McArdle disease (Glycogen storage disorder type V) MedDRA version: 17.0 Level: LLT Classification code 10026969 Term: McArdle's disease System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Deprakine
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: SODIUM VALPROATE
CAS Number: 1069-66-5
Concentration unit: mg milligram(s)
Concentration type: range
Concentrat
Sponsors
John Vissing
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects diagnosed with McArdle's disease. Diagnosis will have been confirmed by either muscle biopsy showing subsarcolemmal blebs of glycogen with complete absence of skeletal muscle glycogen phosphorylase and/or DNA studies showing pathogenic homozygous or compound heterozygous mutations or deletions in the muscle phophorylase gene. 2. Subjects over 18 years of age 3. Normal serum carnitine and acylcarnitine blood profiles at screening visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Children under the age of 18 years 2. Pregnant women 3. Known Diabetes mellitus 4. Inflammatory disorders especially systemic lupus erythematosis. 5. A previous history of sensitivity/allergy to sodium valproate. 6. Patients treated with sodium valproate for epilepsy or a psychiatric disorder within the last 12 months prior to recruitment. 7. Patients with pre-existing liver disease or a family history of severe liver disease affecting a first degree relative. Patients with GSDV may have raised serum transaminases that originate from muscle but which may cause abnormal liver function tests measured in serum, this will not be a reason for exclusion. Patients with mild elevation in bilirubin caused by clinically insignificant Gilbert’s syndrome (as demonstrated by a high ratio of unconjugated/conjugated billirubin) will also be included in the study. 8. Patients prescribed other anti-convulsant medication or any other medication known to interact with sodium valproate. 9. Patients who are sensitive to local anaesthetics that would prevent muscle biopsy. 10. Subjects with any co-morbid illness or disability which would prevent an exercise assessment such as severe unstable/ untreated ischaemic heart disease, lower limb disability such as severe muscle weakness with muscle strength assessed as worse than MRC scale 3 in any pelvic girdle muscle. 11. Inability to exercise due to a lower limb fracture would be an exclusion criterion until there is complete recovery of the injury. 12. Patients known to have porphyria or an affected first degree relative affected with porphyria will be excluded from the study. 13. Patients known to have mitochondrial disease or where there is a first degree relative with mitochondrial disease. 14. Patients with a history of abnormal acyl carnitine profile or low serum carnitine level
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate, if administration of sodium valproate in patients with McArdle's disease improves exercise capacity, as measured during a cycle ergometer test, and to test feasibility of a larger scale study.;Secondary Objective: To investigate, if administration of sodium valproate induces expression of an alternative isoform of myophoshporylase in muscles of patients with McArdle's disease, as seen in histochemically stained muscle biopsies.;Primary end point(s): The primary outcome measure will be exercise endurance, measured on a cycle ergometer. Primary outcome measures will include changes in mean estimate and standard deviation from baseline to 6 months on full treatment in: • Workload measured in watts. • Maximum heart rate. • Oxygen consumption to calculate the respiratory quotient (RQ). • Rating of perceived exertion (RPE) during exercise. Before exercise an intravenous cannula/ butterfly will be inserted so that blood samples can be obtained for three laboratory measures of exercise endurance: glucose, ammonia and lactate. Samples will be drawn at rest t=0, 5, 10, 15 and 20 minutes or at exhaustion.;Timepoint(s) of evaluation of this end point: After 6 months on full dose treatment (approximately 8 months after onset of treatment). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: After 6 months on full dose treatment (approximately 8 months after onset of treatment).;Secondary end point(s): 1. Changes in number of muscle fibers that stain positively for muscle glycogen phosphorylase and total phosphorylase content, from before treatment to 6 months on full dose treatment. Muscle biopsies taken from the upper or lower limb will be performed before treatment and from the same muscle on the contralateral side after 7-8 months of treatment, after the final exercise assessment, while still under full dose sodium valproate treatment. 2. Changes in performance in a 12-minute walk test at 0, 4 and 7 months. Outcome measures will include maximum heart rate and total distance walked. 3. The ability to produce lactic acid, in working muscles, during a 1 minute forearm exercise test. 4. SF36 scores and assessment of symptom diary for frequency of muscle cramps and myoglobinuria. 5. Laboratory serum parameters for safety and compliance including: creatine kinase (CK), blood trough serum levels of sodium valproate, full blood count, liver function, ammonia and renal function. | — |
Countries
Denmark
Contacts
Public ContactNeuromuscular research unit
Neuromuscular research unit, Rigshospitalet
Outcome results
None listed