Clinical trial NCT00344448
Conditions: Sjogren's Syndrome
Keywords: Adhesion Molecule Interventional Study Immunomodulation Autoimmunity Sjogren Syndrome SS
Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)
Start date: 2006-06-01; Completion date: 2009-01-01
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will examine the effect of the drug Raptiva (efalizumab) in patients with Sjögren's syndrome (SS), an autoimmune disease affecting the glands producing saliva \& tears. The cause of SS is not known, but inflammation plays an important role. Raptiva is approved by the Food and Drug Administration to treat psoriasis, an inflammatory skin disease. Patients 18 years of age \& older with SS may be eligible for this study. Candidates are screened with a history \& physical examination, chest x-ray, and oral \& eye examinations.

Participants are randomly assigned to receive either Raptiva or placebo (an inactive substance that looks like Raptiva) for the first 3 months of the study. For the next 3 months, all participants receive Raptiva. Both Raptiva \& placebo are injected under the skin once a week. Evaluation during treatment \& for 2 months after treatment as follows:

Full comprehensive evaluations (beginning of the study, at weeks 13 \& 25 and 2 months after treatment ends):

* Physical examination \& blood draw.
* Saliva collection done in two ways: 1) suctions cups connected to collection tubes are placed over the salivary gland ducts in the mouth and under the tongue; and 2) a sour-tasting liquid is applied to the top \& sides of the tongue at 30-second intervals to stimulate saliva production.
* Eye exam for tear gland function.
* Questionnaires about mouth \& eye dryness, energy level and overall well-being.
* Lip biopsy (screening \& week 13 visits only). A few minor salivary glands are removed for examination under a microscope. The lower lip is numbed, a small cut is made on the inside of the lip, and several glands are removed. The cut is closed with a few stitches that are removed after 5 to 7 days.
* Magnetic resonance imaging of the parotid glands (salivary glands near the ear) at weeks 1, 13 and 25. The patient lies on a stretcher that is moved into the scanner (a metal cylinder containing a strong magnetic field). The head is held in place during the scan. The study lasts about 90 minutes.
* Short evaluations at weeks 3, 5, 9, 15, 17, 21 and 1 month after treatment ends.
* Medical history \& physical examination, blood draw, evaluation for changes in symptoms and side effects, review of current medications at weeks 3, 9, 15 and 21.
* Laboratory tests, evaluation for changes in symptoms and side effects, review of current medications, saliva collection without the sour liquid and short evaluation of tear production at weeks 5 and 17.
* Blood tests at week 29

Detailed description:
The LFA-1/ICAM-1 interaction is important in migration of lymphocytes to inflammatory sites, T-lymphocyte activation, antigen presentation, and maintaining the integrity of the immunologic synapse. In both murine and human Sjogren's Syndrome, increased expression of LFA-1 was found on activated lymphocytes, and increased expression of ICAM-1 was present on the activated endothelial cells in the diseased salivary and lacrimal glands. In animal models, blockade of the LFA-1/ICAM-1 interaction resulted in reduction of glandular inflammation.

Raptiva (efalizumab) is a recombinant humanized monoclonal antibody that binds to human CD11a, the alpha-subunit of Leukocyte Function Antigen-1 (LFA-1) and inhibits the LFA-1/ICAM-1 interaction. Raptiva is an FDA-approved medication for treatment of mild-to-moderate psoriasis.

In this pilot, proof of concept, randomized, double-blind, placebo-controlled study, up to 25 patients with Sjogren's syndrome may be enrolled. In the first, double-blind phase of the study, patients will be randomized and treated with weekly subcutaneous (SC) injections of either Raptiva (1mg/kg) or placebo for 12 weeks. In the second open label phase, all patients will be treated with weekly SC injections of Raptiva (1mg/kg) for another 12 weeks and then followed for an additional 8 weeks. Safety will be evaluated using standard clinical and laboratory parameters. To assess the potential effect of Raptiva on Sjogren's syndrome, minor salivary gland biopsy, oral and ocular evaluations, and measurements of surrogate markers of inflammation will be compared between the Raptiva and placebo treated groups before and after the treatment. Patients who either do not tolerate the drug or have worsening in their disease activity will be withdrawn from the protocol.

If Raptiva is well tolerated in this study and the treatment is associated with improvement in clinical parameters of Sjogren's Syndrome, further large studies of efficacy are planned.

Arms: arm 1: At the beginning of the first (week 1) and second (week 13) phases, all patients will receive reduced dose of the study medication determined at 0.7 mg/kg/week. During all the subsequent administrations, all patients will receive full dose of the study medication determined at 1 mg/kg/week. arm 2: Weekly subcutaneous injection of a placebo (formulated to match the commercial vial of Raptiva in appearance and content except for the active ingredient) for the first 12 weeks of the study.
Interventions: intervention 1: Raptiva
Intervention descriptions: intervention 1: During the first phase of the study, subjects are randomized in a double blind fashion to receive weekly subcutaneous injections of efalizumab (Raptiva) or placebo (weeks 0-12). The second 12 weeks long phase is open label with all subjects receiving weekly subcutaneous injections of efalizumab.

Protocol documents: