Active clinical trials for "Glycogen Storage Disease Type V"

Previous studies have indicated that 13C-MRS in the ultra-high 7T magnetic resonance (MR) field is a potential non-invasive measurement method for assessing changes in muscle glycogen levels in PoD patients. However, in a single study, increases in glycogen intermediates were observed using the even more sensitive 31P-MRS technique in a mouse model of PoD and in glycogen storage disease III in humans. In fact, glycolytic intermediates such as phosphomonoesters (PME), measured by phosphorus-31P-MRS in PoD mouse models, were superior to 13C-MRS in monitoring disease progression and quantifying glycogen, indicating a significant clinical potential of 31P-MRS in humans. It has been shown that 31P-MRS can reliably quantify age- and weight-related differences as well as changes in thyroid function in human muscle metabolism. This study conducted by our institute demonstrates that the technique possesses the necessary sensitivity to measure these subtle muscular metabolic changes. However, there are currently no human 31P-MRS muscle data available for PoD. Therefore, we propose a proof-of-principle study to address this knowledge gap and contribute to establishing a new sensitive muscular biomarker that quantifies the primary disease mechanism, namely glycogen formation, for future longitudinal studies on PoD.

The project will use carbon-13 magnetic resonance spectroscopy to assess whether high glycogen levels in skeletal muscle of patients with Glycogen Storage Diseases is a prelude for muscle damage. Patients with Glycogen Storage Diseases will be examined using carbon-13 MR-spectroscopy to quantify the glycogen levels in lumbar, thigh and calf-muscles. The pattern of glycogen concentration will be compared to the pattern of muscle atrophy found in the literature.

McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle. We hypothesize that a modified ketogenic diet could be a potential treatment option, by providing ketones as alternative fuel substrates for working muscle. In this open interventional pilot study we wish to investigate 3 different modified ketogenic diet regimes, to find an optimal composition of a modified ketogenic diet that ensures adequate degree of ketosis and at the same time is well tolerated for patients with McArdle disease.

Background: Patients with the sugar metabolism disorder, Glycogen Storage Disease Type V, have insufficient breakdown of sugar stored as, glycogen, within the cells. The investigators know from previous studies with McArdle patients, that they not only have a reduced sugar metabolism, both also have problems in increasing their fat metabolism during exercise to fully compensate for the energy deficiency. Studies on Triheptanoin diet used in patients with other metabolic diseases have shown that Triheptanoin can increase metabolism of both fat and sugar. In these patients, Triheptanoin has had a positive effect on the physical performance and has reduces the level of symptoms experienced by patients. Aim: To investigate the effect of treatment with the dietary oil, Triheptanoin, in patients with McArdle disease on exercise capacity. Methods: 20-30 adult patients will be recruited through Rigshospitalet in Copenhagen, Denmark, Hopital Pitié-Sapêtrière in Paris, France and through The University of Texas Southwestern Medical Center in Dallas, Texas. Pre-experimental testing (1 day): Baseline blood samples are collected to obtain baseline values of safety parameters: Plasma-acylcarnitines, free fatty acids and creatine kinase. Subjects perform a max-test to determine their VO2max Treatment period #1 (2 weeks): Subjects follow a diet consuming a dietary treatment oil. Neither patients nor members of the study group know who receive which type of oil. Washout period (1 week): Subjects receive no treatment Treatment period #2 (2 weeks): Subjects who received Triheptanoin oil in the first treatment period, now receive placebo oil and vice versa. Assessments: Before and after each treatment periods, subjects perform a 30-minutes exercise test on a cycle ergometer, comprising of 20-22 minutes of constant load exercise and 6-8 minutes increasing load to peak. Subjects will complete a Fatigue Severity Scale questionnaire and metabolic products will be measured in blood and urine.

The purpose of this study is to assess REN001 safety in subjects with McArdle Disease

McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle. Investigators hypothesize that a modified ketogenic diet could be a potential treatment option, by providing ketones as alternative fuel substrates for working muscle. This blinded, placebo-controlled, cross-over study will investigate the potential effects of an optimal modified ketogenic diet found in part A (75% fat, 15%protein, 10%carbohydrates) in patients with McArdle disease compared with a healthy balanced placebo diet (>100grams of carbohydrates per day).

McArdle disease is a metabolic myopathy characterised by the absence of glycogen phosphorylase in skeletal muscle. Sodium Valproate is part of a group of drugs known as histone deacetylase inhibitors, which have a direct effect on chromatin. Recently a drug trial in an animal model of McArdle disease showed that sodium valproate stimulated the expression of a different isoform of the missing enzyme in skeletal muscle. A safety and feasibility study of sodium valproate in people with McArdle disease has been carried out in London (UK) and Copenhagen (DK) since January 2015. Participants will receive 20mg/Kg/day of sodium valproate for 6 months. The primary outcome measure is exercise performance assessed by cycle ergometry. Pre and post-treatment skeletal muscle biopsies will be performed to assess for glycogen phosphorylase. Together with blood analyses for safety. Additional functional exercise tests will be performed.

McArdle's disease or Glycogen storage disease type 5 (GSD5), the most common muscle glycogenosis, is a rare disabling condition with no effective treatment. There are indications that a special dietary regimen could positively influence the disease manifestations. After contradictory indications for protein rich vs carbohydrate rich diets, several preliminary studies and more and more patients own experiences are now pointing to a low carbohydrate ketogenic diet (LCKD) as possibly effective in improving exercise tolerance and reducing muscle damage. The investigators propose a multicentre randomized single blind controlled trial testing efficacy of an individualized LCKD in GSD5. The investigators will test the ability of a 6 months dietary regimen with a 3:1 LCKD inducing a BOHB blood concentration of 1.5-4 mmol/l to improve the aerobic capacity as measured by peak VO2 at exercise testing in GSD5 patients. Thirty molecularly defined MCA adults will be enrolled: to half of them randomly selected the dietary regimen will be prescribed, while subjects in the control group will follow their usual balanced diet. The evaluators will be blinded to the diet followed by the examined patient

McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle. Investigators hypothesize that ketones can be an alternative fuel substrate for skeletal muscle when muscle glycogenolysis is blocked as in McArdle disease. In this study investigators will investigate the immediate effects of an oral supplementation of exogenous ketone bodies (poly-hydroxybuturate) on exercise capacity in patients with metabolic myopathies, compared with a placebo drink.

Background: Patients with the sugar metabolism disorder, Glycogen Storage Disease Type V, have insufficient breakdown of sugar stored as, glycogen, within the cells. The investigators know from previous studies with McArdle patients, that they not only have a reduced sugar metabolism, both also have problems in increasing their fat metabolism during exercise to fully compensate for the energy deficiency. Studies on Triheptanoin diet used in patients with other metabolic diseases have shown that Triheptanoin can increase metabolism of both fat and sugar. In these patients, Triheptanoin has had a positive effect on the physical performance and has reduces the level of symptoms experienced by patients. Aim: To investigate the effect of treatment with the dietary oil, Triheptanoin, in patients with McArdle disease on exercise capacity. Methods: 20-30 adult patients will be recruited through Rigshospitalet in Copenhagen, Denmark and Hopital Pitié-Sapêtrière in Paris, France. Pre-experimental testing (1 day): Baseline blood samples are collected to obtain baseline values of safety parameters: Plasma-acylcarnitines, free fatty acids and creatine kinase. Subjects perform a max-test to determine their VO2max Treatment period #1 (2 weeks): Subjects follow a diet consuming a dietary treatment oil. Neither patients nor members of the study group know who receive which type of oil. Washout period (1 week +7 days): Subjects receive no treatment Treatment period #2 (2 weeks +7days): Subjects who received Triheptanoin oil in the first treatment period, now receive placebo oil and vice versa. Assessments: Before and after each treatment periods, subjects perform a 30-minutes exercise test on a cycle ergometer, comprising of 20-22 minutes of constant load exercise and 6-8 minutes increasing load to peak. Subjects will complete a Fatigue Severity Scale questionnaire and metabolic products will be measured in blood and urine.