Clinical trial NCT00056719: Genetic Determinants of Ankylosing Spondylitis Severity - Longitudinal Study
Official title: Genetic Determinants of Ankylosing Spondylitis Severity - Longitudinal Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ankylosing Spondylitis
Keywords: Arthritis
Spondylarthropathy
Spine
Hereditary
Disability
Natural History
Ankylosing Spondylitis
Spondyloarthropathy
Spondyloarthritis
AS
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2003-03-20
Enrollment: 299
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: identify genes assoc. w/ severity of AS@@@

Brief summary: 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 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 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after screening for examination of the joints, measurement of flexibility of the spine, and a blood test. They will also complete symptoms assessment and coping questionnaires. At the first study visit (screening visit), 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 every two years during the study (at 24 and 48 months after screening).

Detailed description: 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. Approximately 700 patients will be included. 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 6 months for 5 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.

Eligibility criteria: * INCLUSION AND EXCLUSION CRITERIA:

Participants will:

1. have been diagnosed with AS by the modified New York criteria.
2. be able to read English or Spanish

Potential participants will be excluded if:

1. have a spondyloarthropathy other than AS.
2. are unable to provide informed consent.
3. anticipate not being available or able to comply with the schedule of study visits.

Study entry is not limited by sex or ethnic origin. Children will necessarily be excluded because spondyloarthropathy developing before age 16 is considered a form of juvenile idiopathic arthritis, and because different age-appropriate measures of functional disability and pain would be needed.

Participants will be recruited by physician referral and self-referral. Information about the study will be mailed to local rheumatologists and posted on the NIH website. Notices will also be sent to local rheumatologists and posted on the NIH website. Notices will also be sent to local chapters of the Arthritis Foundation and the Spondylitis Association of America.

The accrual ceiling will be unlimited. Approximately 700 patients will be enrolled from all study sites. Approximately 150 patients will be recruited at the NIH. Other sites participating in this study are Cedars-Sinai Medical Center, Los Angeles, CA; the University of California-San Francisco and University of Texas-Houston Health Sciences Center.

Primary outcomes:
measure: identify genes assoc. w/ severity of AS
timeFrame: 10 years
Secondary outcomes:
measure: identify genetic polymorphisms of AS
measure: Changes in symptoms of AS over time
measure: Genetic var. in 1st degree rel. of AS pt
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
name: Robert A Colbert, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boyer GS, Templin DW, Bowler A, Lawrence RC, Everett DF, Heyse SP, Cornoni-Huntley J, Goring WP. A comparison of patients with spondyloarthropathy seen in specialty clinics with those identified in a communitywide epidemiologic study. Has the classic case misled us? Arch Intern Med. 1997 Oct 13;157(18):2111-7.
citation: Mau W, Zeidler H, Mau R, Majewski A, Freyschmidt J, Stangel W, Deicher H. Clinical features and prognosis of patients with possible ankylosing spondylitis. Results of a 10-year followup. J Rheumatol. 1988 Jul;15(7):1109-14.
citation: Amor B, Santos RS, Nahal R, Listrat V, Dougados M. Predictive factors for the longterm outcome of spondyloarthropathies. J Rheumatol. 1994 Oct;21(10):1883-7.