndrome and Optic Neuropathy
What You Need to Know Before You Apply
What is the purpose of this trial?
This is a parallel arm non-randomized dose-escalation, open-label basket exploratory phase 1 clinical trial where Mitochondrial encephalopathy, lactic acidosis, stroke-like episodes (MELAS) and Leber's hereditary optic neuropathy-Plus (LHON-Plus) participants will undergo simultaneous enrollment in two disease-based arms and receive daily oral doses of glycerol tributyrate to assess its safety and potential for efficacy using clinical, biochemical, and molecular evidence.This study will utilize a two-month baseline lead-in phase to establish and document the clinical baseline for each participant in both arms in order to compare the molecular and clinical parameters. This is clinically relevant in light of the high clinical heterogeneity among subjects affected by the same mitochondrial disease (MELAS or LHON-Plus). For ethical concerns prompted by the lack of treatment for these two intractable and progressive mitochondrial diseases, there will not be a placebo control group. Thus, each participant will act as their own control and receive oral doses of glycerol tributyrate, eliminating the need for a placebo. Considering the high clinical heterogeneity among participants affected by MELAS or LHON-Plus and some clinical divergence between MELAS and LHON-Plus, this strategy is beneficial to every enrolled participants, as each will receive the investigational drug, glycerol tributyrate. In addition, this approach will determine the subject-specific maximal optimized dose in a personalized medicine-based approach.After approval of the IRB protocol from the Institutional Review Board Data and signed consent form from all participants, this investigational basket clinical trial has three phases spanning over 20 months:* A baseline lead-in phase (2 months) to collect participant-specific baseline for clinical, biochemical, molecular and metabolic biomarkers that will be monitored throughout the subsequent dose-escalation and clinical phases.* A dose-escalation phase (6 months) to determine the participant-specific maximum tolerated dose (MTD) during which participant-specific clinical and biochemical biomarkers are collected every month.* A clinical phase at a fixed subject-specific MTD dose (12 months) to collect participant-specific clinical, biochemical, molecular and metabolic biomarkers and to perform three scheduled skin biopsies: at the outset, mid-point, and the end of this clinucal phase. We have planned for a 12-month-long clinical phase at a fixed participant-specific MTD considering the absence of reliable predictors that makes idiosyncratic disease-specific symptoms for MELAS and LHON-Plus impossible to forecast among participant for assessing the potential efficacy of glycerol tributyrate by monitoring clinical symptoms specific for each disease. During the 12-month-long time-frame, disease-specific clinical symptoms will be collected as preliminary evidence of efficacy of glycerol tributyrate using disease-specific biomarkers.Finally, discharge procedure during which the clinical investigator will record non-serious adverse events or serious adverse events for 7 or 30 days, respectively, after the last day of study participation.
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 Glycerol Tributyrate safe for humans?
How does the drug Glycerol Tributyrate differ from other treatments for MELAS Syndrome and Optic Neuropathy?
Glycerol Tributyrate is unique because it is being explored for its potential to address metabolic issues in MELAS Syndrome and Optic Neuropathy, conditions for which there are no standard treatments. This drug may offer a novel approach by targeting underlying metabolic pathways, unlike existing therapies that primarily focus on managing symptoms.16789
What data supports the effectiveness of the treatment Glycerol Tributyrate for MELAS Syndrome and Optic Neuropathy?
Research on similar treatments, like glycerol trioleate and glycerol trierucate (components of Lorenzo's oil), shows they can reduce very-long-chain fatty acid levels, which are linked to certain neurological conditions. However, there is no direct evidence of their effectiveness for MELAS Syndrome and Optic Neuropathy.12679
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
Exclusion Criteria
Timeline for a Trial Participant
Baseline Lead-in
Participants undergo a baseline lead-in phase to collect clinical, biochemical, molecular, and metabolic biomarkers.
Dose-Escalation
Participants receive escalating doses of glycerol tributyrate to determine the maximum tolerated dose (MTD).
Clinical
Participants receive a fixed participant-specific MTD of glycerol tributyrate to assess efficacy and safety.
Follow-up
Participants are monitored for adverse events and safety after the clinical phase.
What Are the Treatments Tested in This Trial?
Interventions
- Glycerol Tributyrate
Find a Clinic Near You
Who Is Running the Clinical Trial?
George Washington University
Lead Sponsor
Children's National Research Institute
Collaborator
National Center for Advancing Translational Sciences (NCATS)
Collaborator