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NCT06792500
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.
NCT06402123
PRIZM is a Phase 2b randomized, double-blind, placebo-controlled, 3-treatment, 2-period, crossover study evaluating the efficacy and safety of oral zagociguat 15 and 30 mg vs. placebo when administered daily for 12 weeks in participants with genetically and phenotypically defined MELAS.
NCT06644534
This is a randomized, double-blind, placebo-controlled study. Prior to treatment, patients will undergo a screening visit. If eligible, each subject will return for a Day 1 visit and will receive their first dose of investigational product (TTI-0102 or placebo). At the end of the first week of treatment, subjects will return for a Week 1/Day 8 study visit to assess study drug dosing/tolerance and instruct on dosing for the upcoming second week of treatment. For the first 8 weeks of treatment, subjects will alternate between returning to the clinic for detailed assessments (Weeks 4 and 8) and receiving a telephone call from the Investigator team to assess safety and TTI-0102 dose (Weeks 2 and 6) and the potential need for an immediate unscheduled study visit. After the first 8 weeks of treatment, subjects will continue to return to the clinic for monthly assessments at Weeks 12, 16, 20. The Study Exit visit will occur at Week 24, and subjects will be offered to continue on an open-label extension study of TTI-0102. If a subject does not complete the study, they will be asked to return for a Study Exit visit 4 weeks after last study drug dose. Primary Objective The primary objective of this study is to assess the efficacy, safety and tolerability of oral TTI 0102 compared to placebo, for up to 6 months in patients with MELAS. Secondary Objective The secondary objectives of this study are to assess the efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of cysteamine after oral administration of TTI-0102 at steady state, in patients with MELAS on a stable dose of TTI-0102. This is a randomized, double-blind, placebo-controlled study. Prior to treatment, patients will undergo a screening visit. If eligible, each subject will return for a Day 1 visit and will receive their first dose of investigational product (TTI-0102 or placebo). At the end of the first week of treatment, subjects will return for a Week 1/Day 8 study visit to assess study drug dosing/tolerance and instruct on dosing for the upcoming second week of treatment. For the first 8 weeks of treatment, subjects will alternate between returning to the clinic for detailed assessments (Weeks 4 and 8) and receiving a telephone call from the Investigator team to assess safety and TTI-0102 dose (Weeks 2 and 6) and the potential need for an immediate unscheduled study visit. After the first 8 weeks of treatment, subjects will continue to return to the clinic for monthly assessments at Weeks 12, 16, 20. The Study Exit visit will occur at Week 24, and subjects will be offered to continue on an open-label extension study of TTI-0102. If a subject does not complete the study, they will be asked to return for a Study Exit visit 4 weeks after last study drug dose. Study Drug Dosing To prevent any manifestation of intolerance at the initiation of drug treatment, only half a dose (2.75 grams) will be given once a day for the first week of treatment. During the following weeks of treatment, patients will be given a full dose of 5.5 grams once a day. Interim Data Review After nine (9) patients have completed three months of treatment (the Week 12 visit) an interim data cut will take place to assess safety and potential efficacy signals. Even if no indications of efficacy are detected at this early stage, the trial itself will not be terminated unless there is a serious safety concern (i.e., protocol-defined Stopping Criteria are met).
NCT05554835
The main goal of the project is provision of a global registry for mitochondrial disorders to harmonize previous national registries, enable world-wide participation and facilitate natural history studies, definition of outcome measures and conduction of clinical trials.
NCT03888716
This will be a double blind, randomised, placebo controlled, single and multiple oral dose study conducted in 3 parts: Part A, Part B and Part C. Part A and Part B include healthy volunteers only and will be completed before Part C including patients with primary mitochondrial disease will be initiated. The starting dose in the first cohort of Part A will be 25 mg. The dose level in the additional cohorts will be decided following review of data of the previous cohorts.
NCT01339494
Introduction Baylor College of Medicine and Texas Children's Hospital are recruiting individuals with MELAS syndrome for a clinical study. MELAS syndrome is a mitochondrial disease; patients with this disease have muscle weakness and often develop brain strokes, where blood does not flow normally to different parts of the brain. It is believed that these strokes could be due to decreased production of nitric oxide, a naturally occurring compound important for normal blood vessel function. Nitric oxide is made from arginine and citrulline that are normally found in our bodies. What is the purpose of this study? The purpose of this study is to measure nitric oxide in individuals with MELAS and see if giving arginine or citrulline will increase the formation of nitric oxide. Nitric oxide is thought to be helpful in preventing strokes. Therefore, if arginine and/or citrulline are shown to increase the formation of nitric oxide, they could be used to prevent or treat the strokes in patients with MELAS syndrome.
NCT02114554
Mitochondrial diseases are multisystem disorders that present with a wide range of clinical manifestations. Mitochondrial DNA nt3243A\>G mutation is one of the most common mutations seen in mitochondrial diseases. Syndromes associated with this mutation include mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), myoclonic epilepsy with ragged red fibers (MERRF), and chronic progressive external ophthalmoplegia (CPEO). Clinical analyses of mitochondrial DNA nt3243A\>G mutation from Taiwan remain scarce. The present study aims to investigate the clinical features and prognostic factors of patients with mt3243A\>G mutation in Taiwan.
NCT01603446
MELAS patients suffer from exercise intolerance, weakness, poor vision or blindness, poor growth, developmental delay, and deafness. They also have unique 'stroke-like' episodes (SLEs) which are not due to blockages of large or medium arteries. These 'strokes' are thought to be due to energy failure of very small brain blood vessels combined with energy failure in the mitochondria (cell battery) of the brain cells, especially in the back region of the brain in the vision centre. This leads to visual loss and paralysis. The overall goal of this study is to better understand the mechanism of these SLEs at the level of the brain cells and small blood vessels.