Stiff Person Syndrome Clinical Trial
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.
| Status | Completed |
| Enrollment | 24 |
| Est. completion date | May 2009 |
| Est. primary completion date | July 2007 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 25 Years to 80 Years |
| Eligibility |
- INCLUSION CRITERIA: 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. 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. EXCLUSION CRITERIA: 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. 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. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment
| 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, 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. — View Citation
Dalakas 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. — View Citation
Levy 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. Review. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | 2 Years | Yes | |
| Secondary | The Heightened Sensitivity Scale will be used as a secondary outcome measure. | 2 Years | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT00716066 -
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Phase 2 |