Condition category
Nervous System Diseases
Date applied
22/04/2008
Date assigned
09/06/2008
Last edited
04/07/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Mary Reilly

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CMT-TRAUK 2

Study information

Scientific title

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

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).

Study design

Phase III prospective, randomised, double-blind, placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

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

Phase

Not Specified

Drug names

Ascorbic acid

Primary outcome measures

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 trial start date

01/03/2007

Overall trial end date

01/08/2009

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

50: 25 active treatment; 25 placebo

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

United Kingdom

Trial participating centre

MRC Centre for Neuromuscular Disease and Department of Molecular Neurosciences
London
WC1N 3BG
United Kingdom

Sponsor information

Organisation

University College London (UCL) and University College London Hospitals NHS Trust (UCLH) (UK)

Sponsor details

Joint UCLH & UCL Biomedical Resaerch Unit
Rosenheim Wing
Ground floor
25 Grafton Way
London
WC1E 5DB
United Kingdom
y.enever@ucl.ac.uk

Sponsor type

Government

Website

http://www.uclh.nhs.uk/

Funders

Funder type

Charity

Funder name

Muscular Dystrophy Campaign (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21393063

Publication citations

  1. Results

    Pareyson D, Reilly MM, Schenone A, Fabrizi GM, Cavallaro T, Santoro L, Vita G, Quattrone A, Padua L, Gemignani F, Visioli F, Laurà M, Radice D, Calabrese D, Hughes RA, Solari A, , , Ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial., Lancet Neurol, 2011, 10, 4, 320-328, doi: 10.1016/S1474-4422(11)70025-4.

Additional files

Editorial Notes