Glycerol tributyrate for adults with MELAS or LHON-Plus
Investigational Study of Glycerol Tributyrate in MELAS and LHON-Plus
PHASE1; PHASE2 · George Washington University · NCT06792500
This trial will test daily oral glycerol tributyrate in adults with MELAS or LHON-Plus to check safety and look for signs it might help symptoms and biomarkers.
Quick facts
| Phase | PHASE1; PHASE2 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | George Washington University (other) |
| Locations | 1 site (Washington D.C., District of Columbia) |
| Trial ID | NCT06792500 on ClinicalTrials.gov |
What this trial studies
This is an open-label, parallel-arm, non-randomized dose-escalation Phase 1/2 basket trial testing daily oral glycerol tributyrate in adults with MELAS or LHON-Plus. Participants complete a two-month baseline lead-in to document clinical status and a panel of biochemical and molecular biomarkers before starting treatment. The study uses clinical exams, standardized functional tests, MRI/MRS, EEG, ophthalmologic testing, CSF studies for LHON-Plus, and CLIA-certified labs (including GDF-15, FGF-21, lactate, and others) to monitor safety and exploratory signals of efficacy. There is no placebo control for ethical reasons, and enrollment is at a single site with strict molecular inclusion criteria.
Who should consider this trial
Good fit: Symptomatic adults aged 18–65 with a confirmed molecular diagnosis of MELAS (for example m.3243A>G or other pathogenic mtDNA affecting Complex I) or LHON-Plus (for example m.11778G>A or similar Complex I mtDNA variants), with normal Complex II activity and ability to swallow capsules and attend study visits.
Not a fit: People with other primary mitochondrial disorders, abnormal Complex II activity, pregnant individuals, acutely ill patients, or those with pathogenic variants outside mitochondrial Complex I are unlikely to benefit from this specific trial.
Why it matters
Potential benefit: If successful, glycerol tributyrate could improve mitochondrial function and reduce clinical and biochemical signs of disease, potentially slowing progression or improving symptoms such as exercise tolerance or vision.
How similar studies have performed: This approach is largely exploratory in humans: there is limited clinical data but some preclinical and early-phase evidence that butyrate prodrugs can support mitochondrial metabolism and reduce disease markers.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Criteria: * • 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
Where this trial is running
Washington D.C., District of Columbia
- Children's National Hospital — Washington D.C., District of Columbia, United States (RECRUITING)
Study contacts
- Principal investigator: Debra Regier, M.D., Ph.D. — Children's National Hospital; Children's National Rare Disease Institute
- Study coordinator: Anne Chiaramello, Ph.D.,
- Email: achiaram@gwu.edu
- Phone: (202) 994-2173
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: MELAS Syndrome, Lebers Hereditory Optic Neuropathy With Extra Ocular Symptoms, Mitochondrial Disease, Pathogenic mitochondrial variants, ATP deficiency, Maternal inheritance, Stroke-like episodes, Chronic energy deficit