Charcot-Marie-ToothCMT-NFSNCT07461896
Studying Nerve Function and Structure in Charcot-Marie-Tooth Disease, Anti-MAG Neuropathy and CIDP
An observational study of Charcot-Marie-Tooth and CMT1A, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 1 site in Italy.
Trial summary
The project aims to perform both conventional nerve-conduction studies and axonal-excitability assessments using the TRONDF protocol in patients with selected forms of Charcot-Marie-Tooth disease, with comparison to individuals affected by dysimmune, acquired neuropathies, specifically chronic inflammatory… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Charcot-Marie-Tooth, CMT1A, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
- How many people
- 39 participants
- Where
- 1 siteItaly
- Study dates
- 3 Mar 2025to May 2026
- Phase
- Observational
- 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
Study population: * A minimum of 30 patients with a genetically confirmed diagnosis of CMT * At least 15 patients diagnosed with either Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or anti-myelin associated glycoprotein (MAG) polyneuropathy as a disease control group.
Who may be able to join
- The subject is ≥ 18 years old.
- AND:
- A genetically confirmed diagnosis of one of the several CMT subtypes (i.e., CMT1A, CMT1B, CMTX1, CMT2I/J, CMT4B, CMT4D and CMT4J) OR
- A clinical diagnosis of either Chronic Inflammatory Demyelinating Polyneuropathy or anti-MAG polyneuropathy
Who cannot join
- Known neuropathy from another cause (e.g., diabetes, chronic renal insufficiency, medications, alcohol), including previous carpal tunnel syndrome surgery.
- History of exposure to chemotherapeutic agents (e.g., bortezomib, vincristine, cisplatin, taxol, vedotin/auromycin-conjugated antibodies), or other medications (e.g., disulfuram, thalidomide, voriconizole, chronic colchicine use) that can cause neuropathy, active alcohol abuse.
- History of cancer, other than skin cancer, within 5 years prior to enrollment.
- Pregnancy or nursing.
- Known systemic disease that predisposes to neuropathy.
- Other central nervous system diseases.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133
Davide Pareyson, MD, + 39 02.2394, davide.pareyson@istituto-besta.it
About this study
Official title: Axonal Excitability and Ultrasound Patterns in Charcot-Marie-Tooth Disease and Other Demyelinating Disorders
The project aims to perform both conventional nerve-conduction studies and axonal-excitability assessments using the TRONDF protocol in patients with selected forms of Charcot-Marie-Tooth disease, with comparison to individuals affected by dysimmune, acquired neuropathies, specifically chronic inflammatory demyelinating polyneuropathy (CIDP) and anti-MAG-neuropathy. The study further includes the analysis of nerve fibers obtained from skin biopsy in patients with CMT, as well as ultrasound evaluation of nerves (from the wrist to the axilla) and of intrinsic hand muscles. Axonal-excitability techniques involve the delivery of two electrical stimuli to the nerve under investigation; both stimuli vary in intensity, whereas only the first, known as the conditioning stimulus, varies in duration. Changes in response amplitude are then measured as these stimulation parameters are systematically adjusted. Some preliminary studies have already suggested the effectiveness of this method in distinguishing CMT1A from certain forms of acquired demyelinating disease, including acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and CIDP. Despite the promising results, only a limited number of studies have so far been conducted in humans and mice, and no comprehensive and systematic study has yet been carried out describing the changes in axonal excitability in the various CMT subtypes, either in humans or in mouse models.
Read the detailed description
Charcot-Marie-Tooth neuropathy (CMT) is the most prevalent hereditary neuromuscular disorder, estimated to affect 11.8 to 82.3 individuals per 100,000 in Europe. While genetic assessment is increasingly gaining significance, neurophysiology continues to play a crucial role in classifying CMT into axonal, intermediate or demyelinating forms. Despite its diagnostic importance, standard neurophysiology techniques may prove inadequate to reliably capture disease progression, advocating for the adoption of newer methodologies in the near future. Among these, axonal excitability testing, providing information about the properties of axonal membranes insight into the behaviour of voltage-gated ion channels, pump and exchangers involved in impulse conduction, could have potential additional diagnostic and prognostic value in neuromuscular disorder.
Axonal excitability techniques provide insights into ion channel function, serving as an in vivo surrogate markers of axonal membrane potential in human axons. Recent advancements in this field have standardized procedures, increased execution speed, and minimized patients' discomfort enabling routine clinical application. These advancements include the development of standardized semi-automated recording setups and the publication of international guidelines. It is plausible that progressive ion-channel dysfunction and spontaneous baseline depolarization of nerves maybe associated with disease severity and response to therapy (in patients with acquired polyneuropathies).
Investigators plan to study a series of patients with different types of CMT with this technique and compare results with diseased controls affected by dysimmune neuropathies and corresponding mouse models, by conventional nerve conduction studies, by electrical nerve stimulation to study neuronal excitability as below depicted, and by examining myelinated skin nerves by performing skin biopsy in a subset of patients.
Moreover, literature data demonstrate that nerve ultrasound supports the diagnosis and follow-up of neuromuscular disorders. In the context of neuropathies, nerve ultrasound enables an anatomical and structural evaluation that provides useful data for the differential diagnosis between hereditary and acquired forms. In particular, in Charcot-Marie-Tooth disease, nerve ultrasound allows the identification of pathognomonic patterns that can significantly guide genetic testing (e.g CMT1A).
In severe acquired forms, where the pathological process is so extensive that clear electrophysiological findings are not always present, nerve ultrasound can detect specific alterations that may help guiding the diagnosis. Moreover, nerve ultrasound can identify certain features that may suggest (and correlate with) the severity of the disease.
Muscle ultrasound in neuromuscular disorders is instead a more recent application. The detection of specific patterns of muscle involvement can suggest a possible regional distribution, described in some nosological entities. Furthermore, literature data show that the structural and ultrasound characteristics of the muscle correlate with the degree of strength deficit. Despite the increasing amount of literature in the field, no nerve or muscle ultrasound studies have yet been published on some acquired forms and rare forms of Charcot-Marie-Tooth disease. The collection and analysis of ultrasound data in these cases would allow for a broader understanding of the related pathological processes, potentially identifying patterns that support diagnosis and follow-up.
Collaborators for this project are the following: Inherited Neuropathy Consortium (INC); Prof. Christian Krarup (Dept of Clin. Neurophys., Rigshospitalet, Copenhagen, DK; Dept of Neuroscience, Univ. of Copenhagen, Copenhagen, DK); Prof. Mihai Moldovan (Dept of Neurol., North Zealand Hospital, Hillerød, DK; Dept of Clin. Neurophys., Rigshospitalet, Copenhagen, DK; Dept of Neuroscience, Univ. of Copenhagen, Copenhagen, DK); Prof. Hatice Tankisi (Aarhus University Hospital, Department of Clinical Neurophysiology, Aarhus, Denmark; Aarhus University, Department of Clinical Medicine, Aarhus, Denmark)
- Conditions
- Charcot-Marie-Tooth, CMT1A, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Polyneuropathy Associated With Anti-MAG Antibodies (Anti-MAG Polyneuropathy), Anti-MAG Neuropathy
- Keywords
- Charcot-Marie-Tooth, Neurophysiology, Axonal excitability, Ultrasound (US), CMT1A, CMT1B, CMTX1, CMT2I/J, CMT4B2, CMT4D, CMT4J, CIDP, anti-MAG
- Medical subject headings
- Charcot-Marie-Tooth Disease, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Charcot-Marie-Tooth disease, X-linked, 1, Charcot-Marie-Tooth disease, Type 4B2, Neuropathy, hereditary motor and sensory, LOM type
What is being measured
The primary outcome is the main question the study is designed to answer.
Strength-Duration Time Constant
Strength-duration time constant (SDTC, ms) measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy).
Measured: 2 years
Recovery Cycle of Nerve Excitability Parameters
Recovery cycle of nerve excitability parameters measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy), including superexcitability and late subexcitability (% threshold change)
Measured: 2 years
Threshold Electrotonus
Threshold Electrotonus (TE, % threshold change at specified time intervals) measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy).
Measured: 2 years
Current-Threshold (I/V) Relationship
Current-threshold (I/V) relationship parameters (e.g., slope of threshold change versus polarizing current) measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy).
Measured: 2 years
Secondary outcomes (4)
Peripheral nerve cross-sectional area by ultrasound
Cross-sectional area (CSA, mm²) of the median and ulnar nerves measured by ultrasound from the wrist to the axilla in participants with Charcot-Marie-Tooth disease, CIDP, and anti-MAG neuropathy.
Measured: 2 years
Muscle thickness by ultrasound
Muscle thickness (mm) of the abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles measured by ultrasound in participants with Charcot-Marie-Tooth disease, CIDP, and anti-MAG neuropathy.
Measured: 2 years
Muscle echogenicity by ultrasound (Heckmatt scale)
Muscle echogenicity graded using the Heckmatt scale (grades 1-4) in the abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles.
Heckmatt scale grading:
Grade 1: normal Grade 2: increased muscle echogenicity with preserved architecture and normal bone reflection Grade 3: increased echogenicity with partial loss of architecture and reduced bone reflection Grade 4: markedly increased echogenicity with complete loss of architecture and absent bone reflection
Measured: 2 years
Correlation of ultrasound parameters with clinical and electrophysiological measures
Correlation between ultrasound parameters (nerve CSA, muscle thickness, and Heckmatt grade) and clinical severity measured by CMTNS/CMTES and axonal excitability parameters.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start3 Mar 2025
- Primary completionMay 2026 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Charcot-Marie-ToothStudies 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Davide Pareyson, MD, Principal investigator, Fondazione IRCCS Istituto Neurologico Carlo Besta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07461896
- Sponsor's protocol ID
- CMT-NFS
- Acronym
- CMT-NFS
- Status last verified
- Jan 2026
- First submitted
- 29 Jan 2026
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shahrizaila N, Noto Y, Simon NG, Huynh W, Shibuya K, Matamala JM, Dharmadasa T, Devenney E, Kennerson ML, Nicholson GA, Kiernan MC. Quantitative muscle ultrasound as a biomarker in Charcot-Marie-Tooth neuropathy. Clin Neurophysiol. 2017 Jan;128(1):227-232. doi: 10.1016/j.clinph.2016.11.010. Epub 2016 Nov 21.
PubMed 27940147Padua L, Granata G, Sabatelli M, Inghilleri M, Lucchetta M, Luigetti M, Coraci D, Martinoli C, Briani C. Heterogeneity of root and nerve ultrasound pattern in CIDP patients. Clin Neurophysiol. 2014 Jan;125(1):160-5. doi: 10.1016/j.clinph.2013.07.023. Epub 2013 Oct 5.
PubMed 24099922Noto Y, Shiga K, Tsuji Y, Mizuta I, Higuchi Y, Hashiguchi A, Takashima H, Nakagawa M, Mizuno T. Nerve ultrasound depicts peripheral nerve enlargement in patients with genetically distinct Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry. 2015 Apr;86(4):378-84. doi: 10.1136/jnnp-2014-308211. Epub 2014 Aug 4.
PubMed 25091364Schreiber S, Oldag A, Kornblum C, Kollewe K, Kropf S, Schoenfeld A, Feistner H, Jakubiczka S, Kunz WS, Scherlach C, Tempelmann C, Mawrin C, Dengler R, Schreiber F, Goertler M, Vielhaber S. Sonography of the median nerve in CMT1A, CMT2A, CMTX, and HNPP. Muscle Nerve. 2013 Mar;47(3):385-95. doi: 10.1002/mus.23681. Epub 2013 Feb 4.
PubMed 23381770Manganelli F, Nolano M, Pisciotta C, Provitera V, Fabrizi GM, Cavallaro T, Stancanelli A, Caporaso G, Shy ME, Santoro L. Charcot-Marie-Tooth disease: New insights from skin biopsy. Neurology. 2015 Oct 6;85(14):1202-8. doi: 10.1212/WNL.0000000000001993. Epub 2015 Sep 11.
PubMed 26362287Nobbio L, Visigalli D, Radice D, Fiorina E, Solari A, Lauria G, Reilly MM, Santoro L, Schenone A, Pareyson D; CMT-TRIAAL Group. PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker. Brain. 2014 Jun;137(Pt 6):1614-20. doi: 10.1093/brain/awu071. Epub 2014 May 8.
PubMed 24812204Burke D, Kiernan MC, Bostock H. Excitability of human axons. Clin Neurophysiol. 2001 Sep;112(9):1575-85. doi: 10.1016/s1388-2457(01)00595-8.
PubMed 11514239Kiernan MC, Burke D, Andersen KV, Bostock H. Multiple measures of axonal excitability: a new approach in clinical testing. Muscle Nerve. 2000 Mar;23(3):399-409. doi: 10.1002/(sici)1097-4598(200003)23:33.0.co;2-g.
PubMed 10679717Bostock H, Cikurel K, Burke D. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve. 1998 Feb;21(2):137-58. doi: 10.1002/(sici)1097-4598(199802)21:23.0.co;2-c.
PubMed 9466589Moldovan M, Alvarez S, Pinchenko V, Klein D, Nielsen FC, Wood JN, Martini R, Krarup C. Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is detrimental to motor axons. Brain. 2011 Feb;134(Pt 2):585-601. doi: 10.1093/brain/awq336. Epub 2010 Dec 17.
PubMed 21169333Rosberg MR, Alvarez S, Klein D, Nielsen FC, Martini R, Levinson SR, Krarup C, Moldovan M. Progression of motor axon dysfunction and ectopic Nav1.8 expression in a mouse model of Charcot-Marie-Tooth disease 1B. Neurobiol Dis. 2016 Sep;93:201-14. doi: 10.1016/j.nbd.2016.05.014. Epub 2016 May 20.
PubMed 27215377Nasu S, Misawa S, Nakaseko C, Shibuya K, Isose S, Sekiguchi Y, Mitsuma S, Ohmori S, Iwai Y, Beppu M, Shimizu N, Ohwada C, Takeda Y, Fujimaki Y, Kuwabara S. Bortezomib-induced neuropathy: axonal membrane depolarization precedes development of neuropathy. Clin Neurophysiol. 2014 Feb;125(2):381-7. doi: 10.1016/j.clinph.2013.07.014. Epub 2013 Aug 21.
PubMed 23973385Lin CS, Krishnan AV, Park SB, Kiernan MC. Modulatory effects on axonal function after intravenous immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy. Arch Neurol. 2011 Jul;68(7):862-9. doi: 10.1001/archneurol.2011.137.
PubMed 21747028Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC. Oxaliplatin-induced neurotoxicity: changes in axonal excitability precede development of neuropathy. Brain. 2009 Oct;132(Pt 10):2712-23. doi: 10.1093/brain/awp219. Epub 2009 Sep 10.
PubMed 19745023Sung JY, Kuwabara S, Kaji R, Ogawara K, Mori M, Kanai K, Nodera H, Hattori T, Bostock H. Threshold electrotonus in chronic inflammatory demyelinating polyneuropathy: correlation with clinical profiles. Muscle Nerve. 2004 Jan;29(1):28-37. doi: 10.1002/mus.10516.
PubMed 14694495
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Axonal Excitability and Ultrasound Patterns in Charcot-Marie-Tooth Disease and Other Demyelinating Disorders
- ClinicalTrials.gov ID
- NCT07461896
- Acronym / sponsor ID
- CMT-NFS / CMT-NFS
- Conditions
- Charcot-Marie-Tooth, CMT1A, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Polyneuropathy Associated With Anti-MAG Antibodies (Anti-MAG Polyneuropathy), Anti-MAG Neuropathy
- Keywords
- Charcot-Marie-Tooth, Neurophysiology, Axonal excitability, Ultrasound (US), CMT1A, CMT1B, CMTX1, CMT2I/J
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
- Study start
- 3 Mar 2025 (actual)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 10 Mar 2026 (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 project aims to perform both conventional nerve-conduction studies and axonal-excitability assessments using the TRONDF protocol in patients with selected forms of Charcot-Marie-Tooth disease, with comparison to individuals affected by dysimmune, acquired neuropathies, specifically chronic inflammatory demyelinating polyneuropathy (CIDP) and anti-MAG-neuropathy. The study further includes the analysis of nerve fibers obtained from skin biopsy in patients with CMT, as well as ultrasound evaluation of nerves (from the wrist to the axilla) and of intrinsic hand muscles. Axonal-excitability techniques involve the delivery of two electrical stimuli to the nerve under investigation; both stimuli vary in intensity, whereas only the first, known as the conditioning stimulus, varies in duration. Changes in response amplitude are then measured as these stimulation parameters are systematically adjusted. Some preliminary studies have already suggested the effectiveness of this method in distinguishing CMT1A from certain forms of acquired demyelinating disease, including acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and CIDP. Despite the promising results, only a limited number of studies have so far been conducted in humans and mice, and no comprehensive and systematic study has yet been carried out describing the changes in axonal excitability in the various CMT subtypes, either in humans or in mouse models.
Detailed description
Charcot-Marie-Tooth neuropathy (CMT) is the most prevalent hereditary neuromuscular disorder, estimated to affect 11.8 to 82.3 individuals per 100,000 in Europe. While genetic assessment is increasingly gaining significance, neurophysiology continues to play a crucial role in classifying CMT into axonal, intermediate or demyelinating forms. Despite its diagnostic importance, standard neurophysiology techniques may prove inadequate to reliably capture disease progression, advocating for the adoption of newer methodologies in the near future. Among these, axonal excitability testing, providing information about the properties of axonal membranes insight into the behaviour of voltage-gated ion channels, pump and exchangers involved in impulse conduction, could have potential additional diagnostic and prognostic value in neuromuscular disorder.
Axonal excitability techniques provide insights into ion channel function, serving as an in vivo surrogate markers of axonal membrane potential in human axons. Recent advancements in this field have standardized procedures, increased execution speed, and minimized patients' discomfort enabling routine clinical application. These advancements include the development of standardized semi-automated recording setups and the publication of international guidelines. It is plausible that progressive ion-channel dysfunction and spontaneous baseline depolarization of nerves maybe associated with disease severity and response to therapy (in patients with acquired polyneuropathies).
Investigators plan to study a series of patients with different types of CMT with this technique and compare results with diseased controls affected by dysimmune neuropathies and corresponding mouse models, by conventional nerve conduction studies, by electrical nerve stimulation to study neuronal excitability as below depicted, and by examining myelinated skin nerves by performing skin biopsy in a subset of patients.
Moreover, literature data demonstrate that nerve ultrasound supports the diagnosis and follow-up of neuromuscular disorders. In the context of neuropathies, nerve ultrasound enables an anatomical and structural evaluation that provides useful data for the differential diagnosis between hereditary and acquired forms. In particular, in Charcot-Marie-Tooth disease, nerve ultrasound allows the identification of pathognomonic patterns that can significantly guide genetic testing (e.g CMT1A).
In severe acquired forms, where the pathological process is so extensive that clear electrophysiological findings are not always present, nerve ultrasound can detect specific alterations that may help guiding the diagnosis. Moreover, nerve ultrasound can identify certain features that may suggest (and correlate with) the severity of the disease.
Muscle ultrasound in neuromuscular disorders is instead a more recent application. The detection of specific patterns of muscle involvement can suggest a possible regional distribution, described in some nosological entities. Furthermore, literature data show that the structural and ultrasound characteristics of the muscle correlate with the degree of strength deficit. Despite the increasing amount of literature in the field, no nerve or muscle ultrasound studies have yet been published on some acquired forms and rare forms of Charcot-Marie-Tooth disease. The collection and analysis of ultrasound data in these cases would allow for a broader understanding of the related pathological processes, potentially identifying patterns that support diagnosis and follow-up.
Collaborators for this project are the following: Inherited Neuropathy Consortium (INC); Prof. Christian Krarup (Dept of Clin. Neurophys., Rigshospitalet, Copenhagen, DK; Dept of Neuroscience, Univ. of Copenhagen, Copenhagen, DK); Prof. Mihai Moldovan (Dept of Neurol., North Zealand Hospital, Hillerød, DK; Dept of Clin. Neurophys., Rigshospitalet, Copenhagen, DK; Dept of Neuroscience, Univ. of Copenhagen, Copenhagen, DK); Prof. Hatice Tankisi (Aarhus University Hospital, Department of Clinical Neurophysiology, Aarhus, Denmark; Aarhus University, Department of Clinical Medicine, Aarhus, Denmark)
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * A minimum of 30 patients with a genetically confirmed diagnosis of CMT * At least 15 patients diagnosed with either Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or anti-myelin associated glycoprotein (MAG) polyneuropathy as a disease control group.
Key inclusion criteria (4 listed)
- The subject is ≥ 18 years old.
- A genetically confirmed diagnosis of one of the several CMT subtypes (i.e., CMT1A, CMT1B, CMTX1, CMT2I/J, CMT4B, CMT4D and CMT4J) OR
- A clinical diagnosis of either Chronic Inflammatory Demyelinating Polyneuropathy or anti-MAG polyneuropathy
Key exclusion criteria (6 listed)
- Known neuropathy from another cause (e.g., diabetes, chronic renal insufficiency, medications, alcohol), including previous carpal tunnel syndrome surgery.
- History of exposure to chemotherapeutic agents (e.g., bortezomib, vincristine, cisplatin, taxol, vedotin/auromycin-conjugated antibodies), or other medications (e.g., disulfuram, thalidomide, voriconizole, chronic colchicine use) that can cause neuropathy, active alcohol abuse.
- History of cancer, other than skin cancer, within 5 years prior to enrollment.
- Pregnancy or nursing.
- Known systemic disease that predisposes to neuropathy.
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
Strength-Duration Time Constant
Time frame: 2 years
Strength-duration time constant (SDTC, ms) measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy).
Recovery Cycle of Nerve Excitability Parameters
Time frame: 2 years
Recovery cycle of nerve excitability parameters measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy), including superexcitability and late subexcitability (% threshold change)
Threshold Electrotonus
Time frame: 2 years
Threshold Electrotonus (TE, % threshold change at specified time intervals) measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy).
Current-Threshold (I/V) Relationship
Time frame: 2 years
Current-threshold (I/V) relationship parameters (e.g., slope of threshold change versus polarizing current) measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy).
4 secondary outcomes
Peripheral nerve cross-sectional area by ultrasound
Time frame: 2 years
Muscle thickness by ultrasound
Time frame: 2 years
Muscle echogenicity by ultrasound (Heckmatt scale)
Time frame: 2 years
Correlation of ultrasound parameters with clinical and electrophysiological measures
Time frame: 2 years
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 10 Mar 2026.
- Background: PubMed 27940147Shahrizaila N, Noto Y, Simon NG, Huynh W, Shibuya K, Matamala JM, Dharmadasa T, Devenney E, Kennerson ML, Nicholson GA, Kiernan MC. Quantitative muscle ultrasound as a biomarker in Charcot-Marie-Tooth neuropathy. Clin Neurophysiol. 2017 Jan;128(1):227-232. doi: 10.1016/j.clinph.2016.11.010. Epub 2016 Nov 21.
- Background: PubMed 24099922Padua L, Granata G, Sabatelli M, Inghilleri M, Lucchetta M, Luigetti M, Coraci D, Martinoli C, Briani C. Heterogeneity of root and nerve ultrasound pattern in CIDP patients. Clin Neurophysiol. 2014 Jan;125(1):160-5. doi: 10.1016/j.clinph.2013.07.023. Epub 2013 Oct 5.
- Background: PubMed 25091364Noto Y, Shiga K, Tsuji Y, Mizuta I, Higuchi Y, Hashiguchi A, Takashima H, Nakagawa M, Mizuno T. Nerve ultrasound depicts peripheral nerve enlargement in patients with genetically distinct Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry. 2015 Apr;86(4):378-84. doi: 10.1136/jnnp-2014-308211. Epub 2014 Aug 4.
- Background: PubMed 23381770Schreiber S, Oldag A, Kornblum C, Kollewe K, Kropf S, Schoenfeld A, Feistner H, Jakubiczka S, Kunz WS, Scherlach C, Tempelmann C, Mawrin C, Dengler R, Schreiber F, Goertler M, Vielhaber S. Sonography of the median nerve in CMT1A, CMT2A, CMTX, and HNPP. Muscle Nerve. 2013 Mar;47(3):385-95. doi: 10.1002/mus.23681. Epub 2013 Feb 4.
- Background: PubMed 26362287Manganelli F, Nolano M, Pisciotta C, Provitera V, Fabrizi GM, Cavallaro T, Stancanelli A, Caporaso G, Shy ME, Santoro L. Charcot-Marie-Tooth disease: New insights from skin biopsy. Neurology. 2015 Oct 6;85(14):1202-8. doi: 10.1212/WNL.0000000000001993. Epub 2015 Sep 11.
- Background: PubMed 24812204Nobbio L, Visigalli D, Radice D, Fiorina E, Solari A, Lauria G, Reilly MM, Santoro L, Schenone A, Pareyson D; CMT-TRIAAL Group. PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker. Brain. 2014 Jun;137(Pt 6):1614-20. doi: 10.1093/brain/awu071. Epub 2014 May 8.
- Background: PubMed 11514239Burke D, Kiernan MC, Bostock H. Excitability of human axons. Clin Neurophysiol. 2001 Sep;112(9):1575-85. doi: 10.1016/s1388-2457(01)00595-8.
- Background: PubMed 10679717Kiernan MC, Burke D, Andersen KV, Bostock H. Multiple measures of axonal excitability: a new approach in clinical testing. Muscle Nerve. 2000 Mar;23(3):399-409. doi: 10.1002/(sici)1097-4598(200003)23:33.0.co;2-g.
- Background: PubMed 9466589Bostock H, Cikurel K, Burke D. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve. 1998 Feb;21(2):137-58. doi: 10.1002/(sici)1097-4598(199802)21:23.0.co;2-c.
- Background: PubMed 21169333Moldovan M, Alvarez S, Pinchenko V, Klein D, Nielsen FC, Wood JN, Martini R, Krarup C. Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is detrimental to motor axons. Brain. 2011 Feb;134(Pt 2):585-601. doi: 10.1093/brain/awq336. Epub 2010 Dec 17.
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- 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.
Davide Pareyson, MD principal investigator
Fondazione IRCCS Istituto Neurologico Carlo Besta
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 and CMT1A, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 1 site in Italy.
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 4 inclusion and 6 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 10 Mar 2026. 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 Italy. 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 Davide Pareyson, MD (+ 39 02.2394, davide.pareyson@istituto-besta.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Strength-Duration Time Constant (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07461896, which also lists 21 linked publications.
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 10 Mar 2026.