- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04249752
Biomarkers in Polyradiculoneuropathies (BIP)
New Biomarkers in Acute and Chronic Inflammatory Demyelinating Polyradiculoneuropathies
Study Overview
Status
Conditions
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Guillaume Taieb, MD
- Phone Number: 33 467337822
- Email: g-taieb@chu-montpellier.fr
Study Contact Backup
- Name: Jérôme Devaux, PhD
- Email: Jerome.devaux@inserm.fr
Study Locations
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-
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Montpellier, France, 34295
- Recruiting
- UH Montpellier
-
Contact:
- Jérôme Devaux, PhD
- Email: Jerome.devaux@inserm.fr
-
Contact:
- Guillaume Taieb, MD
- Email: g-taieb@chu-montpellier.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
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Group 1 with GBS patients
GBS patients
|
Group 2 with CIDP patients
with CIDP patients
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlation between clinical features and immunoreactivity findings in GBS and CIDP patients
Time Frame: 24 months
|
Correlation between the localization of the staining (i.e.
node of Ranvier, paranodal region, and/or myelin sheath) and the axonal or demyelinating nature of the neuropathy (according to GBS and CIDP criteria).
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Screening and titration of antibodies against new antigenic targets in GBS and CIDP patients.
Time Frame: 5 years
|
The serums of patients will be considered seropositives when optical density value is ≥ 0.1 in ELISA
|
5 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Guillaume Taieb, MD, UH Montpellier
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Immune System Diseases
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Neuromuscular Diseases
- Peripheral Nervous System Diseases
- Polyneuropathies
- Guillain-Barre Syndrome
- Polyradiculoneuropathy
- Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Other Study ID Numbers
- RECHMPL20_0024
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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