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| Sponsored by: |
National Institute of Neurological Disorders and Stroke (NINDS) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00050245 |
Purpose
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:
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Polyneuropathies |
Drug: Rituximab |
Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment |
| Official Title: | Safety, Tolerability, and Efficacy of Rituximab in Patients With Anti-Glycoconjugate Antibody-Mediated Demyelinating Neuropathy: A Double-Blind Placebo-Controlled Randomized Trial |
| Estimated Enrollment: | 30 |
| Study Start Date: | November 2002 |
| Estimated Study Completion Date: | October 2007 |
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.
Eligibility| Ages Eligible for Study: | 25 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
EXCLUSION CRITERIA:
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.
Contacts and Locations More Information
| Study ID Numbers: | 030057, 03-N-0057 |
| Study First Received: | December 2, 2002 |
| Last Updated: | October 19, 2007 |
| ClinicalTrials.gov Identifier: | NCT00050245 History of Changes |
| Health Authority: | United States: Federal Government |
|
Neuropathy B Cells Anti-MAG Demyelination MAG |
RITUXAN Monoclonal Antibodies Retuximab Neuropathy Demyelinating Neuropathy |
|
Antibodies, Monoclonal Antibodies Immunologic Factors Neuromuscular Diseases Rituximab |
Peripheral Nervous System Diseases Polyneuropathies Antirheumatic Agents Immunoglobulins |
|
Antibodies Immunologic Factors Neuromuscular Diseases Antineoplastic Agents Rituximab Therapeutic Uses |
Peripheral Nervous System Diseases Physiological Effects of Drugs Nervous System Diseases Polyneuropathies Antirheumatic Agents Pharmacologic Actions |
