Charcot-Marie-Tooth Neuropathy Type 1AIMAGINERVNCT06845644
Longitudinal Quantitative Neuromuscular MRI in Neuropathic Patients
A study testing Quantitative neuromuscular MRI and Neuromuscular ultrasound in people with Charcot-Marie-Tooth Neuropathy Type 1A and Hereditary Transthyretin Amyloid Neuropathy, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
The pathophysiological process common to neuropathies is fatty replacement of muscle tissue, more commonly known as intramuscular fat fraction (F.F). MRI is an imaging technique that enables us to distinguish between muscle and fat tissue, and thus to objectify in vivo structural changes within nerves and muscles in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Charcot-Marie-Tooth Neuropathy Type 1A, Hereditary Transthyretin Amyloid Neuropathy, Acquired Demyelinating Neuropathy
- What is being tested?
- Quantitative neuromuscular MRI and Neuromuscular ultrasound
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteFrance
- Study dates
- 23 May 2025to May 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female between 18 and 80 years of age,
- Patients who have freely given their consent to participate in this study,
- Patient with genetically confirmed hereditary CMT neuropathy
- or patient with an acquired demyelinating neuropathy such as typical PIDC or anti-MAG of typical form
- or a patient with a genetically confirmed pathogenic mutation in the transthyretin (TTRn) gene,
- Patients who are beneficiaries or entitled beneficiaries of a social security scheme.
Who cannot join
- Patients with co-morbidity or a history of other peripheral neuropathy,
- Patients with alcohol or psychoactive substance abuse,
- Patients with contraindications to MRI exploration: claustrophobia, pacemakers, Holter systems, IUDs, metal surgical clips, metal prostheses or implants (or other metal foreign bodies),
- Patient unable to perform the MRI due to severe handicap,
- Patient in a period of exclusion from another research protocol at the time of signing the consent/non-opposition form,
- Subjects covered by articles L1121-5 to 1121-8 of the French Public Health Code (minors, adults under guardianship or trusteeship, patients deprived of their liberty, pregnant or breast-feeding women),
- Persons who cannot read and understand the French language well enough to be able to give their consent to participate in research.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Assistance - Publique Hôpitaux de Marseille
Marseille, 13005
Dr FORTANIER, MD, 04 91 38 65 79 ext. +33, etienne.fortanier@ap-hm.fr
Etienne Dr FORTANIER, MD
About this study
Official title: Longitudinal Quantitative Neuromuscular MRI Evaluation in Patients With Acquired and Hereditary Neuropathy
The pathophysiological process common to neuropathies is fatty replacement of muscle tissue, more commonly known as intramuscular fat fraction (F.F). MRI is an imaging technique that enables us to distinguish between muscle and fat tissue, and thus to objectify in vivo structural changes within nerves and muscles in neuropathic patients. In addition to visualizing these changes, quantitative neuromuscular MRI (qMRI) can be used to quantify a number of biomarkers associated with these pathophysiological processes. Over the past few years, this procedure has become a relevant tool in a number of neuromuscular pathologies, such as acquired and hereditary neuropathies. Thanks to its non-ionizing nature and its ability to explore tissues in three dimensions, MRI is the technique of choice for evaluating these diseases, complementing the clinical and electrophysiological scores available.
In a context where numerous therapic strategies are being evaluated for the treatment of peripheral nervous system diseases, the clinical and electrophysiological scores currently available are proving inadequate for the detection of early change or a positive therapeutic effect. On the basis of a limited number of studies, quantitative MRI could provide much more sensitive therapeutic monitoring data over short periods of time which is crucial for future therapeutic trials.
Read more
The most interesting MRI biomarker to date would therefore be the FF, which represents the percentage of fatty infiltration of muscles following pathological nerve damage. Other MRI biomarkers, such as quantified magnetization transfer ratio (MTR), proton density (PD), water transverse relaxation time (wT2) and three-dimensional volume, enable us to study the degenerative and inflammatory phenomena at work in these neuropathies from different angles, detailing the nerve and muscle damage in patients compared with healthy controls or presymptomatic patients. In patients with Charcot-Marie-Tooth (CMT) neuropathy in particular, qMRI is the only tool to detect significant longitudinal variation over a one-year period, revealing an average increase in FF in the lower limbs of +1.5% over 12 months. Confirmation of these results and their extension to other neuropathies such as hereditary amyloid neuropathies (ATTR-PN) or acquired demyelinating neuropathies (ADN) is therefore justified, but requires the implementation of standardized longitudinal studies including these different pathologies.
As strong correlations between these MRI biomarkers and the main clinical scores have been demonstrated in several cross-sectional studies, the clinical value of this non-invasive tool is beyond doubt.
The main limitation to the clinical deployment of this technology remains the time required for the manual segmentation step to delineate the areas of interest. The ongoing development of new image analysis techniques, as well as the contribution of artificial intelligence and deep learning to the imaging data extraction process, are well on the way to solving this problem, but require continuous updating of practices to identify the most interesting MRI biomarkers, facilitate their extraction and thus measure their clinical application with a view to future therapeutic trials.
- Conditions
- Charcot-Marie-Tooth Neuropathy Type 1A, Hereditary Transthyretin Amyloid Neuropathy, Acquired Demyelinating Neuropathy
- Being tested
- Quantitative neuromuscular MRI, Neuromuscular ultrasound
- Keywords
- Neuromuscular MRI, Neuropathy, Intramuscular fat fraction
- Medical subject headings
- Charcot-Marie-Tooth Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quantitative neuromuscular MRIOther
Quantitative neuromuscular MRI is used to quantify a number of biomarkers associated with these pathophysiological processes
Neuromuscular ultrasoundOther
Neuromuscular ultrasound is used to quantified nerve diameter variation
| Study group | Role | What they receive |
|---|---|---|
| Charcot-Marie-Tooth neuropathy (CMT) | Other | Not described Receives: Other: Quantitative neuromuscular MRI |
| Hereditary transthyretin amyloid neuropathy (ATTR-PN) | Other | Not described |
| Acquired demyelinating neuropathy (ADN). | Other | Not described Receives: Other: Quantitative neuromuscular MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annual intramuscular fat fraction progression
Comparison of FF measurement in lower limb muscle using qMRI between inclusion and one year after
Measured: Between inclusion and one year after
Secondary outcomes (7)
Annual percentage change in magnetization transfer ratio (MTR)
Comparison of magnetization transfer ratio in lower limb muscle using qMRI between inclusion and one year after
Measured: Between inclusion and one year after
Annual percentage change in proton density (PD)
Comparison of proton density in lower limb muscle using qMRI between inclusion and one year after
Measured: Between inclusion and one year after
Annual percentage change in transverse relaxation time (T2)
Comparison of transverse relaxation time in lower limb muscle using qMRI between inclusion and one year after
Measured: Between inclusion and one year after
Annual percentage change in 3D volume
Comparison of lower limb muscle 3D volume using qMRI between inclusion and one year after
Measured: Between inclusion and one year after
Correlations between MRI parameters and patients' clinical and electrophysiological parameters
Clinical parameters are: ONLS score, MRC testing and 10-meter walk test (for all patients), CMTNSv2 and CMTES-R scores (for CMT patients), PND, NIS and CADT scores (for ATTR-PN patients), QoL-MND, RODS scale and EVA (for ADN patients). Electrological parameters are obtained by MUNIX technique.
Measured: Between inclusion and one year after
Annual variation of nerve diameter in ATTR-PN patients
Comparison of nerve diameter using neuromuscular ultrasound between inclusion and one year after.
Measured: Between inclusion and one year after
Correlation betxeen ultrasound-quantified nerve diameter variation and clinical and electrophysiological parameters in ATTR-PN patients
Clinical parameters are: ONLS score, MRC testing and 10-meter walk test (for all patients), CMTNSv2 and CMTES-R scores (for CMT patients), PND, NIS and CADT scores (for ATTR-PN patients), QoL-MND, RODS scale and EVA (for ADN patients). Electrological parameters are obtained by MUNIX technique.
Measured: Between inclusion and one year after
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2025
- Study start23 May 2025
- Primary completion23 May 2026 (estimated)
- Study completionMay 2028 (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 Neuropathy Type 1AStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- François CREMIEUX, Study director, Assistance Publique - Hôpitaux de Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06845644
- Sponsor's protocol ID
- RCAPHM24_0268
- Other IDs
- ID-RCB
- Acronym
- IMAGINERV
- Status last verified
- May 2025
- First submitted
- 20 Feb 2025
- Last updated
- 31 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Quantitative Neuromuscular MRI Evaluation in Patients With Acquired and Hereditary Neuropathy
- ClinicalTrials.gov ID
- NCT06845644
- Acronym / sponsor ID
- IMAGINERV / RCAPHM24_0268
- Conditions
- Charcot-Marie-Tooth Neuropathy Type 1A, Hereditary Transthyretin Amyloid Neuropathy, Acquired Demyelinating Neuropathy
- Keywords
- Neuromuscular MRI, Neuropathy, Intramuscular fat fraction
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 23 May 2025 (actual)
- Primary completion
- 23 May 2026 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 25 Feb 2025 (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.
The pathophysiological process common to neuropathies is fatty replacement of muscle tissue, more commonly known as intramuscular fat fraction (F.F). MRI is an imaging technique that enables us to distinguish between muscle and fat tissue, and thus to objectify in vivo structural changes within nerves and muscles in neuropathic patients. In addition to visualizing these changes, quantitative neuromuscular MRI (qMRI) can be used to quantify a number of biomarkers associated with these pathophysiological processes. Over the past few years, this procedure has become a relevant tool in a number of neuromuscular pathologies, such as acquired and hereditary neuropathies. Thanks to its non-ionizing nature and its ability to explore tissues in three dimensions, MRI is the technique of choice for evaluating these diseases, complementing the clinical and electrophysiological scores available.
In a context where numerous therapic strategies are being evaluated for the treatment of peripheral nervous system diseases, the clinical and electrophysiological scores currently available are proving inadequate for the detection of early change or a positive therapeutic effect. On the basis of a limited number of studies, quantitative MRI could provide much more sensitive therapeutic monitoring data over short periods of time which is crucial for future therapeutic trials.
The most interesting MRI biomarker to date would therefore be the FF, which represents the percentage of fatty infiltration of muscles following pathological nerve damage. Other MRI biomarkers, such as quantified magnetization transfer ratio (MTR), proton density (PD), water transverse relaxation time (wT2) and three-dimensional volume, enable us to study the degenerative and inflammatory phenomena at work in these neuropathies from different angles, detailing the nerve and muscle damage in patients compared with healthy controls or presymptomatic patients. In patients with Charcot-Marie-Tooth (CMT) neuropathy in particular, qMRI is the only tool to detect significant longitudinal variation over a one-year period, revealing an average increase in FF in the lower limbs of +1.5% over 12 months. Confirmation of these results and their extension to other neuropathies such as hereditary amyloid neuropathies (ATTR-PN) or acquired demyelinating neuropathies (ADN) is therefore justified, but requires the implementation of standardized longitudinal studies including these different pathologies.
As strong correlations between these MRI biomarkers and the main clinical scores have been demonstrated in several cross-sectional studies, the clinical value of this non-invasive tool is beyond doubt.
The main limitation to the clinical deployment of this technology remains the time required for the manual segmentation step to delineate the areas of interest. The ongoing development of new image analysis techniques, as well as the contribution of artificial intelligence and deep learning to the imaging data extraction process, are well on the way to solving this problem, but require continuous updating of practices to identify the most interesting MRI biomarkers, facilitate their extraction and thus measure their clinical application with a view to future therapeutic trials.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Charcot-Marie-Tooth neuropathy (CMT) | Other | Other: Quantitative neuromuscular MRI |
| Hereditary transthyretin amyloid neuropathy (ATTR-PN) | Other | – |
| Acquired demyelinating neuropathy (ADN). | Other | Other: Quantitative neuromuscular MRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female between 18 and 80 years of age,
- Patients who have freely given their consent to participate in this study,
- Patient with genetically confirmed hereditary CMT neuropathy
- or patient with an acquired demyelinating neuropathy such as typical PIDC or anti-MAG of typical form
- or a patient with a genetically confirmed pathogenic mutation in the transthyretin (TTRn) gene,
Key exclusion criteria (7 listed)
- Patients with co-morbidity or a history of other peripheral neuropathy,
- Patients with alcohol or psychoactive substance abuse,
- Patients with contraindications to MRI exploration: claustrophobia, pacemakers, Holter systems, IUDs, metal surgical clips, metal prostheses or implants (or other metal foreign bodies),
- Patient unable to perform the MRI due to severe handicap,
- Patient in a period of exclusion from another research protocol at the time of signing the consent/non-opposition form,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Quantitative neuromuscular MRIQuantitative neuromuscular MRI is used to quantify a number of biomarkers associated with these pathophysiological processes | Other | Acquired demyelinating neuropathy (ADN)., Charcot-Marie-Tooth neuropathy (CMT) |
| Neuromuscular ultrasoundNeuromuscular ultrasound is used to quantified nerve diameter variation | Other | – |
Primary outcome
Annual intramuscular fat fraction progression
Time frame: Between inclusion and one year after
Comparison of FF measurement in lower limb muscle using qMRI between inclusion and one year after
7 secondary outcomes
Annual percentage change in magnetization transfer ratio (MTR)
Time frame: Between inclusion and one year after
Annual percentage change in proton density (PD)
Time frame: Between inclusion and one year after
Annual percentage change in transverse relaxation time (T2)
Time frame: Between inclusion and one year after
Annual percentage change in 3D volume
Time frame: Between inclusion and one year after
Correlations between MRI parameters and patients' clinical and electrophysiological parameters
Time frame: Between inclusion and one year after
Annual variation of nerve diameter in ATTR-PN patients
Time frame: Between inclusion and one year after
Correlation betxeen ultrasound-quantified nerve diameter variation and clinical and electrophysiological parameters in ATTR-PN patients
Time frame: Between inclusion and one year after
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Individual participant dataSharing planned: No
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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.
François CREMIEUX study director
Assistance Publique - Hôpitaux de Marseille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Quantitative neuromuscular MRI and Neuromuscular ultrasound in people with Charcot-Marie-Tooth Neuropathy Type 1A and Hereditary Transthyretin Amyloid Neuropathy, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
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 6 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: looking for participants now, as of the sponsor's last update on 31 May 2025. 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 France. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Etienne FORTANIER, MD (04 91 38 65 79 ext. +33, etienne.fortanier@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annual intramuscular fat fraction progression (time frame: Between inclusion and one year after). 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 31 May 2025.