A Phase II Pilot Study to Assess Safety and Efficacy of Sodium Valproate in Adults with McArdle Disease

Phase 1

• Conditions: 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.; MedDRA version: 16.1 Level: LLT Classification code 10026969 Term: McArdle's disease System Organ Class: 100000004850; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2012-002933-12-GB
• Lead Sponsor: niversity College London,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-04-04
• Study Completion: 2018-12-10
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 8

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified