A Phase 1/2 interventional study of Glycerol Tributyrate in MELAS Syndrome and Lebers Hereditory Optic Neuropathy With Extra Ocular Symptoms (LHON-Plus), sponsored by George Washington University. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-05.
Sponsored by George Washington University · Phase 1/2, Interventional, and Treatment
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:
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.
During the two-month-long baseline lead-in phase, we will acquire the following information, which are part of standard clinical care:
Clinical laboratory biomarkers completed and/or interpreted at the CLIA-certified labs at Children's National Hospital:
Lumbar puncture for LHON-Plus subjects to assess CSF markers for multiple sclerosis-like:
Skin biopsy to assess:
Mitochondrial Stress Test assay: This assay measures the baseline of the participant's mitochondrial functions by quantifying OXPHOS bioenergetic parameters. The investigators uses this assay to monitor the potential efficacy of oral administration of glycerol tributyrate in participants.
Real-Time ATP Rate assay: The investigators use this assay to quantify the pathway-specific ATP rate production from the mitochondrial OXPHOS pathway and the cytosolic glycolytic pathway.
Agilent Glycolytic Rate assay: The investigators use this assay to assess the metabolic plasticity between the two main energy pathways, OXPHOS and glycolysis,as well as to correlate one-on-one the glycolytic activity with lactate accumulation.
No participants are enrolled in the dose-escalation phase without a complete interpretation of the clinical data from the baseline lead-in phase. As a higher level of safety risk, participants with the pre-existing severe complications, renal failure, arrhythmia, pneumonia with respiratory failure, and/or severe gastroparesis, will be excluded from progressing to the dose-escalating phase.
During the six-month-long dose-escalation phase, the investigators will determine the safe participant-specific MTD using the toxicology and clinical data described above.
Participants are administered glycerol tributyrate three times a day (tid) dispensed by the Children's National Hospital (CNH) research pharmacy located in the study site (CNH). To initiate the dose-escalation phase, the investigator provides all participants with a one-month supply of 100 capsules, each containing 500 mg of glycerol tributyrate. The initial dose is 1000 mg tid. During the last week of month 1 and subsequent months, the investigators review the clinical and biochemical data for each participant before increasing the oral dose of glycerol tributyrate.
Below is the description of the methods to assess for dose-limiting toxicity (DLT) throughout the dose-escalation phase.
Disease-specific assessment:
General toxicity assessment: The clinical investigators evaluate toxicity using the Common Terminology Criteria of Adverse Events (CTCAE) version 4.0 3 grading scale.
At the conclusion of the dose-escalation phase, a skin biopsy will be performed on all participants prior to the onset of the clinical phase at fixed participant-specific MTD. The participant-specific dermal fibroblasts will be derived to determine the genetic and mitochondrial bioenergetic parameters for each participant at the outset of the clinical phase.
The 12 month-long clinical phase at fixed participant-specific MTD starts at the conclusion of the 6-month-long dose-escalation phase and is divided into two 6-month-long periods. This 12-month-long time-frame is necessary to capture disease-specific clinical symptoms, to collect preliminary evidence of efficacy of glycerol tributyrate using disease-specific biomarkers, and to assess possible clinical outcomes demonstrating clinical benefit of glycerol tributyrate.
At the outset, mid-phase, and end of the 12 month-long clinical phase, participants will undergo three skin biopsies to assess the potential efficacy of glycerol tributyrate on:
Throughout the clinical phase at fixed MTD, we will implement the same safety assessment for DLTs than for the dose-escalation phase.
At the end of the 12-month-long clinical phase at fixed participant-specific MTD, the investigators will discharge the participants after performing a follow-up study during which non-serious adverse events or serious adverse events will be recorded for 7 or 30 days, respectively, after the last day of study participation.
Capsules containing glycerol tributyrate (500 mg) will be administered orally to all participants three times a day with an 8-ounce glass of water on an empty stomach: morning, noon, and evening during the dose-escalation phase and the clinical phase at fixed subject-specific MTD of the study.
Compliance will be assessed with an electronic log/diary where participants will record on a daily basis time, date, and pill counts. Participants will be asked to bring back all the bottles of glycerol tributyrate to subsequent visits to assess compliance. Compliance will be considered satisfactory with 80% of planned doses logged in.
Participants will be specifically monitored for the occurrence of the following Adverse Events (AEs) graded based on the CTCAE v4.03:
A Data and Safety Monitoring Board (DSMB) committee has been formed and includes five independent members: a metabolic physician, neurologist, bioethicist, a clinical trialist, and a lay person as a non-voting member. The DSMB committee will review safety data on an ongoing basis, meet biannually or ad-hoc if the need arises. This additional oversight provided by a DSMB committee provides further protection to the study participants during the basket clinical trial for MELAS and LHON-PLus.
37 studies on the registry are indexed under MELAS Syndrome; 8 are open to participants now.
This study's planned enrollment of 24 is close to the median of 24 across 29 interventional studies indexed under MELAS Syndrome.
Browse MELAS Syndrome studies →George Washington University is the lead sponsor of 192 studies on the registry; 34 are open to participants now.
Of its 13 completed or terminated interventional studies of FDA-regulated products, 11 (85%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
History of another primary mitochondrial disorder
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Glycerol Tributyrate
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.
Drug: Glycerol Tributyrate
Participants will be administered orally three times a day enteric hard capsules containing 500 mg of glycerol tributyrate with an 8-ounce glass of water on an empty stomach: morning, noon, and evening during the dose-escalation phase. Each MELAS participant will undergo a six-month dose escalation phase of glycerol tributyrate, starting at a dose of 1,000 mg (tid) per day during the first month followed by a monthly increase of 500 mg (tid) per dose of glycerol tributyrate with the maximal oral dose of glycerol tributyrate 3,500 mg (tid) per dose at the end of six-month-long dose escalation phase. Once the participant-specific fixed maximum tolerated dose (MTD) is determined, MELAS participants will take an oral administration of this MTD three times a day during the 12-month-long clinical phase.
Assessment of Dose Safety for Glycerol Tributyrate
To assess the dose safety of the investigational drug, glycerol tributyrate, the investigators will measure Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\] using the CTCAE version 4.03
Time frame: 20 months
Potential Efficacy of Glycerol Tributyrate on the oxidative phsophorylation metabolism
The investigators will assess whether participant-specific maximum tolerated dose (MTD) of glycerol tributyate results in increase of the participant's bioenergetic parameters for the oxidative phosphorylation pathway and/or mitochondrial ATP rate production above the participant's baseline determined from a dermal fibroblasts derive from a skin biopsy during the two-month-long baseline lead-in phase.
Time frame: 20 months
Shared Secondary MELAS and LHON-Plus Outcome
Improved daily activity measured by actigraphy
Time frame: 20 months
Shared Secondary MELAS and LHON-Plus Outcome
Improved performance in the 6-minute-walking test
Time frame: 20 months
Shared Secondary MELAS and LHON-Plus Outcome
Reduced frequency of hospitalization prior to trial entry
Time frame: 20 months
Shared Secondary MELAS and LHON-Plus Outcome
Improved quality of life (QoL) using the Neuro-QoL
Time frame: 20 months
Shared Secondary MELAS and LHON-Plus Outcome
Reduced presence and perceived fatigue using the Modified Fatigue Impact Scale
Time frame: 20 months
MELAS-Specific Secondary Outcome Measure
Decreased frequency of seizures
Time frame: 20 months
MELAS-Specific Secondary Outcome Measure
Stable cortical brain lesions by magnetic resonance imaging
Time frame: 20 months
LHON-Plus Specific Secondary Outcome Measure
Stable hemoglobin A1C
Time frame: 20 months
LHON-Plus Specific Secondary Outcome Measure
Stable brain and spinal lesions by magnetic resonance imaging
Time frame: 20 months
LHON-Plus Specific Secondary Outcome Measure
Stable cerebrospinal fluid markers for Multiple Sclerosis-like presentations
Time frame: 20 months
MELAS-Specific Exploratory Outcome
Decreased blood and brain lactate levels, measured by plasma and magnetic resonance spectroscopy, respectively.
Time frame: 20 months
MELAS-Specific Exploratory Outcome
Stable cortical brain lesions by magnetic resonance imaging
Time frame: 20 months
LHON-Plus-Specific Exploratory Outcome
Improved visual acuity measured by Snellen chart
Time frame: 20 months
LHON-Plus Specific Exploratory Outcome Measure
Improved electromyography and nerve conduction velocity
Time frame: 20 months
LHON-Plus-Specific Exploratory Outcome Measure
Decreased Multiple Sclerosis-like presentations using the Expanded Disability Status Scale
Time frame: 20 months
Plan to share: No
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Tributyrin
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