Sodium Valproate for GSDV

NCT03112889 | Completed Phase 2 DMC

• 1 other identifier: 11/0090
• Study Type: interventional
• Target: 8
• Locations: 2 countries
• Sites: 2

Brief Summary

McArdle disease is a metabolic myopathy characterised by the absence of glycogen phosphorylase in skeletal muscle. Sodium Valproate is part of a group of drugs known as histone deacetylase inhibitors, which have a direct effect on chromatin. Recently a drug trial in an animal model of McArdle disease showed that sodium valproate stimulated the expression of a different isoform of the missing enzyme in skeletal muscle. A safety and feasibility study of sodium valproate in people with McArdle disease has been carried out in London (UK) and Copenhagen (DK) since January 2015. Participants will receive 20mg/Kg/day of sodium valproate for 6 months. The primary outcome measure is exercise performance assessed by cycle ergometry. Pre and post-treatment skeletal muscle biopsies will be performed to assess for glycogen phosphorylase. Together with blood analyses for safety. Additional functional exercise tests will be performed.

Conditions

Glycogen Storage Disease Type V; McArdle Disease

Keywords

McArdle Disease; McArdle's Disease; Glycogen Storage Disease Type V; GSDV; Sodium Valproate; Valproic Acid; Myophosphorylase Deficiency; Muscle Phosphorylase Deficiency; Glycogenosis; Glycogen Storage Disorder

Outcome Measures

Primary Outcomes (1)

• Change in VO2peak

  The aerobic power will be measured at peak workload after a +- 15 minutes incremental cycle test performed on a cycle ergometer after 15 minutes constant load cycling.

  Week 1, Week 16 and Week 28

Secondary Outcomes (6)

• Presence of phosphorylase positive fibres

  Week 0 and Week 28

• Change in total walked distance

  Week 1, Week 16 and Week 28

• Blood lactate responses to exercise

  Week 1, Week 16 and Week 28

• Safety of sodium valproate assessed by blood exams and self-reported adverse events

  For the duration of the trial and within 3 months of Visit 3 (+- Week 40)

• Adverse events log

  Week 4, Week 8, Week 16, Week 20, Week 24, Week 28, +- Week 40

Study Arms (1)

Sodium Valproate

EXPERIMENTAL

Subjects will receive sodium valproate modified release 20mg/kg/day (maximum dose 2.0g/day) administered orally once daily for six months.

Drug: Sodium Valproate

Interventions

Sodium Valproate DRUG

Subjects will receive sodium valproate modified release 20mg/kg/day (maximum dose 2.0g/day) administered orally once daily for six months.

Sodium Valproate

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male subjects and post-menopausal or infertile females
• Diagnosed with GSDV and over 18 years of age
• Normal serum carnitine level and acylcarnitine blood profile at screening visit

You may not qualify if:

• Children under the age of 18 years
• People older than 64 years
• Females of child bearing potential
• Patients with Diabetes
• Inflammatory disorders especially systemic lupus erythematosis.
• A previous history of sensitivity/allergy to sodium valproate and its excipients
• Patients treated with sodium valproate for epilepsy or a psychiatric disorder within the last 12 months prior to screening
• Patients prescribed other anti-convulsant medication or any other medication known to interact with sodium valproate (see section 9.3).
• Patients who are sensitive to local anaesthetics that would prevent muscle biopsy.
• 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.
• Patients known to have porphyria or an affected first degree relative affected with porphyria will be excluded from the study.
• Patients known to have mitochondrial disease or where there is a first degree relative with mitochondrial disease.
• Patients with a history of abnormal acyl carnitine profile or low serum carnitine level
• Male participants unwilling to use contraception

Sponsors & Collaborators

• University College, London: lead

Study Sites (2)

Rigshospitalet

Copenhagen, Denmark

Location

MRC Centre for Neuromuscular Diseases

London, WC1N 3BG, United Kingdom

Location

Related Publications (1)

• Howell JM, Dunton E, Creed KE, Quinlivan R, Sewry C. Investigating sodium valproate as a treatment for McArdle disease in sheep. Neuromuscul Disord. 2015 Feb;25(2):111-9. doi: 10.1016/j.nmd.2014.10.002. Epub 2014 Oct 13.

  PMID: 25455802 BACKGROUND

MeSH Terms

Conditions

Glycogen Storage Disease Type V; Glycogen Storage Disease

Interventions

Valproic Acid

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Ros Quinlivan, FRCPCH, MD

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2015
• First Posted: April 13, 2017
• Study Start: January 1, 2015
• Primary Completion: April 5, 2017
• Study Completion: April 5, 2017
• Last Updated: February 5, 2018

Record last verified: 2018-02

Locations

GB (1); DK (1)