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Modified Ketogenic Diet in Patients With McArdle Disease Part A

Not Applicable
Completed
Conditions
McArdle Disease
Interventions
Other: Modified ketogenic diets
Registration Number
NCT03843606
Lead Sponsor
Rigshospitalet, Denmark
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%.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
11
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.).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
diet 3Modified ketogenic diets80% fat, 15% protein, 5% carbohydrates
diet 1Modified ketogenic diets60% fat, 15% protein, 25% carbohydrates
diet 2Modified ketogenic diets70% fat, 15% protein, 15% carbohydrates
Primary Outcome Measures
NameTimeMethod
Heart rate2 times

heart rate during constant load cycling exercise

Secondary Outcome Measures
NameTimeMethod
Perceived exertion2 times

Borg scale during constant load cycling

Compliance3 weeks

Dietary diary to evaluate compliance and diet acceptability

indirect calorimetry2 times

Oxidation rates measured via indirect calorimetry during constant load cycling calorimetry

other blood samples2 times

Cholesterol, fatty acids, hormones, ammonia

level of ketosisdaily

Ketone bodies in the blood

Safety parameters2 times

Blood samples

Trial Locations

Locations (1)

Copenhagen Neuromuscular Center, Rigshospitalet

🇩🇰

Copenhagen, Denmark

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