Genetic Determinants of Ankylosing Spondylitis Severity - Longitudinal Study

• ClinicalTrials.gov Identifier: NCT00056719
• Recruitment Status: Completed
• First Posted: March 20, 2003
• Last Update Posted: January 31, 2023
• Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) )

Study Description

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).

Condition or disease
Ankylosing Spondylitis

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 299 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Genetic Determinants of Ankylosing Spondylitis Severity - Longitudinal Study
• Actual Study Start Date: June 19, 2003

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. identify genes assoc. w/ severity of AS [ Time Frame: 10 years ]
   identify genes assoc. w/ severity of AS

Secondary Outcome Measures :

1. identify genetic polymorphisms of AS
2. Changes in symptoms of AS over time
3. Genetic var. in 1st degree rel. of AS pt

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

identify genes assoc. w/ severity of AS@@@

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.

Contacts and Locations

Locations

United States, Maryland

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

• Principal Investigator: Robert A Colbert, M.D.; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

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.

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.

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.

• Responsible Party: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• ClinicalTrials.gov Identifier: NCT00056719
• Other Study ID Numbers: 030131; 03-AR-0131
• First Posted: March 20, 2003
• Last Update Posted: January 31, 2023
• Last Verified: January 27, 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: .not yet known

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ):

Arthritis; Spondylarthropathy; Spine; Hereditary; Disability; Natural History; Ankylosing Spondylitis; Spondyloarthropathy; Spondyloarthritis; AS

Additional relevant MeSH terms:

Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Spinal Diseases; Arthritis; Joint Diseases; Spondylarthropathies; Ankylosis