Modified Ketogenic Diet in Patients With McArdle Disease Part B
Condition: McArdle Disease
MeSH terms: Glycogen Storage Disease Type V
Study type: Interventional

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. 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).
    

Detailed description: 
      A blinded randomized, placebo-controlled, cross-over study to investigate the effects of a
      modified ketogenic diet in 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. 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 study design is a placebo-controlled, blind, cross over design. The study will be carried
      out at two sites: CNMC (Copenhagen), NHNN (London). Subjects will be randomized 1:1 to
      receive either a modified ketogenic diet (75% fat, 15%protein, 10% carbohydrates) or a
      placebo diet (>100grams of carbohydrates per day) first. Subjects will follow the diet for 4
      weeks, followed by 2-4 weeks wash-out, followed by 4 weeks on the opposite diet. During the
      10-12 weeks trial period, subjects will visit the trial site in London on five occasions.
      Effects of the diet will be evaluated by improvement in exercise capacity during submaximal
      exercise test on a cycle ergometer. Subjective improvements will be evaluated by
      questionnaires and a dietary diary.

      If the diet improves exercise capacity, it will provide a safe and cheap treatment option
      that may lead to reduced risk of muscle injury and enhance quality of life in patients with
      McArdle disease.
    

Intervention name(s): Ketocal 4:1 liquid Nutricia (intervention); Fortini multifibre Nutrica (placebo)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Modified ketogenic diet; Placebo diet
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomized, blind, placebo-controlled, cross over study
Masking: Double (Participant, Investigator)
Primary purpose: Treatment