RIMAG Study: Trial of Rituximab Versus Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy

Study Overview
=================
Brief Summary
-----------------
Polyneuropathy associated with anti-MAG monoclonal IgM gammopathy is responsive of mainly a sensory deficit in predominantly males ,aged 40-70 years. Significantly high serum anti-MAG antibodies are linked with demyelinating features of the peripheral nerves.Rituximab, an anti-CD 20 monoclonal antibody is a new drug which reduces B-lymphocytes. This study will test the safety and efficacy of rituximab in the treatment of patients with anti-MAG polyneuropathy.

Detailed Description
-----------------
Acting of a polyneuropathy for which there is not any treatment of reference today (see supra), a test of double-knowledge versus placebo is justified. Acting of a chronic polyneuropathy, the clinical evaluation must be led over one one year period. Acting of a sensitive polyneuropathy and the awaited benefit being the IMPROVEMENT OF the CLINICAL SIGNS, the principal criterion is a sensitive score in addition validated in chronic sensitive polyneuropathies immunodeficiency syndrome. The patients answering the criteria of inclusion and none inclusion (see V-2) will be randomized in 2 groups: the first group will receive a perfusion IV of rituximab to the amount of 375 mg/m2 of body surface, once per week, during 4 weeks (see VII-3); the second group will receive 4 perfusions IV of placebo according to same methods'. The evaluation (see VI-1) will be carried out at the time of the randomization, then repeated in 3 months, 6 months, 9 months and 1 year.

Official Title
-----------------
Double-blind Randomized Trial of Rituximab Versus Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy

Conditions
-----------------
Polyneuropathy

Intervention / Treatment
-----------------
* Drug: Rituximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: IgM monoclonal gammopathy Anti-MAG antibody titers > 1.1000 BTU (ELISA) Worsening polyneuropathy with INCAT score > 4 Informed consent Exclusion Criteria: Severe comorbidity Other concurrent causes of polyneuropathy Concurrent immunosuppressive therapies (wash-out > 3 months) Previous treatment with rituximab Lymphoproliferative disease indicating other immunosuppressive treatment Unability to follow-up Previous documented side-effects with components involved in the tested drug White cell count < 1500/mm3 or platelet count < 75.000/mm3 Patient under law

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 82 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Rituximab | Drug: Rituximab<br>* Rituximab<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| INCAT sensory score at 1 year | INCAT sensory score at 1 year | during de study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional scales, MRC score | Functional scales, MRC score | during the study | 
| Quality of life (SF 36) | Quality of life (SF 36) | during the study | 
| Serum lymphocytes count, IgM level, anti-MAG antibody titers | Serum lymphocytes count, IgM level, anti-MAG antibody titers | during the study | 
| Electrophysiological parameters | Electrophysiological parameters | during the study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anti-MAG monoclonal gammopathy, Polyneuropathy, Rituximab