Randomised, double blind, placebo-controlled, trial of long-term ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A

ISRCTN	ISRCTN61074476
DOI	https://doi.org/10.1186/ISRCTN61074476
Secondary identifying numbers	CMT-TRAUK 2

Submission date: 22/04/2008
Registration date: 09/06/2008
Last edited: 04/07/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Dr Mary Reilly
Scientific

MRC Centre for Neuromuscular Disease and Department of Molecular Neurosciences
National Hospital for Neurology and Neurosurgery and Institute of Neurology
Queen Square
London
WC1N 3BG
United Kingdom

Phone	+44 (0)20 7837 3611 ext. 3457
Email	m.reilly@ion.ucl.ac.uk

Study information

Study design	Phase III prospective, randomised, double-blind, placebo-controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title
Study acronym	CMT-TRAUK
Study hypothesis	To assess the efficacy and safety of chronic treatment with ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT1A). To date there is no pharmacological treatment for CMT1A patients. Recently, treatment with ascorbic acid (AA) has been shown to be effective for transgenic mice overexpressing PMP22, a model of the human disease.
Ethics approval(s)	Ethics approval received from the National Hospital for Neurology and Neurosurgery Ethics Committee and the Institute of Neurology Joint Research Ethics Committee (REC) on the 6th October 2006 (ref: 06/Q0512/88).
Condition	Charcot-Marie-Tooth disease type 1A (CMT1A)
Intervention	The AA treated group received chronic therapy with ascorbic acid 1500 mg/day divided in morning (500 mg tablets) and evening (two 500 mg tablets) doses for a period of two years. The same dose regimen was prescribed for the group randomised to the placebo. Total duration of follow-up for all treatment arms: 2 years.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Ascorbic acid
Primary outcome measure	Improvement of 0.5 or more in the Charcot-Marie-Tooth neuropathy score (CMTNS) in participants treated with AA versus 1 point worsening in the placebo group at 24 months since enrolment.
Secondary outcome measures	Changes in: 1. Distal arm and leg strength (measured by maximum voluntary isometric contraction), performed every 6 months (baseline, 6, 12, 18 and 24 months) 2. 10-metre time walking, performed every 6 months (baseline, 6, 12, 18 and 24 months) 3. Nine-hole-peg test, performed every 6 months (baseline, 6, 12, 18 and 24 months) 4. Overal Neuropathy Limitation Scale, performed every 6 months (baseline, 6, 12, 18 and 24 months) 5. Visual Analogue Scale (VAS) for pain and fatigue, performed at baseline, 12 and 24-month visits 6. Health-related quality of life (assessed with the 36-item Short Form [SF-36] health survey), performed at baseline, 12 and 24-month visits 7. Electrophysiological parameters, performed every 6 months (baseline, 6, 12, 18 and 24 months) 8. Assessment of small fibre function with thermal thresholds, contact heat evoked potentials (CHEPs) and pain questionnaires are performed at baseline visit and 24-month visit
Overall study start date	01/03/2007
Overall study end date	01/08/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	50: 25 active treatment; 25 placebo
Participant inclusion criteria	1. Clinical diagnosis of CMT1A 2. Genetic confirmation of CMT1A, based on presence of 17p11.2 duplication 3. CMT neuropathy score (CMTNS) between 1 (excluding the electrophysiological component) and 35 (including the electrophysiological component) 4. Aged 18 - 70 years, either sex 5. Ability to accomplish the primary outcome measures 6. Women of child-bearing age only if not pregnant or breast feeding 7. Signed informed consent
Participant exclusion criteria	1. Clinical or echographic diagnosis of nephrolithiasis 2. Positive history of recurrent renal colic 3. One or more episodes of renal colic during the six months prior to enrolment 4. Deficit of glucose-6P-dehydrogenase (G6PD) (non-spherocytic haemolytic anaemia due to G6PD deficiency) 5. Acquired or hereditary haemochromatosis; thalassemia major; sideroblastic anaemia 6. Treatment with ramified chain amino-acids or other drugs considered as potential therapeutic agents for CMT1A during the three months prior to screening 7. AA treatment in the three months prior to screening 8. Other causes of neuropathy (e.g. diabetes, monoclonal gammopathy, cryoglobulinaemia, neoplasms, vitamin B12 deficiency, hepatitis C virus [HCV]-related liver disease) 9. Presence of other neurological disorder (such as multiple sclerosis, cerebrovascular diseases, movement disorders), or major comorbidities (e.g., definite cognitive impairment, psychiatric disease, heart or lung failure, orthopaedic or rheumatological disorders) 10. Limb surgery during the six months prior to screening (or planned before final assessment)
Recruitment start date	01/03/2007
Recruitment end date	01/08/2009

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

MRC Centre for Neuromuscular Disease and Department of Molecular Neurosciences

London
WC1N 3BG
United Kingdom

Sponsor information

University College London (UCL) and University College London Hospitals NHS Trust (UCLH) (UK)
Hospital/treatment centre

Joint UCLH & UCL Biomedical Resaerch Unit
Rosenheim Wing
Ground floor
25 Grafton Way
London
WC1E 5DB
England
United Kingdom

Email	y.enever@ucl.ac.uk
Website	http://www.uclh.nhs.uk/
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Charity

Muscular Dystrophy Campaign (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/04/2011		Yes	No