Muscle MRI in Charcot-Marie-Tooth Disease (CMT)
Research type
Research Study
Full title
Muscle MRI in Charcot Marie Tooth Disease: a Prospective Cohort Study
IRAS ID
240696
Contact name
Mary Reilly
Contact email
Sponsor organisation
University College London
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
A major barrier to clinical trials in Charcot-Marie-Tooth disease (CMT) is that none of the current outcome measures can detect change adequately over a period of 12-24 months. The main aim of this study is to determine if lower limb intramuscular fat accumulation due to denervation in CMT, can be validated as a sensitive, responsive outcome measure which could be used in future clinical trials in children and adults with CMT.
In this study we will measure the responsiveness of MRI-determined intramuscular fat accumulation in the lower limbs of children and adults with CMT and matched control participants over 12 months. In order to validate the MRI findings, we will analyse their correlation with established clinical outcomes over the same timeframe. We will also ascertain the utility of plasma NEFL levels as a potential predictive biomarker of muscle fat accumulation over 12 months.
152 participants (children and adults) will be recruited into the study at the two participating sites in the UK and at the collaborating centre in the USA: 80 participants with CMT and 72 control participants (22 for optimisation scans only).
Each participant will attend 2 study visits, 12 months apart (baseline visit and 1 year follow up visit). Each visit will involve an MRI scan (all participants) and collection of clinical outcomes from the CMT pediatric scale and/or CMTESv2-R (only participants with CMT). A blood test for plasma NEFL levels (optional for paediatric participants) will be taken at each visit.
The study is funded by the Muscular Disease Association (US). All participants will be recruited and scanned at the one of the three centres: The National Hospital for Neurology and Neurosurgery, The University of Iowa Roy and Lucille Carver College of Medicine and Great Ormond Street Hospital for Children.
Lay summary of study results: There were 2 aims of this study. We had previously developed a MRI protocol to measure fat fraction in calf and thigh muscles and had shown that we could accurately measure progression of this over a year in Charcot Marie Tooth disease type 1A (CMT1A) making it the most promising outcome measure for future clinical trials. In this study we studied this MRI outcome measure in the next three commonest forms of CMT ie CMT1X, CMT2A and CMT1B. We have shown that the MRI fat fraction outcome measure was equally responsive in all of these forms of CMT and have published this in 2024 Ann Clin Transl Neurol. 2024 Mar;11(3):607-617. We have also presented this at the Peripheral nerve society in Miami in 2022.
In the second aim we developed a revised MRI fat fraction outcome measure in children from aged 5-21 with CMT1A and included a novel foot protocol as well as calf and thigh. We have also shown that this is responsive over one year and will be a suitable outcome measure to use in children with ACMT. We published this in 2024 Ann Neurol. 2024 Jul;96(1):170-174. We have also presented this at the Peripheral nerve society in Copenhagen in 2023.REC name
London - Queen Square Research Ethics Committee
REC reference
18/LO/1059
Date of REC Opinion
16 Jul 2018
REC opinion
Further Information Favourable Opinion