Muscle MRI in Charcot Mary Tooth Disease: a Prospective Cohort Study

NCT03550300 | Unknown

• 1 other identifier: 18/0244
• Study Type: observational
• Target: 130
• Locations: 1 country
• Sites: 1

Brief 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. 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

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  12 months

Secondary Outcomes (5)

• MRI changes validation - CMTPedS

  12 months

• MRI changes validation - CMTESv2-R

  12 months

• NEFL plasma responsiveness

  12 months

• NEFL plasma (biomarker)

  12 months

• Multi-level T2-weighted STIR and plasma NEFL levels (biomarker)

  12 months

Study Arms (2)

Participants with CMT

Participants with CMT1A, CMT1B, CMT2A or CMTX1

Control participants

Control participants

Eligibility Criteria

• Age: 5 Years - 60 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• University of Iowa: collaborator

Study Sites (1)

Queen Square Centre for Neuromuscular Diseases

London, WC1n3BG, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples for plasma NEFL levels will be optional at both research visits.

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease; Charcot-Marie-Tooth disease, Type 2A; Charcot-Marie-Tooth disease, X-linked, 1

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Central Study Contacts

Carolynne Doherty

CONTACT

02076794466; c.doherty@ucl.ac.uk

Mariola Skorupinska

CONTACT

02031087544; mariola.skorupinska@nhs.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: June 8, 2018
• Study Start: September 11, 2018
• Primary Completion: July 1, 2021
• Study Completion: October 1, 2021
• Last Updated: October 4, 2018

Record last verified: 2018-05

Locations

GB (1)