View clinical trials related to Mitochondrial Diseases.
Filter by:This study is an observational longitudinal study involving the use of MRIs and video recordings taken at home of patients completing basic tasks. Once consent is obtained, subjects will be asked to schedule an appointment with radiology to undergo the listed MRIs of the heart and/or muscle. Subjects will also be given instructions on how to use the video recording app on their personal devices, or study provided device. The subjects will be followed regularly over the course of two years, submitting video recordings of their movements and reporting to Mayo Clinic for MRIs as scheduled.
The MiSBIE study collects biological, behavioral, psychosocial, neuropsychological, and brain imaging data in participants with either: normal mitochondrial function, individuals with the m.3243A>G mitochondrial DNA (mtDNA) mutation, and individuals a single large-scale mtDNA deletion. These defects induce mitochondrial allostatic load (MAL). The 2-day protocol, plus home-based data collection, will provide a comprehensive assessment of the multi-systemic dysregulation associated with MAL or mitochondrial dysfunction, and the link to physical and mental health-related symptoms. Aim 1: Determine the influence of MAL on systemic AL biomarkers. Aim 2: Establish the influence of MAL on stress reactivity profiles. Aim 3. Examine the association between MAL and psychological functioning.
A Phase I, Open-label, Fixed-sequence, Crossover, Drug-drug Interaction Study to Investigate the Inhibition Potential of KL1333 on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in Healthy Subjects
This is an open-label, multi-centre study in subjects with a genetically confirmed mitochondrial deoxyribonucleic acid (DNA) transfer ribonucleic acid (tRNA)Leu(UUR) m.3243A>G mutation who completed study KH176-202. In the KH176-203 study subjects will be receiving KH176 100 mg BID or KH176 50 mg bid in die (BID) (as determined by the investigator based on safety / tolerability considerations) for a year, thereby ensuring continued treatment with KH176 after study KH176-202. A final follow-up visit is scheduled 4 weeks after the intake of the last dose of study medication for patients not rolling over into the compassionate use program. Primary safety data and secondary efficacy (endpoint) data will be monitored and reviewed every three months by an independent Data Safety Monitoring Board (DSMB) to evaluate potential risks and benefits.
The purpose of the study is to systematically characterize the clinical course of the progressive neuropathy and optic atrophy observe in pediatric and adult patients with biallelic mutations in the solute carrier family 25 member 46 (SLC25A46) gene.
The purpose of the study is to systematically characterize the clinical course of the progressive neuropathy and optic atrophy observe in pediatric and adult patients with biallelic mutations in the ferredoxin reductase gene.
This is a parallel-arm, double-blind, placebo-controlled study with a screening phase that includes a 28-day run-in phase to establish baseline seizure frequency, followed by a 24-week, randomized, placebo-controlled phase. After completion of the randomized, placebo-controlled phase, participants may enter a 48-week, long-term, extension phase during which they will receive open-label treatment with vatiquinone.
Mitochondrial diseases, estimated prevalence 1 in 4,300 adults, is caused by pathogenic mutations in genes finally encoding for mitochondrial proteins of the various enzyme complexes of the OXPHOS. Among these mutations, the 3243A>G nucleotide change in the mitochondrially encoded transfer RNALeu(UUR) leucine 1 gene (MT TL 1) is the most prevalent one. The OXPHOS dysfunction resulting from such mutations leads to increased production of reactive oxygen species (ROS), ultimately leading to irreversible oxidative damage of macromolecules, or to more selective and reversible redox modulation of cell signaling that may impact (adult) neurogenesis. Despite advances in the understanding of mitochondrial disorders, treatment options are extremely limited and, to date, largely supportive. Therefore, there is an urgent need for novel treatments. KH176, a new active pharmaceutical ingredient (API), is an orally bio-available small molecule under development for the treatment of these disorders (see Section 1.4). The current study will further evaluate the effect of KH176 in various cognitive domains and evaluate the effect of different doses of KH176 (See Section 1.5). In view of the growing recognition of the importance of mitochondrial function in maintaining cognitive processes in the brain, as well as the understanding of the safety profile and pharmacokinetics of KH176 following the two clinical studies described above, a more detailed study is indicated of the effects of KH176 in various cognitive domains, using the confirmed safe and well-tolerated KH176 dose of 100 mg bid, as well as a lower dose of 50 mg bid. The primary objective is an evaluation of KH176 in the attention domain of cognitive functioning, as assessed by the visual identification test score of the Cogstate computerised cognitive testing battery.
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.
Mitochondrial diseases are complex diseases with great clinical and genetic heterogeneity and their diagnosis is difficult. The Medical Genetics Department includes among its activities the diagnosis of these diseases. It has been a reference centre for mitochondrial diseases at the national level since 2006 and was recently approved under the call for projects "European Reference Network (ERN) for rare diseases", EURO-NMD, supported by the Nice University Hospital. The routine diagnostic strategy is based on high throughput mitochondrial DNA (mtDNA) sequencing analysis and a panel of 281 targeted "mitochondriopathies" genes. When these analyses are negative, an exome analysis (high throughput sequencing of all exons in the genome) can be performed in a research setting. To date, about 40% of the patients analysed remain without genetic diagnosis. Indeed, it does not allow to identify large variations of deletion, duplication or CNV (copy number variation) type. Moreover, targeting only exons, exome sequencing does not allow the detection of intronic or localized mutations in regulatory regions. The identification of CNVs is made possible by chromosomal analysis on a DNA chip (CADC). This recognized technique is used routinely in the laboratory. The investigators use chips with a minimum resolution of approximately 13Kb for the genome-wide study of CNVs in patients with developmental disorders. However, this resolution is insufficient to detect rework events of the order of magnitude of an exon. There are high-resolution DNA chips, compatible with our platform, that would allow the investigators to more accurately visualize smaller rearrangements that could not be identified by exome analysis. The combined exome/CADC strategy has already proven its effectiveness in diagnosing various diseases by increasing yield. In this context, the investigators aim to use this strategy in this non-interventional study on a series of 15 patients with mitochondrial disease who remain undiagnosed after analysis of mtDNA, gene panel and exome. They will test 2 types of patients: - In the first series, whose disease is supposed to be transmitted in an autosomal recessive mode, only one heterozygous variant was identified in a gene already described in a comparable clinical picture. It is therefore possible that these patients are carriers on the second allele of a CNV, which the exome sequencing could not identify. - In the second series, the exome analysis did not allow the identification of a single responsible gene (several candidate genes without any certainty on the pathogenicity of the gene(s) or variant(s))