Modified Ketogenic Diet in Patients With McArdle Disease Part A

Modified Ketogenic Diet in Patients With McArdle Disease Part A - a Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: McArdle Disease
• Intervention / Treatment: Other: Modified ketogenic diets

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%.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Copenhagen Neuromuscular Center, Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: diet 1; 60% fat, 15% protein, 25% carbohydrates	Other: Modified ketogenic diets; Different diet composition
Experimental: diet 2; 70% fat, 15% protein, 15% carbohydrates	Other: Modified ketogenic diets; Different diet composition
Experimental: diet 3; 80% fat, 15% protein, 5% carbohydrates	Other: Modified ketogenic diets; Different diet composition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	heart rate during constant load cycling exercise	2 times

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance	Dietary diary to evaluate compliance and diet acceptability	3 weeks
indirect calorimetry	Oxidation rates measured via indirect calorimetry during constant load cycling calorimetry	2 times
level of ketosis	Ketone bodies in the blood	daily
Safety parameters	Blood samples	2 times
Perceived exertion	Borg scale during constant load cycling	2 times
other blood samples	Cholesterol, fatty acids, hormones, ammonia	2 times

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2019
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 8, 2019

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: February 15, 2019
• First Posted (Actual): February 18, 2019

Study Record Updates

• Last Update Posted (Actual): May 10, 2019
• Last Update Submitted That Met QC Criteria: May 9, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Glycogen Storage Disease; Glycogen Storage Disease Type V
• Other Study ID Numbers: H-18013022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No