Muscle MRI in Charcot Mary Tooth Disease: a Prospective Cohort Study
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|ClinicalTrials.gov Identifier: NCT03550300|
Recruitment Status : Recruiting
First Posted : June 8, 2018
Last Update Posted : October 4, 2018
|Condition or disease|
|Charcot-Marie-Tooth Disease, Type IA Charcot-Marie-Tooth Disease Type 2A Charcot-Marie-Tooth Disease, Type IB Charcot-Marie-Tooth Disease, Type X|
In this proposed study we will use magnetic resonance imaging (MRI) of skeletal muscle to better delineate the natural history of intramuscular fat accumulation in Charcot Marie Tooth disease (CMT ) and investigate the use of muscle MRI and plasma neurofilament light chain (NEFL) levels as outcome measures in children and adults with specific subtypes of CMT (CMT1A, CMT1B, CMT2A and CMTX1).
We will ascertain the value of MRI-determined fat accumulation in foot, calf and thigh muscles as an independent outcome measure, by analysing its correlation with validated clinical measures [CMT Paediatric Score (CMTPedS) and/or CMT Examination Score version 2 - Rasch (CMTESv2-R)] and sensitivity to change over time compared to matched controls. We will also ascertain the utility of plasma NEFL levels as an independent outcome measure and a potential predictive biomarker of muscle fat accumulation over 12 months.
Following this trial, easily implemented outcome measures will be immediately available for clinical trials seeking to evaluate novel therapies in CMT and data from this trial will also be available to establish sample size for future clinical trials.
This study (participants with CMT and control participants) has two parts (Part 1: CMT1A cohort; Part2: CMT1B, CMT2A and CMTX1 cohort) and is proposed to take place over 3 years across three sites. Participants with CMT aged 5-60 for potential enrolment in the trial will be identified through the existing inherited neuropathy clinics at each site and control participants will be identified among the unaffected relatives and carers of the participants with CMT.
Approximately half of the participants will be recruited at the UK sites (NHNN and GOSH) and the other half at the US collaborating centre (University of IOWA). Each research visit is expected to last approximately 3 hours and during it, relevant detailed clinical data will be collected (CMTPedS for participants with CMT aged 5-20, CMTESv2-R for participants with CMT over the age of 10, CMT-HI for participants with CMT over the age of 16) and the participant will also undergo an MRI scan (up to 45 minutes) of the lower limbs (feet and calves or calves and thighs). Two separate neuromuscular MRI protocols with specific sequences will be used for the scans of foot and calf muscles and scans of calf and thigh muscles. Blood samples for plasma NEFL levels will be optional at both research visits for the participants at the UK trial sites; plasma NEFL levels will be processed according to our previously published protocol.
The primary objective is to define the responsiveness of MRI-determined fat accumulation in foot and calf muscles (in children/young adults aged 5-20 with CMT1A) or calf and thigh muscles (in adults aged 16-60 with CMT1B, CMT2A and CMTX1) over 12 months.
The secondary objectives are a) to assess the validity of MRI-determined muscle fat accumulation as a biomarker by correlating it with validated clinical scores (CMTPedS and/or CMTESv2-R), b) investigate the responsiveness of plasma NEFL in patients with CMT compared to matched controls over 12 months, and c) to investigate the utility of multi-level T2-weighted STIR (short T1 inversion recovery) and plasma NEFL levels as potential predictive biomarkers of muscle fat accumulation over the subsequent 12 months.
|Study Type :||Observational|
|Estimated Enrollment :||130 participants|
|Official Title:||Muscle MRI in Charcot Mary Tooth Disease: a Prospective Cohort Study|
|Actual Study Start Date :||September 11, 2018|
|Estimated Primary Completion Date :||July 1, 2021|
|Estimated Study Completion Date :||October 1, 2021|
Participants with CMT
Participants with CMT1A, CMT1B, CMT2A or CMTX1
- MRI Change in fat accumulation in CMT1A [ Time Frame: 12 months ]Part 1: Statistically significant (p<0.05) change of MRI-determined fat accumulation in foot and calf muscles in children/young adults with CMT1A over 12 months compared to matched controls.
- MRI Change in fat accumulation in CMT1B; CMT2A and CMTX1 [ Time Frame: 12 months ]Part 2: Statistically significant (p<0.05) change of MRI-determined fat accumulation in calf and thigh muscles in adults with CMT1B and CMT2A and male adults with CMTX1 over 12 months compared to matched controls.
- MRI changes validation - CMTPedS [ Time Frame: 12 months ]Validating the change in MRI-determined fat accumulation in foot and calf muscles in children/young adults with CMT1A over 12 months by correlating it with the CMTPedS (all children) and the CMTESv2-R (children aged >10).
- MRI changes validation - CMTESv2-R [ Time Frame: 12 months ]Validating the change in MRI-determined fat accumulation in calf and thigh muscles in adults with CMT1B, CMT2A and CMTX1 over 12 months by correlating it with the CMTESv2-R
- NEFL plasma responsiveness [ Time Frame: 12 months ]Defining the responsiveness of plasma NEFL in patients with CMT compared to matched controls over 12 months.
- NEFL plasma (biomarker) [ Time Frame: 12 months ]Establishing the utility of plasma NEFL levels as a predictive biomarker of intramuscular fat accumulation over the subsequent 12 months in children/young adults with CMT1A.
- Multi-level T2-weighted STIR and plasma NEFL levels (biomarker) [ Time Frame: 12 months ]Establishing the utility of multi-level T2-weighted STIR and plasma NEFL levels as predictive biomarkers of intramuscular fat accumulation over the subsequent 12 months in adults with CMT1B, CMT2A and CMTX1
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03550300
|Contact: Carolynne Dohertyfirstname.lastname@example.org|
|Contact: Mariola Skorupinskaemail@example.com|
|Queen Square Centre for Neuromuscular Diseases||Recruiting|
|London, United Kingdom, WC1n3BG|