Tests glycerol tributyrate by mouth in adults with MELAS or LHON-Plus

Trial details

Who runs it

George Washington University

Trial code

NCT06792500

Record updated

5 October 2026

Original description

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.Read full original descriptionShow less

Investigational Study of Glycerol Tributyrate in MELAS and LHON-Plus

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.

Inclusion: Participants must be aged 18 to 65 years; A confirmed molecular diagnosis of MELAS or LHON-Plus; Symptomatic participants with MELAS harboring the m.3243A>G variant or a mitochondrial pathogenic variant solely mapping in a mitochondrial gene encoding a mitochondrial subunit of Complex I; Symptomatic participants with LHON-Plus harboring the m.11778G>A or a mitochondrial pathogenic variant only mapping in a mitochondrial gene encoding a mitochondrial subunit of Complex I; Normal enzymatic Complex II activity; Participants able to swallow capsules and comply with the requirements of the study according to the opinion of the investigator; Able to give written, informed consent; Participants who are sexually active and/or fertile must use an effective birth control during the study.

Exclusion: • History of another primary mitochondrial disorder; Participants acutely ill; Positive urine pregnancy test for female subjects of childbearing potential within seven days prior to the first dose of the investigational drug; Pregnancy and/or breastfeeding; Participating in another mitochondrial disorder trial; Participated in another mitochondrial disorder trial within the last six months; On a current therapy with other investigational agents; Absence of neurological symptoms, muscle weakness, or exercise intolerance; Presence of any of the following signs or symptoms in the past six months at grade 3 or higher based on the CTCAE version 4.03: nausea, vomiting, diarrhea, hypoglycemia, hyperglycemia, dizziness, blurred vision, or syncope; A known hypersensitivity to any excipient contained in the drug formulation; Current abuse of drugs and/or alcohol; Unable to consent for themselves; Participants with an enteral feeding tube; Inability to travel to the study site.

ClinicalTrials.gov NCT06792500