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CompletedNCT03268161GENOMAGUpdated Feb 27, 2018

Prevalence of Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies

An observational study in Neuropathy Demyelinating, sponsored by Rennes University Hospital. Completed at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-02-27.

Sponsored by Rennes University Hospital · Observational

Study type
Observational
Model
Cohort
Time perspective
Retrospective
Enrollment
26
Ages
18 Years and older
Sex
All
01

Study summary

Anti-MAG (Myelin Associated Glycoprotein) neuropathy is related to clonal B lymphocyte proliferation producing an monoclonal immunoglobulin (IgM) with anti-MAG activity. IgM may be a reflection of malignant lymphoproliferative syndrome (Waldenström disease) or, more often, monoclonal gammopathy of unknown significance.

The anti-MAG antibody has a direct toxicity on the myelin sheath of the peripheral nervous system responsible for a length-dependent demyelinating polyneuropathy. Clinically, this results in a sensitive, ataxic predominant polyneuropathy in the lower limbs, sometimes associated with a tremor of attitude and action tremor of the upper limbs.

Clonal B cells at the origin of IgM production may have acquired mutations affecting MYD88 (MYD88 L265P mutation) and CXCR4 (Whim-like CXCR4 mutation). The prevalence of the MYD88 L265P mutation is estimated to be 50% in monoclonal gammopathies of undetermined significance and more than 80% in Waldenström disease. CXCR4 Whim-like mutations are found in 40% of patients with Waldenström's disease.

No studies have reported the prevalence of these mutations in patients with anti-MAG neuropathies.

Read the detailed description

This is a retrospective observational study in patients with anti-MAG neuropathy. Mutational analysis will be performed for patients with a medullary or blood sample stored in a bio-bank during lymphocyte phenotyping. This phenotyping was carried out most often in search of a malignant haemopathy associated with the monoclonal peak. No new samples were taken from the patient (blood or spinal cord).

Immunoglobulin gene rearrangement of the clonal B cells are also assessed.

02

Conditions studied

  • Neuropathy Demyelinating

Keywords

  • anti-MAG neuropathy
  • Waldenström disease
  • Mutational analysis
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Patients with anti-MAG neuropathy followed in the Internal Medicine Ward of the Rennes University Hospital

Inclusion criteria

  • Patients with anti-MAG neuropathy
  • Blood and/or bone marrow samples available in bio-bank
  • Given informed consent

Exclusion criteria

Exclusion criterion

  • Participation refusal
04

Study design

Observational model
Cohort
Time perspective
Retrospective
Enrollment
26 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • Patients with anti-MAG neuropathy

    Mutational analysis of clonal B cells

    Diagnostic Test: Mutational analysis of clonal B cells

Interventions

  • Diagnostic testMutational analysis of clonal B cells

    Mutational analysis based on medullary or blood samples stored in a bio-bank during routine lymphocyte phenotyping. Mutations affecting MYD88 (MYD88 L265P mutation), CXCR4 (Whim-like CXCR4 mutation) loci are sought.

05

What researchers measure

Primary outcomes

  1. Prevalence of MYD88 L265P mutations in anti-MAG neuropathies

    Mutational status of MYD88 L265P is assessed using high-throughput sequencing (HTS) and allele specific polymerase chain reaction (AS-PCR)

    Time frame: At inclusion : after the patient's given consent

  2. Prevalence of CXCR4 Whim-like mutations in anti-MAG neuropathies

    Mutational status of CXCR4 is assessed using HTS and AS-PCR

    Time frame: At inclusion : after the patient's given consent

Secondary outcomes

  1. Immunoglobulin gene rearrangement

    Immunoglobulin gene rearrangements are determined with a multiplex PCR

    Time frame: At inclusion : after the patient's given consent

06

Study locations

1 site
  • Rennes University Hospital
    Rennes, 35000, France
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03268161
Lead sponsor
Rennes University Hospital
Responsible party
Sponsor
First posted
Aug 31, 2017
Start date
Oct 21, 2015
Primary completion
Nov 10, 2017
Completion
Nov 10, 2017
Last update
Feb 27, 2018

Study contacts

Olivier DECAUX, MD, PhD
study director · CHU Rennes

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Feb 2018. You cannot join it, but the record below documents what was studied.

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