View clinical trials related to Mitochondrial Diseases.
Filter by:A previous NAMDC survey study (NAMDC 7414 - Diagnostic Odyssey Survey, referred to hereafter as Odyssey1), provided a benchmark account of the substantial challenges faced by patients in achieving a diagnosis of mitochondrial disease, and of the impact such a diagnosis has on them (Grier et al. 2018).1 This study was conducted from October 2015 through January 2016. We propose a new survey study (Odyssey2) which will provide an update, additional data collection (duration of the diagnostic odyssey), and allow assessment of next-generation DNA sequencing techniques since Odyssey1 concluded. Odyssey2 will retain the strengths (simplicity, brevity, confidentiality, and data quality assurance measures) which made Odyssey1 successful. While Odyssey2 adds some refinements based on experience learned from Odyssey1, the basic questions are changed as little as possible to maximize comparability, and the additions are limited. Odyssey1 consisted of between 16 and 23 questions, depending on skip patterns, and took an estimated 15 minutes to complete. Odyssey2 consists of between 23 and 33 questions, depending on skip patterns and we estimate that it will take approximately 20 minutes to complete. As in Odyssey1, only patients who report, directly or through a guardian, that they have been informed by a doctor that they have a confirmed mitochondrial disorder will be eligible for Odyssey2.
To test if a ketone-ester based drink can boost muscle mitochondrial function in vivo in patients with VLCADD in order to establish a rational basis for therapeutic use in this disorder.
Older adults with human immunodeficiency virus (HIV) and a long history of antiretroviral therapy have more mitochondrial dysfunction- the cells that help them make energy. This dysfunction in mitochondria may lead to symptoms of muscle fatigue, physical function impairment, and impaired exercise tolerance compared to HIV-uninfected controls of a similar age and body mass index (BMI). Furthermore, the investigators hypothesize that the older antiretroviral therapy (ART) of tenofovir disoproxil fumarate (TDF) is associated with greater impairment in mitochondrial function than the newer agent, tenofovir alafenamide (TAF).
Mitochondria are important parts of the cell that are responsible for producing energy. The amount of energy they produce depends on how much energy the body needs to function and this energy production can be severely impaired in people with mitochondrial disease. Symptoms of mitochondrial disease vary widely but usually involve the brain, nerves and muscles, as these are tissues that need a lot of energy. Mitochondrial disorders affect 1 in 5000 of the UK population and there is currently no cure. Some scientists think that increasing the number of mitochondria in the body (mitochondrial biogenesis) might be an effective treatment for the symptoms of mitochondrial disease. Studies carried out in mice have shown that a type of B-vitamin called Nicotinamide Riboside (NR) is able to increase the number of mitochondria, leading to increased energy and a reduction in the symptoms of mitochondrial disease. The aim of this study is to investigate if the same B vitamin, Nicotinamide Riboside, can increase energy production and reduce symptoms in humans with mitochondrial disease. The study will consist of two parts: Part 1: Participants will be given a single oral dose of Nicotinamide Riboside and the levels of NR in their bloodstream will be measured at regular intervals. This will involve a single overnight stay and simple blood tests. Part 2: This requires 6 separate visits from each participant. Each participant will undergo a series of standard tests including a muscle biopsy and an MRI scan, then they will take a course of Nicotinamide Riboside (twice daily for 4 weeks). After 4 weeks of treatment, the participants will undergo the same tests again to see if there have been any changes in response to the treatment.
Slow movement of patients guts is referred to as intestinal dysmotility, and is increasingly recognised as a debilitating manifestation of mitochondrial disease both in adults and children. To date, symptoms of slow gut movements have been managed with laxatives and drugs that increase movement of the guts with variable results. A low residue diet is a form of low fibre diet (<10g fibre per day) that is used to minimise symptoms of poor movement of the guts. This reduces fecal volume and bulk, and hence gut workload, ensuring limited bowel activity and colonic rest. It has been shown to be well accepted in other conditions associated with slow gut movements. However, its role in patients with mitochondrial disease is unknown. The investigators are particularly interested in: - Does a low residue diet (low fibre) cause a change in the number of stools per week and stool consistency? - Is a low residue diet tolerated well and easy to comply with? - Does a low residue diet reduce gut symptoms of abdominal pain, bloating, and constipation? - Does a low residue diet improve quality of life and disease burden? - Does a low residue diet affect the bacteria in the gut? - Can we prove by X-ray that movement of food through the gut is slowed in patients with mitochondrial disease, and whether a low residue diet alters the speed of movement of food through the gut? - Can a low residue diet change patients physical activity levels? - Does a low reside diet change dietary patterns and food intake? - Does a low residue diet alter anthropometrics, such as weight, body mass index and waist to hit ratio? - Can a low residue diet improve kidney and liver function and lipid profile in blood samples? The investigators hope that by looking at these areas that a low residue diet may be able to improve patients slow gut movements, health, quality of life and disease burden.
Mitochondrial diseases are a genetically heterogeneous group of disorders caused by mutations or deletions in mitochondrial DNA (mtDNA) displaying a wide range of severity and phenotypes. These diseases may be inherited from the mother (mitochondrial inheritance) or non-inherited. The latter are ultra-rare pediatric diseases caused by a mutation or deletion of mtDNA, which develop into a systemic multi organ disease and eventually death. MNV-BM-BLD is a therapeutic process for enrichment of patient's peripheral hematopoietic stem cells with normal and healthy mitochondria derived from donor blood cells. The process, called mitochondria augmentation therapy, aims to reduce the symptoms of mitochondrial diseases.
The purpose of this study is to test how different doses of a statin, Lipitor, affect muscle health and function, and cardiovascular fitness.
2622/5000 Mitochondrial diseases (MM) are the most common metabolic diseases. Since these pathologies are very heterogeneous in clinical terms, only the identification of mutations in nuclear genes or mitochondrial DNA confirms the diagnosis. The full-scale study of mtDNA by high-throughput sequencing (NGS) is a first step in the diagnostic approach. The recent introduction of this revolutionary new technology has greatly increased the efficiency of mutation identification. However, in addition to known pathogenic mutations, NGS reveals numerous variants whose significance is currently unknown. A major challenge to obtain a reliable diagnosis is therefore the interpretation of the clinical impact of these new rare variants which proves to be very difficult. Pathogenicity criteria allow the classification of variants from benign to pathogenic. One of the major pathogenicity criteria is a good correlation of heteroplasmic level with tissue or cellular involvement. Indeed, mtDNA mutations are generally heteroplasmic, which corresponds to the coexistence of normal and mutated molecules in the same cell or tissue, the most affected tissues having a high rate of mutation. On a muscle biopsy of an affected patient, the fibers often present an enzyme deficiency in cytochrome c oxidase (COX-negative) which can be demonstrated in immunohistochemistry. The single fiber study allows to isolate the deficient fibers and to quantify the heteroplasmic rate of a variant. The presence of a high level of heteroplasm in the COX-negative fibers, unlike fibers without deficit, is a strong argument in favor of the pathogenicity of this variant. Currently, this technique is not used routinely in diagnostic laboratories but only occasionally in a research framework in some laboratories. It is a heavy technique that consists of a first stage of laser microdissection of the various muscle fibers followed by a second step of quantification of the variant from each fiber. This second step requires a specific focus for each identified variant. The aim of this pilot study is to develop a new technique for quantification of single-fiber heteroplasmics isolated by NGS laser microdissection. This, independent of the type of variant, will avoid the long and costly adjustments required for each new variant identified and thus facilitate its use
Gastrointestinal (GI) dysmotility in patients with mitochondrial disease are increasingly recognized and often include dysphagia, abdominal pain, abdominal distention, bacterial overgrowth, constipation, and in severe cases surgery. Although the proposed pathological mechanisms underlying the development of GI dysmotility remain diverse, potential mechanisms include mitochondrial dysfunction of smooth muscle within the GI tract and visceral myopathy. Moreover, bacteria within the GI tract, termed 'gut microbiota' has also been identified as a key contributor towards GI dysmotility. Aim: The aim of this study is to assess the role that the gut microbiota has on clinical disease expression in patients with mitochondrial disease. Objectives: This is a feasibility study to assess: 1. How does clinical disease severity impact upon the gut microbiota in mitochondrial patients compared to healthy controls. 2. How diagnostic and therapeutic approaches for mitochondrial disease be improved. Methods: This is a pilot study and is part of the Newcastle Mitochondrial Research Biobank. Stool samples will be collected from patients with a Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes (MELAS) phenotype carrier of the m.3243 A>G mutation (N=20) from the United Kingdom Medical Research Council (MRC) Centre for Mitochondrial Disease Patient Cohort (RES/0211/7552, the largest cohort of mitochondrial patients in the world) and the mitochondrial clinic and age and gender matched healthy controls (N=20). DNA will be extracted from stool samples and the 16S rRNA gene (V4 region) will be sequenced. This data will be analysed using bioinformatics pipelines and computational biology. Long Term Goal: To generate novel information relating to how the gut microbiota impacts upon clinical disease expression. This information could then be used to build a predictive model designed to optimise diagnosis and therapeutic treatments. This method also holds potential for use as a model for ageing and diseases associated with mitochondria not working properly, such as diabetes, cancer and Parkinson's disease. This research has the potential to reduce costs to the NHS and improve patient care and their quality of life.
The overarching goal of this study is to determine the role of chronic kidney disease and the activation of the kallikrein-kinin system during hemodialysis on the development of mitochondrial dysfunction; the investigators will measure mitochondrial function using the gold standard method, 31-phosphorus magnetic resonance spectroscopy. The investigators will test the hypothesis that endogenous bradykinin promotes mitochondrial dysfunction in patients undergoing hemodialysis. The investigators will first perform a randomized, placebo-controlled, double-blind, cross-over study measuring the effect of Icatibant (HOE-140), a bradykinin B2 receptor blocker, on mitochondrial function.