McArdle disease (Glycogen storage disease type V, GSDV). The condition is an inherited disorder of skeletal muscle that causes exercise intolerance. The condition can give way to potential rhabdomyolysis which can cause acute renal failure and from middle age muscle wasting and weakness. Affected patients are unable to produce lactate during ischaemic exercise due to a congenital lack of the enzyme muscle glycogen phosphorylase which is essential for glycogen metabolism. MedDR
Conditions
Interventions
Trade Name: Epilim Chrono 200 Controlled Released tablets
Product Name: Epilim Chrono 200 Controlled Released tablets
Pharmaceutical Form: Prolonged-release tablet
Sponsors
University College London,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and infertile/ post menopausal female subjects diagnosed with GSDV and over 18 years of age. Diagnosis will be 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 deletion in the muscle phosphorylase gene (PYGM). 2. Prior to recruitment all subjects will have been shown to have normal serum carnitine level and acylcarnitine blood profile. 3. Patients with mild elevation in bilirubin caused by Gilbert's syndrome will be included following assessment and according to the clinical judgment of the investigator. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 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. People older than 64 years 3. Females of child bearing potential 4. Patients with Diabetes 5. Inflammatory disorders especially Systemic lupus erythematosis. 6. A previous history of sensitivity/allergy to sodium valproate and its excipients 7. Patients treated with sodium valproate for epilepsy or a psychiatric disorder within the last 12 months prior to recruitment 8. Patients with pre-existenig liver disease or a family history of severe liver disease affecting a first degree relative. Liver disease will be defined by abnormal liver biopsy. Patients with GSDV will 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. 9. Patients prescribed other anti-convulsant medication or any other medication known to interact with sodium valproate. 10. Patients who are sensitive to local anaesthetics that would prevent a muscle biopsy. 11. 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. 12. Inability to exercise due to a lower limb fracture until there is a complete recovery of the injury. 13. Patients known to have porphyria or an affected first degree relative affected with porphyria 14. Patients known to have mitochondrial disease or where there is a first degree relative with mitochondrial disease 15. Patients with an abnormal acyl carnitine profile or low serum carnitine levels 16. Male participants unwilling to use contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether patients taking a medicine called sodium valproate can improve muscle function expressed by an increased number of normal muscle fibres on muscle biopsy. ; Secondary Objective: After at least 6 months of full dose treatment, secondary objectives include: 1. Number of muscle fibres expressing Muscle Glycogen Phosphorylase 2. Maximum walking distance in 12 minutes 3. Forearm Exercise test 4. Quality of life measure SF36 and symptom diary 5. Safety including tolerability and adverse events ; Primary end point(s): The primary outcome will be an assessment of exercise endurance on a cycle ergometer by a number of physical and biochemical measures. We will determine changes in the mean estimate and standard deviation of the following parameters: - Rating of perceived exertion (RPE), - Oxygen consumption to calculate the respiratory quotient (RQ) - Maximum heart rate and workload from baseline to 6 months on full dose treatment - Laboratory measures associated with exercise endurance will include blood samples for glucose, lactate and ammonia taken at 0, 5, 10, 15, 20 minutes (or until exhaustion)during exercise. ;Timepoint(s) of evaluation of this end point: We will assess patients at baseline, 4 months and 7 months for primary and secondary outcome measures. There will be monthly telephone contact throughout the trial to assess for adverse events and compliance. There will be a post trial visit three months after the end of the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): After at least 6 months on full dose treatment 1. Number of muscle fibres expressing phosphorylase 2. Maximum walking distance in 12 minutes 3. Forearm exercise test 3. Quality of life measure SF36 and symptom diary 4. Safety including tolerability and adverse events | — |
Countries
Denmark, United Kingdom, United States
Contacts
Public ContactTahera Hussain
MRC Centre for Neuromuscular Diseases
Outcome results
None listed