Charcot-Marie-Tooth disease type 1A (CMT1A) Nervous System Diseases Hereditary and idiopathic neuropathy
Conditions
Interventions
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 regime
Sponsors
University College London (UCL) and University College London Hospitals NHS Trust (UCLH) (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
United Kingdom
Outcome results
None listed