First clinical trial for Charcot-Marie-Tooth disease

Dr Reilly and her colleagues ran this first clinical trial for Charcot-Marie-Tooth Disease type 1A to see if vitamin C could slow the progression of the disease.
Dr Reilly and her colleagues ran this first clinical trial for Charcot-Marie-Tooth Disease type 1A to see if vitamin C could slow the progression of the disease.


What were the researchers aiming to do?

In 2004, researchers discovered that when they gave vitamin C to a mouse model of CMT1A, there was an improvement in the symptoms the mice were displaying. These mice also performed better in a series of muscle function tests than untreated mice. Since vitamin C is already freely available there was concern that some people with CMT1A were taking high doses of vitamin C, having read about this study, without there being clear evidence of a similar effect in humans. It was, therefore, decided that a trial should be set up to test if vitamin C did indeed have a similar effect in humans and whether it was safe for this group of individuals to be taking high dose vitamin C.


Dr Reilly and her colleagues in Italy set up this trial to test the safety and efficacy of vitamin C in CMT1A. The trial was a randomized, double-blind, placebo-controlled trial. This means that participants were randomly assigned to receive either vitamin C or a placebo (an inactive substance that looks and tastes just like vitamin C) and neither the doctors nor the participants knew who was getting what. As this was the first trial for CMT it was very important to think carefully about what to measure in order to correctly establish if there was a difference between the people treated with Vitamin C and those who got the placebo – these are called outcome measures. Prior to the trial starting, a European Neuromuscular Centre funded workshop was organised to determine the best outcome measures. The workshop was attended by an international group of clinicians and importantly also included two patient representatives.


Following the workshop it was decided to run the trial in the UK and Italy with the aim of recruiting 272 participants. The participants, aged between 18 and 70 years of age, would get three doses of either Vitamin C (1.5 g in total per day) or the placebo every day for 2 years.  They were followed up every 6 months and measurements such as muscle strength, changes in feeling, walking speed and levels of pain and fatigue assessed. 50 participants were to be recruited in the UK arm of the study, run by Dr Reilly.



What did their research show?

Of the original 50 participants, 38 completed the trial. The 12 who did not complete the trial dropped out for a variety of reasons including adverse events, pregnancy, admissions for surgery, withdrawal of consent and failure to attend follow-up appointments. Unfortunately the trial showed that while the high doses of vitamin C were safe, it did not improve the symptoms nor did it slow the progression of CMT1A on objective tests. Although this is a negative result, it was still important to carry out the trial to prove one way or the other whether vitamin C would have an effect. Researchers will be able to use this information and move onto exploring other avenues for possible therapy.



One important result of this trial has been the validation of the outcome measures for CMT. The fact that this has been a long term trial (2 years) has also allowed Dr Reilly and her colleagues to gather detailed information about how this condition progresses and changes over time. This valuable information will help with the planning of future clinical trials for CMT.

How will the outcomes of the research benefit patients?

This trial has shown that vitamin C does not improve the symptoms or slow the progression of CMT1A. As many people were taking high doses of vitamin C having heard about the animal study, it was important to determine if this might indeed prove to be an effective treatment or whether people were unnecessarily taking this substance.

The work done in this trial also will help to inform and improve future trials for CMT.



Background Information

CMT is the most prevalent inherited neuromuscular condition affecting around 23,000 people in the UK. CMT1A is the commonest form of CMT and is caused by the presence of an extra copy of a gene that carries the instructions for a protein called peripheral myelin protein 22 (PMP-22). PMP-22 has an important role in the formation and maintenance of myelin. Myelin is the layer wrapped around the axon of nerve cells and it is important for the conduction of electrical signals down the nerve. It is thought that having an extra copy of the PMP-22 gene may impair the function of the myelin and thus affecting how well the nerves are able to conduct the electrical signals.



Grant Information


Project Leader: Dr Mary Reilly

Location: MRC Centre for Neuromuscular Diseases, Department of Molecular Neuroscience, UCL  Institute of Neurology

Condition: Charcot-Marie-Tooth disease 1A

Duration: 3 years, completed August 2009

Total Project Cost: £201,601

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



Further information and links

Read more about Dr Reilly’s other Muscular Dystrophy Campaign funded research grant 

Find out the latest research and clinical trial news


Call to action


It is only through your contributions that we can continue to fund the vital work that takes us closer to finding treatments and cures for muscle disease. Donate now and help change the lives of thousands of people living with muscle disease. Thank you for your support.