- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03550300
Muscle MRI in Charcot Mary Tooth Disease: a Prospective Cohort Study
Study Overview
Status
Detailed Description
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
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Carolynne Doherty
- Phone Number: 02076794466
- Email: c.doherty@ucl.ac.uk
Study Contact Backup
- Name: Mariola Skorupinska
- Phone Number: 02031087544
- Email: mariola.skorupinska@nhs.net
Study Locations
-
-
-
London, United Kingdom, WC1n3BG
- Recruiting
- Queen Square Centre for Neuromuscular Diseases
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Inclusion Criteria for participants with CMT
Part 1 inclusion criteria:
- Participants aged 5-20 years with genetically proven CMT1A or with a clinical diagnosis of CMT1A (including neurophysiology) and a genetically confirmed diagnosis of CMT1A in patient or a 1st degree relative.
- Participants must be able to undergo an MRI scan without sedation and complete the CMTESv2-R and/or CMTPedS scores as appropriate.
- Female participants of childbearing potential who are sexually active must agree to use an effective method of contraception from the time consent is signed until the final research visit.
- Female participants of childbearing potential must have a negative urinary pregnancy test prior to every MRI scan. Participants are considered not of childbearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
- Participants and/or their parent(s)/guardian are willing and able to provide written informed consent and/or appropriate assent. Participants must have a good understanding of English language, in order to be able to do this.
Part 2 inclusion criteria:
- Participants aged 16-60 years with genetically proven CMT1B, CMT2A or CMTX1 or with a clinical diagnosis of one of the above three (including neurophysiology) and a genetically confirmed diagnosis in a 1st degree relative.
- Participants with CMTX1 must be male.
- Participants must be able to undergo an MRI scan without sedation and complete the CMTESv2-R score.
- Female participants of childbearing potential who are sexually active must agree to use an effective method of contraception from the time consent is signed until the final research visit.
- Female participants of childbearing potential must have a negative urinary pregnancy test prior to every MRI scan. Participants are considered not of childbearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
- Participants are willing and able to provide written informed consent. Participants must have a good understanding of English language, in order to be able to do this.
Inclusion criteria for control participants
- Participants are aged 5-60 years.
- Participants must be able to undergo an MRI scan without sedation.
- Female participants of childbearing potential who are sexually active must agree to use an effective method of contraception from the time consent is signed until the final research visit.
- Female participants of childbearing potential must have a negative urinary pregnancy test prior to every MRI scan. Participants are considered not of childbearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
- Participants and/or their parent(s)/guardian are willing and able to provide written informed consent and/or appropriate assent. Participants must have a good understanding of English language, in order to be able to do this.
Exclusion Criteria:
Exclusion criteria for participants with CMT
- Participants have undergone foot surgery in the 6 months prior to trial enrollment or are due to undergo foot surgery during the 12 months of the trial.
- Participants have another medical condition which precludes them from having an MRI scan or completing the CMTESv2-R or the CMTPedS scores as appropriate.
- Participants with known diagnosis of another neuromuscular disease.
- Females who are planning pregnancy or breastfeeding
Exclusion criteria for control participants
- Participants with known diagnosis of another neuromuscular disease.
- A risk of developing a neuromuscular condition if the control participant is a relative of a participating patient with CMT.
- Females who are planning pregnancy or breastfeeding
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
---|
Participants with CMT
Participants with CMT1A, CMT1B, CMT2A or CMTX1
|
Control participants
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
12 months
|
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.
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
12 months
|
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
|
12 months
|
NEFL plasma responsiveness
Time Frame: 12 months
|
Defining the responsiveness of plasma NEFL in patients with CMT compared to matched controls over 12 months.
|
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.
|
12 months
|
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
|
12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Neuromuscular Diseases
- Stomatognathic Diseases
- Neurodegenerative Diseases
- Peripheral Nervous System Diseases
- Heredodegenerative Disorders, Nervous System
- Nervous System Malformations
- Polyneuropathies
- Tooth Diseases
- Nerve Compression Syndromes
- Charcot-Marie-Tooth Disease
- Hereditary Sensory and Motor Neuropathy
Other Study ID Numbers
- 18/0244
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Charcot-Marie-Tooth Disease, Type IA
-
Hereditary Neuropathy FoundationRecruitingCharcot-Marie-Tooth Disease | Charcot-Marie-Tooth Disease, Type IA | Charcot-Marie-Tooth Disease Type 2A | Charcot-Marie-Tooth | Charcot-Marie-Tooth Disease, Type IB | Charcot-Marie-Tooth Disease Type 2 | Charcot-Marie-Tooth Disease, Type 2C | Charcot-Marie-Tooth Disease Type 2A2B | Charcot-Marie-Tooth... and other conditionsUnited States
-
University of IowaJohns Hopkins University; University of Colorado, Denver; King's College Hospital... and other collaboratorsRecruitingCharcot-Marie-Tooth Disease, Type Ia (Disorder) | HMSNUnited States, Italy, United Kingdom, Australia
-
Pharnext S.C.A.Premier Research Group plc; Eurofins Optimed; Synteract HCR (Syneos Health); Gr... and other collaboratorsActive, not recruitingCharcot-Marie-Tooth Disease, Type IAUnited States, Belgium, Canada, France, Netherlands, Spain, United Kingdom
-
Wayne State UniversityMuscular Dystrophy Association; Charcot-Marie-Tooth AssociationCompleted
-
University Hospital, Clermont-FerrandCompletedCharcot-Marie-Tooth Type 1A NeuropathyFrance
-
University Hospital, Clermont-FerrandActive, not recruitingCharcot-Marie-Tooth Type 1A NeuropathyFrance
-
Samsung Medical CenterNot yet recruitingCharcot-Marie-Tooth Disease, Type 1
-
Nationwide Children's HospitalSuspendedCharcot-Marie-Tooth Neuropathy Type 1AUnited States
-
Tasly GeneNet Pharmaceuticals Co., LtdRecruitingCharcot-Marie-Tooth Type 1AChina
-
ENCellCompletedCharcot-Marie-Tooth Disease, Type IAKorea, Republic of