A Review of Clinical Trial Readiness for CMT


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In this issue of Brain Research, Mike Shy, Mary Reilly and I summarize the current array of outcome measures for clinical trials of treatments in CMT.  The reason why so much attention has been paid to outcome measures in CMT is best illustrated by looking at the large clinical trials of vitamin C in CMT1A conducted almost a decade ago.

The vitamin C trials in CMT1A were undertaken following successful reports in a mouse model of the disease. In these trials, patients were randomly assigned to receive either vitamin C or placebo over one to two years and the disease severity was measured using the best available monitoring tools, including the CMT neuropathy score version 1. At the end of the trial it was discovered that the best monitoring tools were unable to detect a difference between patients with CMT1A receiving Vitamin C or placebo. This trial pointed out the need to develop more sensitive tools to measure changes in disease progression in CMT1A.

Much has been learnt since these trials and a whole new array of CMT specific outcome measures have now been designed for both adults and children.  These include outcome measures based on a patient’s symptoms, examination findings and nerve conduction studies (the CMT neuropathy score), functional outcome measures in which patients are scored for a variety of tasks (e.g. the CMTpeds and the CMT FOM) and quality of life questionnaires.  In addition, progress has been made in technologies that can monitor disease progression. These include MRI scans of muscle which are able to measure the degree of muscle that is no longer supplied by a nerve. Several of these outcome measures are able to detect disease progression over a one-year period which is essential for any clinical trials.

There has been significant progress in CMT clinical trial design since the vitamin C trials with renewed confidence that any new trial would be able to identify an effective treatment.