Modified Ketogenic Diet in Patients With McArdle Disease Part A

Rigshospitalet

Status: Completed

Conditions: McArdle Disease

Treatments: Other: Modified ketogenic diets

Study type: Interventional

Funder types: Other

Identifiers

NCT03843606

H-18013022

Details and patient eligibility

About

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.

Full 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%.

Enrollment: 11 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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11 participants in 3 patient groups

diet 1

Experimental group

Description:

60% fat, 15% protein, 25% carbohydrates

Treatment:

Other: Modified ketogenic diets

diet 2

Experimental group

Description:

70% fat, 15% protein, 15% carbohydrates

Treatment:

Other: Modified ketogenic diets

diet 3

Experimental group

Description:

80% fat, 15% protein, 5% carbohydrates

Treatment:

Other: Modified ketogenic diets