Clinical Trial Results:
A Phase II pilot study to explore treatment with Sodium Valproate in Adults with McArdle Disease (Glycogen Storage Disorder Type V, GSDV)
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Summary
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EudraCT number |
2012-002933-12 |
Trial protocol |
GB |
Global end of trial date |
10 Dec 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Mar 2019
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First version publication date |
14 Mar 2019
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Other versions |
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Summary report(s) |
Valproate for McArdle disease |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
11/0090
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
University College London
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Sponsor organisation address |
149, tottenham Court Road, London, United Kingdom, W1T 7NF
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Public contact |
Dr Ros Quinlivan, MRC Centre for Neuromuscular Disease, National hospital for neurology and Neurosurgery, 0203 4488132, r.quinlivan@ucl.ac.uk
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Scientific contact |
Dr Ros Quinlivan, MRC Centre for Neuromuscular Disease, National hospital for neurology and Neurosurgery, 0203 4488132, r.quinlivan@ucl.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Dec 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Dec 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Dec 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
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.
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Protection of trial subjects |
An independent data monitoring committee was not deemed necessary by the sponsor. Measures to protect patients included avoidance of pre-treatment muscle biopsy if the patient had previously had one. Regular trial monitoring on the part of the sponsor. Rapid notification of SAE. All subjects were given emergency contact details of the CI and investigator and regular telephone contact with the subjects was maintained during the trial between trial visits.
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Background therapy |
There was no background therapy. | ||
Evidence for comparator |
This was an open label study, there were no comparators. | ||
Actual start date of recruitment |
01 Mar 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
8
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
8
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
49 people were contacted to take part in this clinical trial. All were attending a 'highly specialized service for McArdle disease and related disorders at the National Hospital for Neurology and Neurosurgery, Queen Square, London. | ||||||||
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Pre-assignment
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Screening details |
11 patients were screened, 2 were not eligible and one dropped out before visit 1. 8 subjects completed the study, 5 male and 3 female. Age mean 46.2 yrs (range 35-59 yrs, SD 8.4) | ||||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||
Blinding implementation details |
This was an open label study, there was no blinding
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Arms
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Arm title
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treatment | ||||||||
Arm description |
there was only one arm as this was an open label study | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
Sodium Valproate
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Investigational medicinal product code |
VPA
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Modified release VPA was prescribed at a treatment dose of 20mg/kg/day. The dose was rounded up or down to the nearest value dependent on weight.
VPA dose was titrated over 4 weeks from a starting dose of 5mg/kg/day to the treatment dose of 20mg/kg/day in order to minimise side effects.
At the end of the study VPA was titrated down over 4 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
treatment group
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
all trial participants received treatment
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End points reporting groups
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Reporting group title |
treatment
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Reporting group description |
there was only one arm as this was an open label study | ||
Subject analysis set title |
treatment group
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
all trial participants received treatment
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End point title |
Workload [1] | ||||||||
End point description |
All participants cycled on a cycle ergometer. Oxygen consumption was assessed by a face mask attached to the Cortex ergospirometry (Cortex Metalyzer II, Cortex Biophysik GmbH, Leipzig, Germany) in the UK or Quark CPET (Cosmed Srl., Milan, Italy) in DK. An incremental cycle ergometer test was performed during the screening visit (from zero to 20W in the first minute, increased by at least 5W every two minutes) to determine each participant’s aerobic power (VO2peak). Heart rate (HR), monitored throughout using a 3-lead cardiac monitor, and rate of perceived exertion (RPE) were recorded every minute.
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End point type |
Primary
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End point timeframe |
baseline-28 weeks
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the small sample size, statistical analysis was descriptive only. A statistical report has been attached |
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| No statistical analyses for this end point | |||||||||
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End point title |
Muscle biopsy | ||||||||||
End point description |
The number of muscle fibres staining positively for glycogen phosphorylase was recorded at baseline (pre-treatment muscle biopsy) and after 28 weeks (post-treatment muscle biopsy
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End point type |
Secondary
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End point timeframe |
Baseline and 28 weeks
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| No statistical analyses for this end point | |||||||||||
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End point title |
forearm exercise test | ||||||||
End point description |
This test consisted of repetitive maximal handgrip contractions every other second for one minute (30 contractions) followed by 5min rest. Plasma lactate was analysed at 0, 2 and 5 minutes following the exercise.
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End point type |
Secondary
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End point timeframe |
baseline, 16 weeks and 28 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
12 minute walk test | ||||||
End point description |
A 12MWT was performed after 45 minutes of rest, following the cycle ergometer test. Participants were requested to complete as many 10m shuttle walks as possible for 12 minutes on a marked corridor.20 The total walked distance was recorded.
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End point type |
Secondary
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End point timeframe |
baseline, 16 weeks and 28 weeks
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| No statistical analyses for this end point | |||||||
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End point title |
SF36, physical functioning | ||||||
End point description |
All subjects completed an SF36 questionnaire
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End point type |
Secondary
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End point timeframe |
change from baseline, 16 weeks and 28 weeks
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events events were documented at week 16 and 28. SAE were reported within 24 hours
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Adverse event reporting additional description |
Adverse events were assessed as either not IMP related, possibly IMP related or probably IMP related
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
all patients
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Reporting group description |
All patients were enrolled into this open lable trial. Adverse events were reported for all 8 patients treated with the IMP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| This was a small open label study, statistical analysis was descriptive only | |||
