Rituximab to Treat Neuropathy With Anti-MAG Antibodies

NCT00050245 | Completed Phase 2

• 2 other identifiers: 03005703-N-0057
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Polyneuropathies

Keywords

Neuropathy; B Cells; Anti-MAG; Demyelination; MAG; RITUXAN; Monoclonal Antibodies; Retuximab; Demyelinating Neuropathy

Outcome Measures

Primary Outcomes (1)

• Changes in neurological performance using the INCAT scales.

Interventions

Rituximab DRUG

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Research subjects will have documented disability of IgM anti-glycoconjugate antibody-mediated demyelinating neuropathy.
• Neuropathy associated with IgM monoclonal immunoglobulins reactivate to MAG or other glycoconjugates.
• Willingness and legal ability to give and sign informed study consent.
• Willingness to travel to NIH for scheduled protocol studies and treatment.
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
• Adequate bone marrow, renal, and liver function: ANC greater than 1000/mm3, BUN/Cr with normal range for age, AST or ALT less than 2 x of upper limit of normal.

You may not qualify if:

• Immunosuppressive drug therapy at the time of or 6 months prior to enrollment. Specifically, candidates may not be taking prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, anti-lymphocyte agents, cyclophosphamide, methotrexate, or other agents whose therapeutic effect is immunosuppressive or could provoke neuropathy as undesirable secondary effect.
• Any medical or social condition that precludes follow-up visits.
• Any active malignancy or any history of a hematogenous malignancy or lymphoma. Patients with melanoma will be excluded. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are treated prior to enrollment.
• Coagulopathy or requirement for anticoagulation therapy that would contraindicate protocol.
• Platelet count less than 100,000/mm(3).
• Hemoglobin less than 7.0 mg/dl.
• Any known immunodeficiency syndrome included HIV infection.
• Any history of cardiac insufficiency, major vascular disease, or symptomatic coronary artery disease. Patients with cardiomyopathy grade III or IV by the New York Heart Classification will be excluded from this study.
• Systemic edema or pulmonary edema.
• Chronic hypotension (SBP less than 100 mm Hg).
• Any condition that would likely increase the risk of protocol participation or confound the interpretation of the data including active infections.
• Pregnancy. Serum pregnancy test will be performed and must be negative in all women of childbearing potential enrolled in the study.
• History of active psychiatric disorder that may interfere with participation in the study.
• Patients below the age of 25 because this neuropathy does not occur in such age groups.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Dalakas MC, Quarles RH. Autoimmune ataxic neuropathies (sensory ganglionopathies): are glycolipids the responsible autoantigens? Ann Neurol. 1996 Apr;39(4):419-22. doi: 10.1002/ana.410390402. No abstract available.

  PMID: 8619518 BACKGROUND

MeSH Terms

Conditions

Polyneuropathies; Demyelinating Diseases

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: December 2, 2002
• First Posted: December 3, 2002
• Study Start: November 27, 2002
• Study Completion: October 17, 2007
• Last Updated: July 2, 2017

Record last verified: 2007-10-17

Locations

US (1)