Stiff Person SyndromePhase 2NCT00091897
Rituximab to Treat Stiff Person Syndrome
A Phase 2 study testing Rituximab in people with Stiff Person Syndrome, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Stiff Person Syndrome
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2004to May 2009
- 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
- Stiff Person Syndrome with elevated anti-GAD antibody titers.
- Between 25 to 80 years of age.
- Willingness to stop IVIg therapy 6 weeks prior to Rituximab/Placebo treatment and for the remainder of the study. [If receiving IVIg, patients will be allowed to receive the ongoing non-immunosuppressive drugs used to treat SPS including Diazepam, Neurontin or Baclofen. The dose of these drugs will remain stable throughout the study and unchanged for 6 weeks prior to enrollment.]
- 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.
Show all 9Show fewer
- Adequate bone marrow, renal, and liver function: ANC greater than 1000/mm(3), BUN/Cr in normal range for age.
- Patients with Diabetes (Type II) will be allowed to participate because up to 40% of SPS patients have Diabetes.
- Patients with a history of controlled epilepsy will be allowed to participate because up to 5% of SPS patients have mild epilepsy which is easily controlled.
Who cannot join
- Immunosuppressive drug therapy for SPS at the time of or 6 weeks prior to enrollment and for the remainder of the study. 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.
- Any medical or social condition that precludes follow-up visits.
- Any active malignancy or any history of a hematogenous malignancy or lymphoma. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are treated prior to enrollment.
- History of a coagulopathy or patients requiring anticoagulation.
- 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.
Show all 17Show fewer
- Chronic and severe symptomatic hypotension (SBP less than 100 mmHg).
- Chronic liver disease or alcoholism.
- Any condition, including active infections, that would likely increase the risk of protocol participation or confuse the understanding of the data.
- 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.
- LABORATORY EXCLUSION CRITERIA (AT SCREENING):
- Hemoglobin: less than 7.0 gm/dL.
- Platelets: less than 100,000/mm.
- AST or ALT greater than 2.5 x Upper Limit of Normal unless related to primary disease.
- Positive Hepatitis B or C serology (Hep Surface antigen and Hep C hepatitis C antibody).
- Positive HIV.
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: Efficacy of Rituximab in Patients With Stiff Person Syndrome With Anti-GAD Antibodies: A Randomized Placebo-Controlled Trial
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.
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 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.
- Conditions
- Stiff Person Syndrome
- Being tested
- Rituximab, rituximab or placebo
- Keywords
- RITUXAN, GABA, B Cells, Humanized Monoclonal Antibodies, GAD, Stiff Person Syndrome, SPS
- Medical subject headings
- Stiff-Person Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
rituximab or placeboDrug
Also called Rituxan
A fixed dose of Rituximab or placebo 1GM on Day 1 and 1GM on day 15 (+/- 2 days)
| Study group | Role | What they receive |
|---|---|---|
| Rituximab or placebo | Experimental | Rituximab or placebo is administered through intravenous access on day 1 and again on day 15 (+/- 2 days) Receives: Drug: Rituximab; Drug: rituximab or placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the efficacy, safety of the chimeric monoclonal antibody Rituximab to deplete B lymphocytes in patients with Stiff Person Syndrome with high anti-GAD antibodies.
Measured: 2 Years
Secondary outcomes (1)
The Heightened Sensitivity Scale will be used as a secondary outcome measure.
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2004 (estimated)
- Study startSep 2004
- Primary completionJul 2007
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Stiff Person SyndromeStudies 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
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00091897
- Sponsor's protocol ID
- 040287
- Other IDs
- IND-BB: 11844, 04-N-0287
- Status last verified
- Aug 2011
- First submitted
- 18 Sep 2004
- Last updated
- 31 Aug 2011
- Results posted
- No
Publications
Dalakas MC, Fujii M, Li M, McElroy B. The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology. 2000 Nov 28;55(10):1531-5. doi: 10.1212/wnl.55.10.1531.
PubMed 11094109Dalakas MC, Li M, Fujii M, Jacobowitz DM. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology. 2001 Sep 11;57(5):780-4. doi: 10.1212/wnl.57.5.780.
PubMed 11552003Levy LM, Dalakas MC, Floeter MK. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med. 1999 Oct 5;131(7):522-30. doi: 10.7326/0003-4819-131-7-199910050-00008.
PubMed 10507962
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Rituximab in Patients With Stiff Person Syndrome With Anti-GAD Antibodies: A Randomized Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT00091897
- Acronym / sponsor ID
- 040287
- Conditions
- Stiff Person Syndrome
- Keywords
- RITUXAN, GABA, B Cells, Humanized Monoclonal Antibodies, GAD, Stiff Person Syndrome, SPS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Sep 2004
- Primary completion
- Jul 2007 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 20 Sep 2004 (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 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab or placebo | Experimental | Drug: Rituximab, Drug: rituximab or placeboRituximab or placebo is administered through intravenous access on day 1 and again on day 15 (+/- 2 days) |
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Stiff Person Syndrome with elevated anti-GAD antibody titers.
- Between 25 to 80 years of age.
- Willingness to stop IVIg therapy 6 weeks prior to Rituximab/Placebo treatment and for the remainder of the study. [If receiving IVIg, patients will be allowed to receive the ongoing non-immunosuppressive drugs used to treat SPS including Diazepam, Neurontin or Baclofen. The dose of these drugs will remain stable throughout the study and unchanged for 6 weeks prior to enrollment.]
- Willingness and legal ability to give and sign informed study consent.
- Willingness to travel to NIH for scheduled protocol studies and treatment.
Key exclusion criteria (17 listed)
- Immunosuppressive drug therapy for SPS at the time of or 6 weeks prior to enrollment and for the remainder of the study. 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.
- Any medical or social condition that precludes follow-up visits.
- Any active malignancy or any history of a hematogenous malignancy or lymphoma. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are treated prior to enrollment.
- History of a coagulopathy or patients requiring anticoagulation.
- 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.
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 | Rituximab or placebo |
| rituximab or placeboAlso: RituxanA fixed dose of Rituximab or placebo 1GM on Day 1 and 1GM on day 15 (+/- 2 days) | Drug | Rituximab or placebo |
Primary outcome
To evaluate the efficacy, safety of the chimeric monoclonal antibody Rituximab to deplete B lymphocytes in patients with Stiff Person Syndrome with high anti-GAD antibodies.
Time frame: 2 Years
1 secondary outcome
The Heightened Sensitivity Scale will be used as a secondary outcome measure.
Time frame: 2 Years
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 31 Aug 2011.
- Background: PubMed 11094109Dalakas MC, Fujii M, Li M, McElroy B. The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology. 2000 Nov 28;55(10):1531-5. doi: 10.1212/wnl.55.10.1531.
- Background: PubMed 11552003Dalakas MC, Li M, Fujii M, Jacobowitz DM. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology. 2001 Sep 11;57(5):780-4. doi: 10.1212/wnl.57.5.780.
- Background: PubMed 10507962Levy LM, Dalakas MC, Floeter MK. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med. 1999 Oct 5;131(7):522-30. doi: 10.7326/0003-4819-131-7-199910050-00008.
Related trials for Stiff Person Syndrome
Not yet recruitingPhase 1/2
A Safety and Efficacy Study Evaluating CTX112 in Subjects With Refractory Neurologic Autoimmune Disease
Progressive Multiple Sclerosis (PMS), Neuromyelitis Optica
Not yet recruitingPhase 3
A Study Investigating Intravenous Human Normal Immune Globulin 10% in Adults With Stiff Person Syndrome
Stiff Person Syndrome
RecruitingPhase 2/3
VYVGART (Hytrulo) in Patients With Stiff Person Syndrome (SPS)
Stiff Person Syndrome
RecruitingObservational study
Biomarkers in Autoimmune Disease of Nervous System
Autoimmune Diseases of the Nervous System, Neuromyelitis Optica Spectrum Disorder
Enrolling by invitationPhase 1
A Phase 1 Study of Prulacabtagene Leucel (Prula-cel, Formerly ADI-001) in Autoimmune Disease
Lupus Nephritis, Autoimmune Diseases
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 Stiff Person Syndrome, 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 9 inclusion and 17 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 31 Aug 2011. 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?
To evaluate the efficacy, safety of the chimeric monoclonal antibody Rituximab to deplete B lymphocytes in patients with Stiff Person Syndrome with high anti-GAD antibodies. (time frame: 2 Years). 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 NCT00091897, which also lists 3 linked publications.
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 31 Aug 2011.