Genetic Determinants of Ankylosing Spondylitis Severity - Longitudinal Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ) Identifier:
First received: March 21, 2003
Last updated: May 11, 2016
Last verified: January 2016

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).

Ankylosing Spondylitis

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Genetic Determinants of Ankylosing Spondylitis Severity - Longitudinal Study

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 2999997
Study Start Date: March 2003
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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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. 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.

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 chapters of the Arthritis Foundation and the Spondylitis Association of America. Former participants in our AS protocols will be notified of this study by letter.

Study of first-degree relatives:

Participants will be:

  1. Parent, sibling, or child (age 18 or older) of an enrolled subject.
  2. Able to provide informed consent.

Family members may by asymptomatic or have signs or symptoms of AS or a condition in the spondyloarthropathy family. There is no requirement for a minimum number of members per family to be eligible for participation.

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. To ensure a sufficient sample of patients with active inflammation, enrollment in the study will be monitored so that at least 80 patients will be included who have an ESR of 40 mm/hr or higher at the screening visit or visit 1, or who have an elevated serum C-reactive protein level at visit 1.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00056719

Contact: Nancy A Spencer (301) 827-0186
Contact: Michael M Ward, M.D. (301) 496-7263

United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048-1804
Contact: Kristina Van Citters    301-423-2422   
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
United States, Texas
University of Texas Health Science Center - Houston Recruiting
Houston, Texas, United States
Contact: Laura Diekman    713-500-6852   
University of Queensland Recruiting
Brisbane, Australia
Contact: Linda Bradburry    +61 (0)7 3343 7077   
Sponsors and Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: Michael M Ward, M.D. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  More Information

Additional Information:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ) Identifier: NCT00056719     History of Changes
Other Study ID Numbers: 030131  03-AR-0131 
Study First Received: March 21, 2003
Last Updated: May 11, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Ankylosing Spondylitis

Additional relevant MeSH terms:
Bone Diseases, Infectious
Spondylitis, Ankylosing
Bone Diseases
Joint Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies processed this record on May 22, 2016