Active clinical trials for "Mitochondrial Diseases"

The purpose of this study is to develop preliminary evidence, such as effect size and variance estimates, to guide successful conduct of a properly-powered clinical trial to assess the benefit of a mitochondrial cocktail (incorporating individualization of treatment) in Gulf War illness (GWI).

In this study, 50 children between 3 and 12 years old with formally diagnosed autistic spectrum disorders (ASD) and also having significant mitochondrial dysfunction will be treated for a 3 month period with the Mitochondrial Cocktail, a combination of specific nutritional supplements and metabolite intermediates (including anti-oxidants) and bio-energy substrates. A series of neurological and psychological evaluations will be conducted by trained evaluators/clinicians to evaluate both the severity and the clinical presentation of the ASD/mitochondrial dysfunction with each subject at baseline prior to treatment, after the 3 month treatment and again at 6 months, after another 3 month non-treatment period. In addition, laboratory investigations will be conducted at the same time-points to assess the mitochondrial dysfunction and cellular biomarkers thought to be associated with autistic and mitochondrial disorders. These investigations will include the analysis of samples of blood and cheek/buccal swabs collected from each child to assess select biochemical markers of ASD. The Mitochondrial Cocktail treatment will be administered at home once a day continuously for a total of 3 months. All the children in the study will be treated with the same Mitochondrial Cocktail (an open label study).

The major steps forward of the neurosciences in recent years have linked psychiatric diseases, neuropsychological symptoms and brain dysfunctions. The cerebral functioning requiring a big quantity of energy, mitochondria, essential organelles in the cellular energy processes, are at present considered as a way of research for big interest in neurology and in psychiatry. Thus, an increasing number of studies describe potential links between mitochondrial dysfunction and psychiatric symptomatology. The clinical symptomatology of children with mitochondrial cytopathy is varied. Well described neurologically and somatically, it is significantly less in its psychiatric aspects. However, psychiatric symptoms are frequently associated and this symptom has already been described in adult patients. The symptoms mainly include depressive and anxiety disorders, or even tables suggestive of psychotic disorders, which would precede the diagnosis of mitochondrial disease of 13 years on average. Neuropsychological disorders refer to disorders of the higher functions following a cerebral anomaly (language, praxis, motricity, gnosis, visual spatial processing, memory, attention, intelligence, executive functions ...). Tests validated in French and adapted to children and adolescents can identify neuropsychological disorders in these populations.

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: How does clinical disease severity impact upon the gut microbiota in mitochondrial patients compared to healthy controls. 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 investigators are conducting a research study on nutrition in mitochondrial disease. The investigators are interested in the kind of carbohydrates that people eat. Carbohydrates are an important source of energy. Certain kinds of carbohydrates tend to raise blood sugar more in healthy people, and others tend to raise blood sugar less in healthy people. The investigators would like to know if by eating the "right" type of carbohydrate, people with mitochondrial disease can avoid high lactate levels, high blood sugar levels, and, later, low blood sugars. In this study, this question will be answered by finding out how people with mitochondrial disease respond to two different test meals containing different kinds of carbohydrates. Neither participants nor the investigators will know which kind of test meal participants are eating.

This study will examine metabolic and biological factors in people with Li-Fraumeni syndrome, a rare hereditary disorder that greatly increases a person's susceptibility to cancer. Patients have a mutation in the p53 tumor suppressor gene, which normally helps control cell growth. This gene may control metabolism as well as cancer susceptibility, and the study findings may help improve our understanding of not only cancer but also other conditions, such as cardiovascular function. Healthy normal volunteers and patients with the Li-Fraumeni syndrome and their family members may be eligible for this study. Candidates must be at least 18 years of age, in overall good health and cancer-free within 1 year of entering the study. Participants undergo the following procedures: Blood tests for routine lab values and for research purposes. ECG and echocardiogram (heart ultrasound) to evaluate heart structure and function. Resting and exercise metabolic stress testing: The subject first relaxes in a chair wearing the facemask and then exercises on a stationary bicycle or treadmill while wearing the mask. This test uses the facemask to measure oxygen usage by the body to determine metabolic fitness. Electrodes are placed on the body to monitor the heart in an identical manner to a standard exercise stress test. Magnetic resonance imaging of metabolism: The subject lies on a bed that slides into a large magnet (the MRI scanner) for up to 60 minutes. During scanning, the arm or leg muscles are stressed by inflating a blood pressure cuff and by exercising the limb for several minutes. Subjects may be asked to squeeze a rubber ball or exercise with a foot pedal. Immediately afterwards, the pressure in the cuff is released and remains deflated for 10 to 15 minutes. No more than three 5-minute episodes of blood flow stoppage are performed. Standard MRI scan of exercised limb to determine muscle volume. Brachial artery reactivity test to measure blood vessel function: Before the exercise stress testing, subjects lie on a stretcher while the brachial artery (artery in the forearm) is imaged using a noninvasive ultrasound method. Artery size and blood flow velocity are measured before and after inflating a blood pressure cuff on the forearm. Vessel size and flow velocity measurements are repeated after 15 minutes and again after administration of nitroglycerin under the tongue. Oral glucose tolerance testing to test for diabetes: To assess sugar metabolism, subjects drink a sugar solution. Blood samples are collected before drinking the solution and 1 and 2 hours after drinking the solution. Muscle biopsy (optional according to subject preference): Subjects may be given small amounts of sedation for the procedure. A small area of skin over a leg muscle is numbed and a small amount of muscle tissue is surgically removed.

The objective of this research protocol is to continue investigation of the nature and prevalence of mitochondria disease and to aid patients and health care providers in the understanding of these complex disorders. This research study brings together many clinical sub-specialists to address the etiology of these disorders and to develop more effective approaches for their diagnoses and more reliable prognoses.

Mitochondrial disorders are a group of inherited disorders causing malfunctional mitochondria. Mitochondria are found in every cell of the body, and the disorders therefore give symptoms from every tissue, especially those with high energy needs as the brain, heart and muscles. The symptoms are often unspecific in terms of muscle weakness and fatigue, which delays the first contact to the doctor and further delays the diagnosis. The aim of this study is to investigate if it is possible to use GDF-15 (Growth and Differentiation Factor 15) as a biomarker for mitochondrial disease and compare the results with that of healthy controls, metabolic myopathies and muscular dystrophies. The concentration relative to exercise will further be investigated.

Hypothesis: Many patients with underlying mitochondrial disorders have feeding problems because of poor gastrointestinal motility; feeding problems lead to growth impairment and many affected children are malnourished.

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.