Clinical Trial: Genetic Determinants of Ankylosing Spondylitis Severity


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Sponsored by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by:	Warren G Magnuson Clinical Center (CC)

This study will explore how genes may influence the severity of ankylosing spondylitis, a form of arthritis that affects the spine. Patients have inflammation of the joints of the spine, which may cause the bones of the spine to fuse, resulting in difficulty performing daily activities.

Patients who developed ankylosing spondylitis after age 16 and have had the disease for less than 20 years may be eligible for this study. The onset of disease is dated to the first appearance of symptoms of inflammatory low back pain or restricted spinal motion. Patients with a spondyloarthropathy other than AS may not participate. Candidates will be screened with a medical history and physical examination, blood test, and review of their medical records. They will also complete a questionnaire about their disease symptoms and medical history.

Those enrolled in the study will return to the NIH Clinical Center at 2, 6, 10, 14, 18, 22, and 26 months after screening for examination of the joints, measurement of flexibility of the spine, and a blood test. They will also complete a symptoms assessment questionnaire. At the first study visit (2 months after screening), x-rays will be taken of the pelvis, lower back, and neck, if recent X-rays (within 1 year) are not available. These x-ray studies will be repeated on all patients at their last visit (26 months after screening).

Condition
Ankylosing Spondylitis

The susceptibility to ankylosing spondylitis (AS) is largely genetically determined. Recent studies suggest that the severity of AS is also influenced by genetic factors. The goal of this study is to identify genes that influence the severity of AS. We hypothesize that genetic markers of susceptibility, including human leukocyte antigen (HLA) polymorphisms, and genes that regulate inflammation and bone formation, influence the severity of AS.

In this prospective longitudinal study, we will test the association of several genetic markers with the severity of AS in 200 patients. Each patient will have had AS for less than 20 years. Measures of AS severity will be patient-reported pain and stiffness, functional disability, patient and physician global assessments, joint counts, number of tender entheses, spinal mobility, and laboratory measures of inflammation. These measures will be assessed every 4 months for 2 years. We will also evaluate new laboratory tests as measures of the activity of AS.

Identifying genetic markers that are associated with differences in the severity of active inflammation in AS will enhance our understanding of the pathogenesis of this disease by suggesting mechanisms and pathways involved in the development of long-term damage. In a separate but related protocol, we will assess genetic markers associated with spinal fusion and long-term functional disability in patients with AS.

INCLUSION CRITERIA:
Participants will:
1. have been diagnosed with AS by the modified New York criteria.
2. have had AS for less than 20 years. The duration of AS will be dated from the time of onset of symptoms of inflammatory low back pain or restricted spinal motion.
3. be able to read English.
EXCLUSION CRITERIA:
Potential participants will be excluded if:
1. onset of AS was at age 16 or younger.
2. have a spondyloarthropathy other than AS.
3. are unable to provide informed consent.
4. anticipate not being available or able to comply with the schedule of study visits.
Children will necessarily be excluded.