EVALUATION OF SERUM INFLAMMATORY CYTOKINE CONCENTRATION IN HEREDITARY SENSITIVOMOTOR NEUROPATHIES (CytokinesUS)

EVALUATION OF SERUM INFLAMMATORY CYTOKINE CONCENTRATION

The most common forms of hereditary neuropathy are Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with hypersensitivity to pressure (HNPP) or tomacular neuropathy. A number of patients with one of these pathologies have inflammatory infiltrates in their nerves. Although the pathophysiology has not yet been well understood, the involvement of the immune system has been discussed. Nerve hypertrophy is the main anomaly described in ultrasound in demyelinating hereditary neuropathies and to a lesser extent in axonal forms. Investigators propose to understand if there is a circulating marker of inflammation in patients with CMT or HNPP and find a correlation between the increase in plasma pro-inflammatory cytokines and ultrasound changes.

Study Overview

• Status: Completed
• Conditions: Charcot-Marie-Tooth Disease; Hereditary Neuropathy With Hypersensitivity to Pressure
• Intervention / Treatment: Diagnostic test: blood test for pro-inflammatory cytokines and ultrasound of the median nerves

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Alpes Maritimes
    • Grasse, Alpes Maritimes, France, 06000
      • Grasse CH
    • Nice, Alpes Maritimes, France, 06000
      • Nice CHU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for patients:

• Patient over 18 years of age
• Patient with CMT of HNPP with genetic confirmation, or acquired acute inflammatory disease such as Guillain-Barré syndrome
• Patient able to walk alone or with a walking aid.
• Patient affiliated to a social security scheme,
• Patient who has given his consent in writing after written and oral information

Inclusion Criteria for Healthy Volunteers:

• Patient over 18 years of age
• Patient affiliated to a social security scheme,
• Patient who has given his consent in writing after written and oral information -

Exclusion Criteria:

• Subject protected by law under guardianship or curators, or not able to participate in a clinical study under article L. 1121-16 of the French Public Health Code;
• Subject who has participated in a clinical research study during the last 3 months where he/she was exposed to a pharmaceutical product or medical device;
• Subject who has stayed in a tropical or subtropical country during the last 3 months;
• Pregnant or breastfeeding subject for women of childbearing age;
• Subject who has been physically active for less than 10 hours;
• Subject on a particular diet for medical reasons and prescribed by a doctor or dietitian (e.g., low-calorie or cholesterol-lowering diet);
• Person who regularly consumes large amounts of alcohol, i.e. more than 50 g of pure alcohol per day (for example, more than 4 glasses of wine 150 ml, more than 4 beers 250 ml, or more than 4 glasses of 40 ml containing a strong alcohol);
• Person who has used an illicit recreational drug in the last 3 months;
• Subject who has taken an immunosuppressive or immunomodulatory drug (except for intranasal or topical corticosteroids) in the last 2 weeks, or for more than 14 consecutive days in the last 6 months;
• Subject who has been vaccinated in the last 3 months;
• Subject who received a blood transfusion or immunoglobulins in the last 3 months;
• Person reporting not having fasted for at least 10 hours;
• Person reporting human immunodeficiency virus, hepatitis B virus or hepatitis C virus ;
• Subject who has had an infectious episode in the 3 weeks preceding the visit;
• Test positive for pregnancy urine;
• Subject with severe and/or chronic and/or recurrent disease
• Subject diagnosed with cancer and not in remission for more than 5 years.
• (only for patients) Other associated peripheral nerve pathology already diagnosed (inherited neuropathy or acquired neuropathy from another etiology).
• (only for Health volunteers) Presence of functional or physical signs of involvement of the median nerves, ulnar, external Sciatica Poplitea, internal Sciatica Poplitea, sural

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Identify a circulating marker of inflammation in patients with CMT or HNPP; CMT = Charcot-Marie-Tooth disease HNPP = hereditary neuropathy with hypersensitivity to pressure	Diagnostic test: blood test for pro-inflammatory cytokines and ultrasound of the median nerves; Blood test and ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare serum interleukin IL-1β between different subgroups of patients with genetic neuropathy (demyelinating/axonal/intermediate Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with hypersensitivity to pressure (HNPP)) and a control group.	Serum interleukin IL-1β will be measured using v-plex MSD (Meso Scale Discovery) technology. The IL-1β concentrations will be expressed in ng/ml by calibration with a standard range	at inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the serum concentration of pro-inflammatory cytokines among the different subgroups of patients with genetic neuropathy (demyelinating/axonal/intermediate CMT, HNPP) and with a homogeneous group of control subjects.	A blood sample for measuring inflammatory cytokines (interleukins IL-6, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12 p70, IL-12/IL-23 p40, IL-13, IL-15, IL-16, IL-17A, interferon γ, Tumor necrosis factor α and β, Granulocyte-Macrophage Colony-Stimulating Factor, vascular endothelial growth factor, Chemokines CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26, and CXCL10) using v-plex technology (MesoScale Discovery)	at inclusion
Compare morphological characteristics obtained by high-frequency ultrasound between the different subgroups of subjects	The descriptive analysis of the morphology of the nerves will be carried out using a high-frequency ultrasound (28-33 megahertz, Canon Device) . The cross section area of the nerve will determine . The fascicular organization will be characterized according to 3 types: type 1 (enlarged nerve with hypoechoic nervous fascicles), type 2 (enlarged nerve with the juxtaposition of hypo and hyperechoic fascicles) and type 3 (normal-sized nerve with hypoechoic fascicles poorly differentiated from each other and spiny). Hypervascularity will be evaluated by a doppler signal at the endoneural vessels. The ultrastructural characterization of different types of fascicular organization will also be studied.	within 2 months after inclusion
Study the relationship between ultrasound data and plasma levels of pro-inflammatory cytokines within the different subgroups of subjects	Serum pro-inflammatory cytokine concentration will be measured using v-plex MSD (Meso Scale Discovery) technology. The ultrasound data taken into account will be the cross section area of the nerve, the echogenicity of the nerve and the presence of hypervascularisation	within 2 months after inclusion
Study the link between the plasma level of pro-inflammatory cytokines and electrophysiological data obtained by performing electroneurography (ENG) within the different subgroups of subjects	Serum pro-inflammatory cytokine concentration will be measured using v-plex MSD (Meso Scale Discovery) technology. The electrophysiological data will be obtained at the and pre-defined observation sites of the motor nerves: distal latency (in milliseconds); motor conduction velocity (m/s); conduction block: drop in the amplitude and area of the of compound muscle action potential (amplitude in mV).	within 2 months after inclusion
Study the relationship between ultrasound and electrophysiological data obtained by an electroneurography (ENG) within the different subgroups of subjects	The ultrasound data taken into account will be the cross section area of the nerve, the echogenicity of the nerve and the evaluation of the nerve vascularisation. The electrophysiological data will be obtained at the pre-defined observation site of the motor nerves: distal latency (in milliseconds); motor conduction velocity (m/s);conduction block: drop in the amplitude and area of the compound muscle action potential (amplitude in mV).	within 2 months after inclusion
Study the relationship between serum concentration of pro-inflammatory cytokines among the different subgroups of patients and clinical scores within different subgroups of subjects using functional assessment scale CMT Neuropathy Score 2 (CMTNS2)	Serum pro-inflammatory cytokine concentration will be measured using v-plex MSD (Meso Scale Discovery) technology. The CMT Neuropathy Score 2 (CMTNS2) is a scale used to assess the severity of neuropathy in Charcot-Marie-Tooth disease. The minimum score is 0, indicating no neuropathy, while the maximum score is 36, corresponding to very severe neuropathy. Scores can be divided into four categories: 0 to 4 indicates mild neuropathy, 5 to 14 moderate neuropathy, 15 to 24 severe neuropathy, and 25 to 36 very severe neuropathy. CMTNS2 includes the assessment of sensory symptoms such as paresthesia and pain, motor symptoms such as distal muscle weakness, functional ability based on gait and autonomy, muscle strength, vibration sensitivity, and nerve conduction velocity. This score is used to monitor disease severity	within 2 months after inclusion
Study the relationship between ultrasound data and the iMAX value: Study the relationship between ultrasound data and IMAX value.	The correlation study between structural changes observed in ultrasound and IMAX values will be conducted as indicated in the previous paragraphs.	within 2 months after inclusion

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2022
• Primary Completion (Actual): October 10, 2024
• Study Completion (Actual): October 10, 2024

Study Registration Dates

• First Submitted: January 30, 2025
• First Submitted That Met QC Criteria: January 30, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Hypersensitivity; Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy
• Other Study ID Numbers: 21-AOI-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No