Ignite Creation Date:
2024-05-05 @ 11:28 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00050245
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2002-12-02
Brief Title:
Rituximab to Treat Neuropathy With Anti-MAG Antibodies
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Safety Tolerability and Efficacy of Rituximab in Patients With Anti-Glycoconjugate Antibody-Mediated Demyelinating Neuropathy A Double-Blind Placebo-Controlled Randomized Trial
Status:
COMPLETED
Status Verified Date:
2007-10-17
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 patients 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 mgM2 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-N-0057 | None | None | None |