Clinical Trials Logo

Clinical Trial Summary

Demyelinating diseases represent a broad spectrum of disorders and are induced by excessive inflammation most often triggered by an autoimmune mechanism. Some of these pathologies are chronic and affect the central nervous system such as multiple sclerosis (MS), others are monophasic and target the peripheral nervous system such as Guillain Barré syndrome (GBS). In neuroinflammatory pathologies, the excessive response of the pro-inflammatory Th1 and Th17 lymphocyte lines and the insufficient response of regulatory T lymphocytes (Treg) cause excessive inflammation which is deleterious to the nervous tissue. The regulation of these signaling pathways involves key proteins such as kinases. Modulation of these kinases which could allow the development of new pharmacological targets for neuroinflammation. Recent work (unpublished data) has shown an association between the expression of ERK5 and PMK2 kinases, and the clinical severity of experimental allergic encephalomyelitis, a mouse model that mimics multiple sclerosis. In order to search for new biomarkers and improve our knowledge of the actors of the initial inflammatory phase of neuroinflammatory pathologies, we propose to study the differences in expression of ERK5 and PKM2 kinases in the blood and cerebral spinal fluid (CSF) of patients followed for relapsing-remitting MS and GBS by both RT-qPCR and protein quantification. We also want to study other biological parameters which include characterization of the pro / anti-inflammatory balance by cytokine assay and lymphocyte phenotyping, metabolome study, and mild form neurofilament (NfL) assay.


Clinical Trial Description

The study of the expression of ERK5 and PKM2 kinases in patients followed for RR MS or GBS, at the beginning of the pathology, will be evaluate. The usual diagnostic workup for MS and GBS will be performed in order to classify patients into 4 groups : • Group 1 : control group. Patients that do not fulfill the criteria for MS or GBS and in whom no differential diagnosis was made. Subgroups 1a and 1b will be formed by respective pairing with groups 2 and 3. - Group 2 : patients with RR MS confirmed by Macdonald criteria (2017) - Group 3 : patients with GBS confirmed by the association of the usual clinical and electrophysiological signs. - Group 4 : patients in whom a differential diagnosis has been identified to explain the symptoms. These patients will be excluded from the analysis. An additional blood sample (25 mL) and cerebrospinal fluid (CSF) sample (2mL) will be taken from all patients in order to study the laboratory parameters of this study. Peripheral blood mononuclear cells (PBMCs) and neutrophils will be isolated from the blood using a Percoll gradient. Group 4 samples will not be analyzed. The analysis will focus on the comparison of laboratory parameters between group 2 and 3, between group 1a and 2, and between 1b and 3. 1. / Expression of ERK5 and PKM2 kinases The investigators wish to analyze the expression of ERK5 and PKM2 by RT-qPCR to investigate the transcriptome on RNA level and by Western Blot and ELISA to investigate the phosphorylated and total forms of the two kinases. RT-qPCR require RNA extraction, reverse transcription into cDNA and then amplification of the genes encoding ERK5 and PKM2 using specific primers designed beforehand. The results will be compared with those obtained with primers of the HPRT gene. 2. / Study of the balance between pro and anti-inflammatory action The investigators wish to characterize the balance of pro and anti-inflammatory activity by studying lymphocyte phenotyping and determining the level of cytokines. Lymphocyte phenotyping will be performed by flow cytometry from PBMCs. The populations studied will include the Th1, Th2, Th9, Th17, Th22, Treg and TFH populations. The panel of mainly inflammatory cytokines will be studied in plasma and in CSF by ELISA. The panel includes the following cytokines: IL17, TNF, IL6, Il 1β, IL 10, IL33, IL12, IL 23 3. / Metabolome analysis The databases on human metabolomes include more than 40,000 metabolites and allow the establishment of metabolic profiles in different pathological contexts by supervised and unsupervised statistical analysis techniques. Metabolome analyzes will be performed from plasma and CSF. These analyzes will be carried out by liquid chromatography coupled with mass spectrometry (LC-MS) by the Metabohub network (MetaboHUB-Clermont for plasma analyzes and MetaboHUB-Saclay for CSF analyzes). 4. / Measure of the neurofilament light chain (NfL) There is growing interest in neurofilament's measure in the blood and in particular in the CSF. High levels of neurofilaments are evidence of neuronal loss, regardless of the initial mechanism. Neurofilament light chain (NfL) seems to be the most relevant form to measure axonal loss. In MS, increased NfL was observed during the first two months of acute relapse. Conversely, there are few data on the kinetics of NfL's levels in peripheral demyelinating diseases. The investigators intend to study NfL levels in blood and CSF to determine if there is an increase in NfL levels in patients followed for GBS and to compare NfL levels of these patients (group 3) with patients followed for MS (group 2). ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04674163
Study type Interventional
Source Centre Hospitalier Régional d'Orléans
Contact
Status Withdrawn
Phase N/A
Start date January 2023
Completion date January 2023

See also
  Status Clinical Trial Phase
Completed NCT03995979 - Inflammation and Protein Restriction N/A
Completed NCT03255187 - Effect of Dietary Supplemental Fish Oil in Alleviating Health Hazards Associated With Air Pollution N/A
Completed NCT04507867 - Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III N/A
Completed NCT03577223 - Egg Effects on the Immunomodulatory Properties of HDL N/A
Completed NCT04383561 - Relationship Between LRG and Periodontal Disease N/A
Active, not recruiting NCT03622632 - Pilot Study to Measure Uric Acid in Traumatized Patients: Determinants and Prognostic Association
Completed NCT06216015 - Exercise Training and Kidney Transplantation N/A
Completed NCT04856748 - Nomogram to Diagnose Prostatic Inflammation (PIN) in Men With Lower Urinary Tract Symptoms
Completed NCT05529693 - Efficacy of a Probiotic Strain on Level of Markers of Inflammation in an Elderly Population N/A
Recruiting NCT05415397 - Treating Immuno-metabolic Depression With Anti-inflammatory Drugs Phase 3
Recruiting NCT05670301 - Flemish Joint Effort for Biomarker pRofiling in Inflammatory Systemic Diseases N/A
Recruiting NCT04543877 - WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study Early Phase 1
Recruiting NCT05775731 - Markers of Inflammation and of the Pro-thrombotic State in Hospital Shift and Day Workers
Completed NCT03859934 - Metabolic Effects of Melatonin Treatment Phase 1
Completed NCT03429920 - Effect of Fermented Soy Based Product on Cardiometabolic Risk Factors N/A
Completed NCT06065241 - Quantifiably Determine if the Botanical Formulation, LLP-01, Has a Significant Clinical Effect on Proteomic Inflammatory Biomarkers and Epigenetic Changes in Healthy, Older Individuals. N/A
Completed NCT05864352 - The Role of Dietary Titanium Dioxide on the Human Gut Microbiome and Health
Completed NCT03318731 - Efficacy and Safety of Fenugreek Extract on Markers of Muscle Damage and Inflammation in Untrained Males N/A
Not yet recruiting NCT06134076 - Comparing Effects of Fermented and Unfermented Pulses and Gut Microbiota N/A
Not yet recruiting NCT06422494 - The Role of the Adrenergic System in Hypoglycaemia Induced Inflammatory Response in People With Type 1 Diabetes and People Without Type 1 Diabetes-RAID-II N/A