Polyneuropathies Clinical Trial
Official title:
Safety, Tolerability, and Efficacy of Rituximab in Patients With Anti-Glycoconjugate Antibody-Mediated Demyelinating Neuropathy: A Double-Blind Placebo-Controlled Randomized Trial
Verified date | October 17, 2007 |
Source | National Institutes of Health Clinical Center (CC) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 30 |
Est. completion date | October 17, 2007 |
Est. primary completion date | |
Accepts healthy volunteers | No |
Gender | All |
Age group | 25 Years to 80 Years |
Eligibility |
- INCLUSION CRITERIA: 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. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Neurological Disorders and Stroke (NINDS) |
United States,
Dalakas MC, Quarles RH. Autoimmune ataxic neuropathies (sensory ganglionopathies): are glycolipids the responsible autoantigens? Ann Neurol. 1996 Apr;39(4):419-22. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Changes in neurological performance using the INCAT scales. |
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