Charcot-Marie-Tooth Disease, Type IANCT03550300
Muscle MRI in Charcot Mary Tooth Disease: a Prospective Cohort Study
An observational study of Charcot-Marie-Tooth Disease, Type IA and Charcot-Marie-Tooth Disease Type 2A, run by University College, London at 1 site in United Kingdom.
Trial summary
This cohort 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. Read more about this study
- Who is it for?
- Ages 5 to 60 years
- Conditions the study is for
- Charcot-Marie-Tooth Disease, Type IA, Charcot-Marie-Tooth Disease Type 2A, Charcot-Marie-Tooth Disease, Type IB
- How many people
- 130 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Sep 2018to 1 Oct 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 60 years
- All sexes
- Child, Adult
Study population: Patients aged 5-20 with genetically proven CMT1A, patients aged 16-60 with genetically proven CMT1B and CMT2A and male patients aged 16-60 with genetically proven CMTX1
Who may be able to join
- 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.
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- 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.
- 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.
Who cannot join
- 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
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Queen Square Centre for Neuromuscular Diseases
London, WC1n3BG
About this study
This cohort 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. If they show interest in participating, they will be given the relevant Patient Information Sheets, Written Consent forms and/or Assent forms. Half of the participants will be recruited at the UK sites (NHNN and GOSH) and the other half at the US collaborating site. Each participant will be invited to two separate research visits (12 months apart) for which travel expenses (return journey) will be reimbursed. 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
Read the 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.
- Conditions
- Charcot-Marie-Tooth Disease, Type IA, Charcot-Marie-Tooth Disease Type 2A, Charcot-Marie-Tooth Disease, Type IB, Charcot-Marie-Tooth Disease, Type X
- Medical subject headings
- Charcot-Marie-Tooth Disease, Charcot-Marie-Tooth disease, Type 2A, Charcot-Marie-Tooth disease, X-linked, 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Participants with CMT | Participants with CMT1A, CMT1B, CMT2A or CMTX1 | |
| Control participants | Control participants |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI Change in fat accumulation in CMT1A
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.
Measured: 12 months
MRI Change in fat accumulation in CMT1B; CMT2A and CMTX1
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.
Measured: 12 months
Secondary outcomes (5)
MRI changes validation - CMTPedS
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).
Measured: 12 months
MRI changes validation - CMTESv2-R
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
Measured: 12 months
NEFL plasma responsiveness
Defining the responsiveness of plasma NEFL in patients with CMT compared to matched controls over 12 months.
Measured: 12 months
NEFL plasma (biomarker)
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.
Measured: 12 months
Multi-level T2-weighted STIR and plasma NEFL levels (biomarker)
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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2018
- Study start11 Sep 2018
- Primary completion1 Jul 2021 (estimated)
- Study completion1 Oct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Charcot-Marie-Tooth Disease, Type IAStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- University of Iowa
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03550300
- Sponsor's protocol ID
- 18/0244
- Status last verified
- May 2018
- First submitted
- 14 May 2018
- Last updated
- 4 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Muscle MRI in Charcot Mary Tooth Disease: a Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT03550300
- Acronym / sponsor ID
- 18/0244
- Conditions
- Charcot-Marie-Tooth Disease, Type IA, Charcot-Marie-Tooth Disease Type 2A, Charcot-Marie-Tooth Disease, Type IB, Charcot-Marie-Tooth Disease, Type X
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- University of Iowa
- Study start
- 11 Sep 2018 (actual)
- Primary completion
- 1 Jul 2021 (estimated)
- Study completion
- 1 Oct 2021 (estimated)
- First posted
- 8 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This cohort 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. If they show interest in participating, they will be given the relevant Patient Information Sheets, Written Consent forms and/or Assent forms. Half of the participants will be recruited at the UK sites (NHNN and GOSH) and the other half at the US collaborating site. Each participant will be invited to two separate research visits (12 months apart) for which travel expenses (return journey) will be reimbursed. 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
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants with CMT | – | –Participants with CMT1A, CMT1B, CMT2A or CMTX1 |
| Control participants | – | –Control participants |
Who may qualify
- Ages
- 5 to 60 years
- Sex
- All
- Age groups
- Child, Adult
- Study population
- Patients aged 5-20 with genetically proven CMT1A, patients aged 16-60 with genetically proven CMT1B and CMT2A and male patients aged 16-60 with genetically proven CMTX1
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
- Participants with known diagnosis of another neuromuscular disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
5 secondary outcomes
MRI changes validation - CMTPedS
Time frame: 12 months
MRI changes validation - CMTESv2-R
Time frame: 12 months
NEFL plasma responsiveness
Time frame: 12 months
NEFL plasma (biomarker)
Time frame: 12 months
Multi-level T2-weighted STIR and plasma NEFL levels (biomarker)
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Charcot-Marie-Tooth Disease, Type IA and Charcot-Marie-Tooth Disease Type 2A, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Carolynne Doherty (02076794466, c.doherty@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRI Change in fat accumulation in CMT1A (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2018.