Rituximab to Treat Neuropathy With Anti-MAG Antibodies
Condition: Polyneuropathies
MeSH terms: Polyneuropathies
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will test the safety and effectiveness of the drug Rituximab in treating a nerve
      disease called MGUS (also known as neuropathy with anti-MAG antibodies). Patients with MGUS
      have an abnormal protein called monoclonal IgM immunoglobulin that attacks the myelin sheath
      (protective coating) of nerves, causing them to not function properly. The disease affects
      the nerves in the legs or arms, and patients have numbness, tingling, muscle weakness, and
      unsteady gait. There are no adequate treatments. Immunosuppressive drugs or human
      immunoglobulin infusions can produce mild and transient improvement, but the benefits of
      these therapies are not significant.

      The abnormal immunoglobulin protein in MGUS is produced by white cells called B lymphocytes.
      Rituximab is approved to treat B cell lymphomas. Also, the drug showed promise in a recent
      study of patients with demyelinating neuropathy associated with production of antibodies from
      B lymphocytes directed against certain nerve proteins. Although the number of patients
      treated with Rituximab was small, the drug was well tolerated and caused significant
      improvement in several of the patients.

      Patients 25 years of age and older with MGUS may be eligible for this 2-year study.
      Candidates will be screened with a medical history, physical and neurological examinations,
      and blood tests.

      Participants will be randomly assigned to receive intravenous (through a vein) infusions of
      either Rituximab or placebo (a solution that looks like Rituximab but has no active
      ingredient) once a week for 4 consecutive weeks. In addition, they will undergo the following
      tests and procedures:

        -  Monthly follow-up visits following Rituximab treatment for repeat physical and
           neurological examinations, blood tests, muscle strength measurements, and review of
           signs and symptoms.

        -  Two sessions of lymphapheresis, one at the beginning of the study and one a year
           later-to collect lymphocytes. For this procedure, whole blood is drawn through a needle
           in an arm vein, much like donating a unit of blood. The blood then flows through a
           catheter (plastic tube) into a cell separating machine, where the white blood cells are
           extracted and removed. The red cells and plasma are then returned to the body through a
           needle in the other arm. The procedure takes about 60 to 90 minutes.

        -  Electrophysiologic studies (electromyography and nerve conduction testing) are done once
           at the beginning of the study and again one year later. For electromyography, a small
           needle is inserted into a few muscles and the patient is asked to relax or to contract
           the muscles. The electrical activity of the muscle cells is recorded and analyzed by a
           computer. For nerve conduction testing, nerves are stimulated through small wire
           electrodes attached to the skin and the response is recorded and analyzed.

      If this study indicates that Rituximab is beneficial against MGUS, patients who were assigned
      to receive placebo during the trial will be offered treatment with Rituximab (four weekly
      infusions) at the end of the study.
    

Detailed description: 
      This study will examine the safety, tolerability, and efficacy of the humanized monoclonal
      antibody Rituximab to induce a clinical and serological remission in patients with
      IgM-anti-glycoconjugate antibody-mediated demyelinating neuropathy. Rituximab is a monoclonal
      antibody specific for the common B cell antigen CD20. Its administration depletes pre-B and
      mature B lymphocytes without altering neutrophils or hematopoietic stem cells. In humans with
      indolent B cell lymphomas, Rituximab can be safely administered, is well tolerated, promotes
      selective B cell depletion and lowers the serum IgM levels. Preliminary experience in some
      patients with demyelinating polyneuropathy and IgM-anti-glycolipid antibodies has shown that
      Rituximab was beneficial in improving the patient's symptoms and reducing the anti IgM
      antibody levels. In the present study we will examine in a placebo randomized trial the
      efficacy of Rituximab in patients with polyneuropathy related to IgM-anti-glycolipid
      antibodies. Twenty-six patients will be randomized to receive placebo or Rituximab given at
      four weekly intravenous infusions of 375 mg/M(2). The primary outcome will be based on
      changes in the monthly measurements of the neuropathy scores. The fine specificities of the
      IgM antibodies to various glycoconjugates or differences in the affinity binding to various
      antigens in neural membranes will be explored before and after treatment. It is anticipated
      that the study will: a) provide a new, immune-based and target-oriented therapy for patients
      with this neuropathy and b) examine the pathogenic role of these antibodies in the cause of
      the disease.
    

Intervention name(s): Rituximab
Intervention type(s): Drug
Intervention MeSH terms: Rituximab
Primary purpose: Treatment
Keywords: Neuropathy; B Cells; Anti-MAG; Demyelination; MAG; RITUXAN; Monoclonal Antibodies; Retuximab; Demyelinating Neuropathy