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Biomarkers in Polyradiculoneuropathies

NCT ID: NCT04249752

Last Updated: 2020-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-01

Study Completion Date

2025-01-30

Brief Summary

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The nodes of Ranvier contain ion channels that enable the rapid propagation of the nerve impulse. Cell adhesion molecules and glycolipids play an important role in the formation of the nodes of Ranvier. Antibodies against glycolipids are detected in half of patients with Guillain-Barré syndrome, an acute inflammatory neuropathy affecting peripheral nerve. The investigators found that antibodies target cell adhesion molecules at nodes of Ranvier in 10% of patients with chronic inflammatory demyelinating neuropathy (CIDP), another disabling neuromuscular disease affecting peripheral nerves. In the majority of patients with GBS or CIDP, the mechanisms responsible for the neuromuscular disorders are unknown. Our goals are to identify novel targets of antibodies in patients, this in order to find novel bio-markers and to better understand the physiopathology of inflammatory neuropathies. This work will help patient diagnosis and treatment orientation.

Detailed Description

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Background: Inflammatory demyelinating polyradiculoneuropathies are rare disabling autoimmune diseases affecting the peripheral nervous system. These neuropathies can be acute, when signs and symptoms raise in less than 1 month (Guillain-Barré syndrome, GBS), or chronic, when deteriorations continue over more than 2 months from onset (CIDP). About half of GBS patients present with IgG1 or IgG3 anti-gangliosides antibodies. Gangliosides are glycolipidic structures mainly localized at the node and paranode areas. In CIDP patients, IgG4 auto-antibodies directed against nodal (Nfasc-186) or paranodal (Nfasc-155, CNTN1, Caspr-1) proteins are found in 5 to 10 %. In most GBS and CIDP patients, the antigenic target are unknown and clinical biomarkers are critically lacking to help diagnosis and treatment orientation. The aim of the present study is to identify new biomarkers in AIDP and CIDP patients.

Methods : The investigators conduct a national retrospective and prospective study to identify new antigenic targets in GBS and CIDP patients. Since 2015, the Institute for Neurosciences of Montpellier and the University Hospitals of Montpellier collect clinical, immulogical, electrophysiological, and histological data of GBS and CIDP patients. Each patient whose serum has already been collected gave written informed consent. GBS and CIDP are diagnosed according to the current criteria. Anti-gangliosides antibodies (by immunodot-blot) and anti-Nfasc155, -CNTN1, -Nfasc186, and -Caspr-1 antibodies (by ELISA and cell-binding assay) are assessed in GBS and CIDP patients, respectively. Among CIDP patients with monoclonal gammapathy, those presenting with anti-MAG antibodies, increasing VEGF, AL amyloidosis, and neurolymphomatosis are excluded. Patients' serum are also tested by immunohistochemical staining on wild-type and GalNacT -/- mouse sciatic nerve fibres.

Clinical and electrophysiological phenotypes are compared between patients with positive and negative immunostaining. Localization of the staining (i.e. node of Ranvier, paranodal region, and/or myelin sheath) as the subclass and isotype of the autoantibody are specified.

The search for a new antigenic target is performed in GBS and CIDP patients which are i) seronegatives for antiganglioside and anti-Nfasc155, -CNTN1, -Nfasc186, and -Caspr-1 antibodies, and presenting with ii) a postive immunostaining on wild-type and GalNacT-/- mouse sciatic nerve fibres. Then, serums of these selected patients are incubated with neuronal and glial cells in culture (spinal dorsal ganglia, motoneurons, Schwann cells, oligodendrocytes and neocortical neurons). In the case of positivity against cell culture, an immunoprecipitation is performed and the antigen/antibody complex is separated on SDS-PAGE 4-12% gel and electrophoretic bands are analyzed by mass spectrometry.

The aim of this study is to identify new antigenic targets in seronegative GBS and CIDP patients displaying immunoreactivity. The knowledge of these new targets may improve our diagnostic tools and could help to develop targeted therapies.

Conditions

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Guillain-Barre Syndrome CIDP

Keywords

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chronic inflammatory demyelinating polyradiculoneuropathy immunostaining autoantibodies

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Group 1 with GBS patients

GBS patients

No interventions assigned to this group

Group 2 with CIDP patients

with CIDP patients

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* GBS or CIDP patients over 18 years old
* Signed informed consent
* With a positive immunostaining on wild-type and GalNacT-/- mouse sciatic nerve fibres.
* Subjects must be covered by public health insurance

Exclusion Criteria

\- seropositive for anti-ganglioside, anti-MAG, and/or anti-Nfasc155, -CNTN1, -Nfasc186, and -Caspr-1 antibodies
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CHU de la Timone, Marseille, France

UNKNOWN

Sponsor Role collaborator

CHU Carémeau, Nîmes, France

UNKNOWN

Sponsor Role collaborator

University Hospital, Bordeaux

OTHER

Sponsor Role collaborator

Centre hospitalier de Perpignan

OTHER

Sponsor Role collaborator

CH de Narbonne, France

UNKNOWN

Sponsor Role collaborator

CH de Béziers France

UNKNOWN

Sponsor Role collaborator

University Hospital, Montpellier

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Guillaume Taieb, MD

Role: STUDY_DIRECTOR

UH MONTPELLIER

Locations

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UH Montpellier

Montpellier, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Guillaume Taieb, MD

Role: CONTACT

Phone: 467337822

Email: [email protected]

Jérôme Devaux, PhD

Role: CONTACT

Email: [email protected]

Facility Contacts

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Guillaume Taieb, MD

Role: primary

Jérôme Devaux, PhD

Role: backup

Other Identifiers

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RECHMPL20_0024

Identifier Type: -

Identifier Source: org_study_id