McArdle Disease
Conditions
Brief summary
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.
Detailed description
Open interventional study to investigate 3 different modified ketogenic diet regimes, to find an optimal composition of a modified ketogenic diet for patients with McArdle disease McArdle disease, glycogen storage disease type V, is a rare metabolic disease caused by mutations in the PYGM gene resulting in absence of the enzyme muscle phosphorylase. Affected individuals are unable to utilize sugar stored as glycogen in muscle, leading to exercise intolerance, exercise-induced muscle pain, contractures and rhabdomyolysis, which may cause renal failure. Currently, there are no satisfactory treatment options for McArdle disease. Ketones are feasible fuel alternatives to muscle glycogen when muscle glycogenolysis is blocked as in McArdle disease. A key element of alleviating symptoms in McArdle disease is to provide alternative fuels for energy metabolism. Ketosis can potentially provide alternative fuel substrates by provision of endogenous ketone bodies (KBs) which are desirable fuels for skeletal muscle and brain. Ketosis can be reached by fasting and can be induced by adhering to a modified ketogenic diet, which entails a high-fat, low-carbohydrate diet, which simulates the metabolic effects of fasting. The optimal modified ketogenic diet composition, that ensures adequate degree of ketosis and at the same time is well tolerated, has not been investigated in patients with McArdle disease. Therefore this pilot study seeks to investigate which of 3 different diets is the most optimal ad effective for patients with McArdle disease. The 3 different diets will have carbohydrate percentages ranging from 5-25%, and fat percentage from 60-80%.
Interventions
OTHERModified ketogenic diets
Different diet composition
Sponsors
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open interventional study to investigate the effects of 3 different ketogenic diet regimes
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Genetically confirmed GSDV * Patient is willing and able to provide written informed consent prior to participation. * Patient is ambulatory. * Women in fertile age must be willing to practice the following medically acceptable methods of birth control
Exclusion criteria
* Patient has any prior or current medical conditions that, in the judgment of the Investigator, would prevent the patient from safely participating in and/or completing all study requirements. * Pregnancy or breastfeeding * Patient does not have the cognitive capacity to understand/comprehend and complete all study assessments * Patients with porphyria or disorders of fat metabolism (primary carnitine deficiency, carnitine palmitoyltransferase I or II, β-oxidation defects etc.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heart rate | 2 times | heart rate during constant load cycling exercise |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| indirect calorimetry | 2 times | Oxidation rates measured via indirect calorimetry during constant load cycling calorimetry |
| level of ketosis | daily | Ketone bodies in the blood |
| Compliance | 3 weeks | Dietary diary to evaluate compliance and diet acceptability |
| Perceived exertion | 2 times | Borg scale during constant load cycling |
| other blood samples | 2 times | Cholesterol, fatty acids, hormones, ammonia |
| Safety parameters | 2 times | Blood samples |
Countries
Denmark
Outcome results
None listed