Ignite Creation Date:
2024-05-05 @ 11:37 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00091897
Status:
COMPLETED
Last Update Posted:
2011-08-31
First Post:
2004-09-18
Brief Title:
Rituximab to Treat Stiff Person Syndrome
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Efficacy of Rituximab in Patients With Stiff Person Syndrome With Anti-GAD Antibodies A Randomized Placebo-Controlled Trial
Status:
COMPLETED
Status Verified Date:
2011-08
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 whether rituximab RITUXAN Trademark can relieve symptoms of stiff person syndrome SPS a progressive disease that causes stiffness of the muscles and muscle spasms induced by unexpected noises touches or stressful events People with SPS may have certain proteins in their blood called anti-GAD antibodies that may cause some of the symptoms of the disease Rituximab a drug approved to treat lymphomas targets certain white blood cells that produce antibodies This study will see if rituximab can also be effective in patients with SPS who have high anti-GAD antibodies
Patients between 25 and 80 years of age with SPS may be eligible for this study Candidates are screened with a medical history physical examination and blood tests Participants undergo the following tests and procedures
Rituximab or placebo treatment Patients are randomly assigned to receive two infusions by vein of either rituximab or placebo a look-alike solution with no active ingredient 2 weeks apart The infusions last from 3 to 4 hours but may take as long as 16 hours if the rate must be slowed for any reason Patients are followed monthly for up to 6 months and then every 2 months for up to 1 year after treatment
Medical history and interview physical and neurological examinations Patients are questioned about their vaccination history medical surgical and psychiatric history exposure to environmental toxins or viruses and family and social history including habits and employment
Blood drawing Blood samples are collected before the two infusions and at all follow-up visits
Apheresis For this procedure which is used to collect white blood cells blood is collected through a needle in an arm vein similar to donating blood The blood flows from the vein through a catheter plastic tube into a machine that separates it into its components by centrifugation spinning The white cells are removed and the rest of the blood red cells plasma and platelets is returned to the body through a second needle in the other arm The procedure takes about 60 to 90 minutes
Lumbar puncture spinal tap Lumbar puncture is done to sample a small amount of cerebrospinal fluid CSF the fluid that bathes the brain and spinal cord for analysis For this procedure the patient is given a local anesthetic and a needle is inserted into the space between the bones in the lower back where the CSF circulates below the spinal cord A small amount of fluid is withdrawn through the needle
Patients between 25 and 80 years of age with SPS may be eligible for this study Candidates are screened with a medical history physical examination and blood tests Participants undergo the following tests and procedures
Rituximab or placebo treatment Patients are randomly assigned to receive two infusions by vein of either rituximab or placebo a look-alike solution with no active ingredient 2 weeks apart The infusions last from 3 to 4 hours but may take as long as 16 hours if the rate must be slowed for any reason Patients are followed monthly for up to 6 months and then every 2 months for up to 1 year after treatment
Medical history and interview physical and neurological examinations Patients are questioned about their vaccination history medical surgical and psychiatric history exposure to environmental toxins or viruses and family and social history including habits and employment
Blood drawing Blood samples are collected before the two infusions and at all follow-up visits
Apheresis For this procedure which is used to collect white blood cells blood is collected through a needle in an arm vein similar to donating blood The blood flows from the vein through a catheter plastic tube into a machine that separates it into its components by centrifugation spinning The white cells are removed and the rest of the blood red cells plasma and platelets is returned to the body through a second needle in the other arm The procedure takes about 60 to 90 minutes
Lumbar puncture spinal tap Lumbar puncture is done to sample a small amount of cerebrospinal fluid CSF the fluid that bathes the brain and spinal cord for analysis For this procedure the patient is given a local anesthetic and a needle is inserted into the space between the bones in the lower back where the CSF circulates below the spinal cord A small amount of fluid is withdrawn through the needle
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 Stiff Person Syndrome SPS associated with high anti-GAD antibodies 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 IgG and IgM levels Preliminary experience in some non-malignant antibody-mediated disorders has shown that Rituximab was beneficial in improving the patients symptoms and reducing antibody level
SPS is an antibody-mediated autoimmune disease affecting GABA-ergic transmission resulting in incapacitating stiffness and spasms The anti-GAD antibodies are also produced intrathecally and it is believed to be responsible for the reduction of GABA level in serum and CSF Although removal or modulation of serum antibodies by plasmapheresis or IVIg results in clinical improvement a number of patients do not respond or their response is modest and short-lived and remain with significant disability The need for more effective therapy prompted us to conduct the present study to examine in a randomized trial if Rituximab is effective in patients with GAD-antibody-positive SPS
Twenty-four patients will be randomized in a double blind fashion to receive placebo or Rituximab given at a fixed dose of 1 GM on Day 1and 1 GM on day 15 plus or minus 2 days The primary outcome will be based on measurements of stiffness using the Distribution of Stiffness Index Secondary outcomes will be measured by the Heightened-Sensitivity Scales The serum and CSF anti-GAD antibody titers including intrathecal GAD-specific IgG synthesis will be monitored before and after treatment Clearance of GAD-reactive T cells will be also examined in the serum and CSF using T cell clones established from PBL and CSF It is anticipated that the study will a provide a new immune-based and target-oriented therapy for patients with Stiff Person Syndrome and b examine the pathogenetic role of anti-GAD antibodies in the cause of the disease
SPS is an antibody-mediated autoimmune disease affecting GABA-ergic transmission resulting in incapacitating stiffness and spasms The anti-GAD antibodies are also produced intrathecally and it is believed to be responsible for the reduction of GABA level in serum and CSF Although removal or modulation of serum antibodies by plasmapheresis or IVIg results in clinical improvement a number of patients do not respond or their response is modest and short-lived and remain with significant disability The need for more effective therapy prompted us to conduct the present study to examine in a randomized trial if Rituximab is effective in patients with GAD-antibody-positive SPS
Twenty-four patients will be randomized in a double blind fashion to receive placebo or Rituximab given at a fixed dose of 1 GM on Day 1and 1 GM on day 15 plus or minus 2 days The primary outcome will be based on measurements of stiffness using the Distribution of Stiffness Index Secondary outcomes will be measured by the Heightened-Sensitivity Scales The serum and CSF anti-GAD antibody titers including intrathecal GAD-specific IgG synthesis will be monitored before and after treatment Clearance of GAD-reactive T cells will be also examined in the serum and CSF using T cell clones established from PBL and CSF It is anticipated that the study will a provide a new immune-based and target-oriented therapy for patients with Stiff Person Syndrome and b examine the pathogenetic role of anti-GAD 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 |
|---|---|---|---|
| IND-BB 11844 04-N-0287 | None | None | None |