PolyneuropathiesPhase 2NCT00050245
Rituximab to Treat Neuropathy With Anti-MAG Antibodies
A Phase 2 study testing Rituximab in people with Polyneuropathies, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Polyneuropathies
- What is being tested?
- Rituximab
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Nov 2002to 17 Oct 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Safety, Tolerability, and Efficacy of Rituximab in Patients With Anti-Glycoconjugate Antibody-Mediated Demyelinating Neuropathy: A Double-Blind Placebo-Controlled Randomized Trial
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.
Read more
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.
Read the 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.
- Conditions
- Polyneuropathies
- Being tested
- Rituximab
- Keywords
- Neuropathy, B Cells, Anti-MAG, Demyelination, MAG, RITUXAN, Monoclonal Antibodies, Retuximab, Demyelinating Neuropathy
- Medical subject headings
- Polyneuropathies, Demyelinating Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in neurological performance using the INCAT scales.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2002 (estimated)
- Study start27 Nov 2002
- Study completion17 Oct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PolyneuropathiesStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00050245
- Sponsor's protocol ID
- 030057
- Other IDs
- 03-N-0057
- Status last verified
- 17 Oct 2007
- First submitted
- 2 Dec 2002
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
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.
PubMed 8619518
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability, and Efficacy of Rituximab in Patients With Anti-Glycoconjugate Antibody-Mediated Demyelinating Neuropathy: A Double-Blind Placebo-Controlled Randomized Trial
- ClinicalTrials.gov ID
- NCT00050245
- Acronym / sponsor ID
- 030057
- Conditions
- Polyneuropathies
- Keywords
- Neuropathy, B Cells, Anti-MAG, Demyelination, MAG, RITUXAN, Monoclonal Antibodies, Retuximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 27 Nov 2002
- Study completion
- 17 Oct 2007
- First posted
- 3 Dec 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab | Drug | – |
Primary outcome
Changes in neurological performance using the INCAT scales.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 8619518Dalakas 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Polyneuropathies, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in neurological performance using the INCAT scales.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00050245, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.