We are actively recruiting for patients with Sjögren’s syndrome. There are several ongoing clinical studies. If you wish to obtain more information on a study, to participate as a subject, or to refer patients, please click on the study number below. You may also go to NIH's clinical trials website. Once there, enter the word "Sjogren" and click on the Search button to search for relevant clinical trials. Depending on the protocol, participants can expect oral/dental, eye, general physical and rheumatological examinations, as well as blood and other tests. Eye examinations will be conducted at the Eye Clinic at the Clinical Center in collaboration with Dr. Janine Smith, an ophthalmologist who is conducting clinical trials on inflammatory disorders of the eye, including Sjögren’s syndrome.
84-D-0056 Screening Protocol for Salivary Gland Dysfunction
This study will evaluate patients with complaints of dry mouth to determine the cause and severity of their salivary gland dysfunction and their possible eligibility for other NIDCR protocols. Salivary secretions have antibacterial, lubricating, remineralizing, digestive, buffering and cleansing properties. Impaired function of these glands can cause an increase in tooth decay; a variety of oral hard and soft tissue changes, with painful, burning or ulcerated or oral mucosa; problems chewing, swallowing and speaking; and diminished taste and smell.
Patients with dry mouth complaints suggestive of salivary gland dysfunction may be eligible for this study.
Participants will have a complete medical and dental history. Saliva samples will be collected from the major salivary glands, which are located in the cheeks and under the tongue. Several blood samples will also be drawn for tests. Some patients will have a biopsy of the minor salivary glands, usually from inside the lower lip, to confirm or rule out the diagnosis of Sjögren’s syndrome and to determine the extent of changes in the salivary glands. An eye examination including a standard eye examination and a dry eye assessment is done. The ability to taste and smell may also be evaluated, and patients may have an ultrasound examination of their swallowing function.
99-D-0070 Natural History of Salivary Gland Dysfunction and Sjogren's Syndrome
Saliva plays a major role in maintaining oral health and comfort. Saliva is needed to moisten the mouth, to lubricate food for easier swallowing, to protect oral hard and soft tissues, to modulate oral microbial populations, to provide enzymes necessary to begin food breakdown for digestion, and to promote soft tissue repair and oral cleansing. Therefore, salivary dysfunction may result in numerous clinical conditions affecting oral and systemic health, comfort and quality of life. In particular, we will focus on individuals with Sjögren's syndrome, an autoimmune exocrinopathy that primarily affects the salivary and lacrimal glands. A number of unanswered questions remain concerning salivary involvement in this disorder. These include the rate of progression of secretory dysfunction, and related oral and systemic complications associated with xerostomia in autoimmune and non-autoimmune diseases, and B-cell dysregulation. Also, more precise estimates of the incidence of the lymphoma development are needed.
The purpose of this study is : 1) to allow careful follow-up of patients with defined salivary gland alterations so that the long term course and effects of Sjögren's syndrome (SS) on the oral cavity and systemic health in SS may be delineated; 2) to follow the development and progression of B-cell dysregulation in SS; 3) to follow subjects to establish whether those initially manifesting incomplete criteria for SS progress toward fully meeting the criteria.; 4) to refine diagnostic tests for SS, and to determine whether those subjects who meet the criteria for SS continue to do so; and 5) to develop intermediary outcome measures for SS based on long term outcomes (loss of tears and loss of stimulated salivary flow).
Patients will return every two years from the baseline visit for a full oral examination, salivary function assessment, clinical laboratory studies, and questionnaires concerning signs and symptoms of salivary gland dysfunction. These individuals will be patients with Sjögren's syndrome (SS), incomplete SS (patients who have some, but not all of the criteria for SS) or radiation-induced salivary gland hypofunction. We anticipate that many of these patients will also participate in therapeutic trials conducted within the branch.
06-D-0181 A Randomized, Placebo-Controlled Proof of Concept Study of Raptiva, a Humanized Anti-CD11a Monoclonal Antibody, in Patients with Sjogren's Syndrome
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 Sjögren’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 α-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 Sjögren’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 additional 8 weeks. Safety will be evaluated using standard clinical and laboratory parameters. To assess the potential effect of Raptiva on Sjögren’s syndrome, minor salivary gland biopsy, oral and ocular evaluations, 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 Sjögren’s Syndrome, further large studies of efficacy are planned.
94-D-0018 Salivary Evaluation in Normal Volunteers
Saliva is critical in maintaining oral health and comfort. Our laboratory has investigated several disorders of salivary glands. The purpose of this protocol is to obtain data from normal volunteers for comparison with data from patients with salivary dysfunction. We plan to utilize the Normal Volunteer Program to solicit paid participation from healthy adults. Study procedures are accomplished in two outpatient visits that include an interview, saliva collection, lip biopsy, clinical laboratory studies, dry eye examination, and lip biopsy follow up. These are routine diagnostic procedures and their possible hazards are minor. Biopsy specimens may be used in clinical and laboratory studies, such as in vitro biochemical analysis or in vivo transplantation.
08-D-0018 Clinical and Laboratory Evaluation of the Autonomic Nervous System in Primary Sjögren's Syndrome
The origin and mechanisms of Sjögren’s syndrome are not well understood. Prior research on the topic assumes that the autoimmune destruction of the affected glands leads to their diminished function and symptoms of dryness. The existing evidence however cannot completely explain the underlying disease-causing mechanisms of Sjögren’s syndrome for several reasons: 1) At least 20% of patients have no evidence of systemic autoimmunity; 2) No correlation between the extent of inflammation of the affected glands and the degree of dryness; 3) Loss of salivary function develops long before systemic autoimmunity in animal models of Sjögren’s syndrome; 4) No disease-causing auto-antibodies have been identified to date.
On the other hand all of the glands affected by Sjögren’s syndrome (salivary, lacrimal, sweat and other glands) are supplied with nerves by the autonomic nervous system. Disease or malfunction of the autonomic nervous system can mimic the major manifestations of Sjögren’s syndrome, such as dry mouth and dry eyes. Thus, we believe that impaired autonomic nervous system function is critical for the development of Sjögren’s syndrome and propose to study its function in patients with primary Sjögren’s syndrome compared with normal volunteers. This study is designed to comprehensively evaluate the function of the autonomic nervous system, using physiological, neuropharmacologic, neurochemical, and imaging approaches, to improve the understanding of disease mechanisms of Sjögren’s syndrome.
Updated January 18, 2008