RightFit
Not yet recruitingPhase 1 / Phase 2

A Basket Clinical Study to Assess Glycerol Tributyrate in Patients With Mitochondrial Encephalopathy, Lactic Acidosis, Stroke-like Episodes (MELAS) or Leber's Hereditary Optic Neuropathy-Plus (LHON-Plus)

Investigational Study of Glycerol Tributyrate in MELAS and LHON-Plus

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 65 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Physical exams, MRI scans, Spinal tap (lumbar puncture), Questionnaires, Pills

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Physical examination 5. 6-minute-walk test 6."
  • "Baseline MRI (for subjects with MELAS or LHON-Plus) and MRS (for MELAS subjects) 9."
  • "Lumbar puncture for LHON-Plus subjects to assess CSF markers for multiple sclerosis-like: * A specific group of antibodies referred to as oligoclonal bands * Myelin basic proteins (MBP) * IgG levels * Levels of inflammasome proteins * Leukocytes count: lymphocytes (B-cells and T-cells), monocytes, macrophages, plasma cells, and granulocytes * CSF/serum glucose ratio 16."
  • "Quality of Life (QoL) is assessed using the short questionnaire "Neuro-Quality of life" 18."
  • "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."
  • "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."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety of daily glycerol tributyrate capsules and whether they may help adults with MELAS or LHON-Plus, diseases that affect how cells make energy. The study lasts 20 months and finds the highest dose each person can tolerate. Everyone receives the study drug; no one receives a placebo (a pill with no active drug).

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 18 to 65 years old.
  • Have MELAS or LHON-Plus confirmed by a genetic test.
  • For MELAS: have symptoms and the m.3243A>G gene change, or a disease-causing change only in a mitochondrial gene for Complex I, which helps cells make energy.
  • For LHON-Plus: have symptoms and the m.11778G>A gene change, or a disease-causing change only in a mitochondrial gene for Complex I.
  • Have normal activity of Complex II, another part of the cell's energy-making system.
  • Be able to swallow capsules and follow study rules, as judged by the study doctor.
  • Be able to give written consent for yourself after learning about the study.
  • Use effective birth control during the study if sexually active or able to have children.

Who can't join

  • Have a history of another primary mitochondrial disease, or be acutely ill.
  • Be pregnant or breastfeeding, or have a positive urine pregnancy test within 7 days before the first dose.
  • Be in another mitochondrial disease trial now or within the past 6 months, or currently take another experimental treatment.
  • Have no nerve or brain symptoms, muscle weakness, or trouble tolerating exercise.
  • Have had severe symptoms rated grade 3 or higher in the past 6 months: nausea, vomiting, diarrhea, low or high blood sugar, dizziness, blurred vision, or fainting.
  • Have a known allergy to an inactive ingredient in the study drug, or currently misuse drugs or alcohol.
  • Be unable to give consent for yourself, or use a feeding tube.
  • Be unable to travel to the study site.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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

Study sites (1)

DC