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Assessment of SpondyloArthritis Society (ASAS) Classification and Diagnostic Criteria for Early Axial Spondyloarthritis (SpA)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified February 2013 by J. Sieper, Charite University, Berlin, Germany.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT00328068
First Posted: May 19, 2006
Last Update Posted: February 13, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
J. Sieper, Charite University, Berlin, Germany
  Purpose

Background:

Existing criteria for AS/SpA such as mod. New York, ESSG, or Amor criteria for classification and/or diagnosis of spondyloarthritis have limitations when applied to early disease. Moreover, MRI is not part of any of the established criteria and the precise role of MRI in early axial disease has not been fully defined yet. Even less is known about sacroiliac (SI) changes in SpA patients with peripheral symptoms. A pilot study using data from 'paper patients' led to new candidate criteria for early spondyloarthritis. Subsequently, the members of the ASAS International Working Group decided to conduct a prospective multi-centre study to evaluate (validate) the new candidate criteria, and to assess their performance as diagnostic criteria.

Aims of the study:

  1. To evaluate the new candidate criteria for axial SpA in a multi-centre setting.
  2. To assess the potential role of the new candidate criteria to be used as diagnostic criteria. To accomplish this, inclusion of consecutive and undiagnosed patients is mandatory as are longer periods of follow-up .
  3. To compare criteria encompassing the whole group of SpA such as ESSG and Amor criteria against criteria which are tailored to either predominant axial disease or predominant peripheral disease. To accomplish this, both patients with predominant axial disease (back pain) but also patient with predominant peripheral disease (arthritis/enthesitis) will be included.

Condition
Spondyloarthritis Spondylarthropathy Spondylitis, Ankylosing

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective, International, Multi-centre Study on ASAS Classification Criteria for SpA

Resource links provided by NLM:


Further study details as provided by J. Sieper, Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Diagnosis of Spondyloarthritis [ Time Frame: 2 years ]

Secondary Outcome Measures:
  • Patients with a retained diagnosis of spondyloarthritis after follow-up [ Time Frame: 2-5 years ]

Biospecimen Retention:   Samples With DNA
DNA and RNA will be collected in selected centres for analysis of candidate gene variants in ankylosing spondylitis/ spondyloarthritis. Serum and plasma sample will be collected for biomarker analysis with special focus on markers of bone metabolism

Estimated Enrollment: 992
Study Start Date: July 2006
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Back pain / peripheral arthritis
Patients with chronic back pain of unknown origin and onset of back pain <45 years of age or patients with peripheral arthritis / enthesitis / dactylitis of unknown origin and onset <45 years of age

  Hide Detailed Description

Detailed Description:

Background:

Existing criteria for AS/SpA such as mod. New York, ESSG, or Amor criteria for classification and/or diagnosis of spondyloarthritis have limitations when applied to early disease. Moreover, MRI is not part of any of the established criteria and the precise role of MRI in early axial disease has not been fully defined yet. Even less is known about sacroiliac (SI) changes in SpA patients with peripheral symptoms. A pilot study using data from 'paper patients' led to new candidate criteria for early spondyloarthritis. Subsequently, the members of the ASAS International Working Group decided to conduct a prospective multi-centre study to evaluate (validate) the new candidate criteria, and to assess their performance as diagnostic criteria.

Aims of the study:

  1. To evaluate the new candidate criteria for axial SpA in a multi-centre setting.
  2. To assess the potential role of the new candidate criteria to be used as diagnostic criteria. To accomplish this, inclusion of consecutive and undiagnosed patients is mandatory as are longer periods of follow-up .
  3. To compare criteria encompassing the whole group of SpA such as ESSG and Amor criteria against criteria which are tailored to either predominant axial disease or predominant peripheral disease. To accomplish this, both patients with predominant axial disease (back pain) but also patient with predominant peripheral disease (arthritis/enthesitis) will be included.

Participating centres:

All ASAS members working in clinical practice are invited to participate in the study. More than one ASAS member/ rheumatologist per centre may participate.

Inclusion criteria:

Include newly referred patients if

  • onset of symptoms (back pain / arthritis / enthesitis) < 45 years and
  • undiagnosed* disease with the following symptoms:

    • chronic back pain (duration of back pain more than 3 months)
    • or / and peripheral arthritis (asymmetric arthritis / predominantly of the lower limbs)
    • or / and enthesitis
    • or / and dactylitis

      • Definition of 'undiagnosed':

The patient is being referred to your department because of chronic back pain, arthritis, enthesitis or dactylitis but has not been diagnosed confidently before by the referring physician/rheumatologist as having SpA or as definitely not having SpA. If the referring physician/GP/rheumatologist suspects SpA but is not certain about it, the patient is considered as undiagnosed.

Endpoints of the study:

  • Primary endpoint: the diagnosis made by the rheumatologist (ASAS member) after the diagnostic work-up. This expert diagnosis serves as preliminary gold standard against which the various criteria will be compared. Final gold standard will be the outcome (diagnosis) after long-term follow up.
  • Secondary endpoints: the diagnosis made by the rheumatologist at 2 and 5 years, respectively, after the first assessment. Thus, all patients should be invited to follow-up visits after 2 and 5 years, respectively.

Further study rules:

  • Include all newly referred patients strictly consecutively as long as they meet the inclusion criteria.
  • The decision to include a patient should be based solely on the fulfilment of the inclusion criteria, and should be made ideally before you make the final diagnosis (prospective study design).
  • Patients who have been diagnosed confidently and correctly by the referring physician prior to being referred to your department cannot be included in the study.
  • If you are unable to perform MRIs in your clinical setting you cannot include patients with undiagnosed chronic back pain.
  • If you want to include patients with undiagnosed chronic back pain, perform MRI of sacroiliac (SI) joints in the first 10 patients with axial SpA and in the first 10 patients with non-SpA related (mechanical) back pain. In subsequent patients you may perform MRIs as needed on clinical grounds. (Explanation: a minimum number of MRIs in both SpA and non-SpA patients from several centres is necessary to obtain reliable results on sensitivity and specificity of MRI in early axial SpA.)
  • MRI of SI joints in patients with peripheral symptoms only will be performed in selected centres (centres already indicated whether this will be possible).
  • MRI results will be taken as provided by the local centre (either read by the radiologist or rheumatologist, whoever has greater experience). Results will be categorized into 'presence or absence of active inflammatory lesions compatible with SpA', and 'presence or absence of chronic lesions compatible with sacroiliitis/spondylitis'. (Selected centres will be invited to send us their MRIs for validation of locally performed readings (the intention is to increase the quality of data).
  • Plain radiographs of the SI joints and lumbar spine are mandatory in all patients with undiagnosed chronic back pain. Previously taken radiographs are acceptable if they are not older than 6 months. Results are taken as provided locally either by the radiologist or rheumatologist, whoever has greater experience.
  • At the end of the diagnostic work up, a preliminary diagnosis must be made by the ASAS rheumatologist as is done in usual daily clinics. It is not important to be absolutely confident about the diagnosis at this stage since this i) reflects daily practice, and ii) the level of confidence with the diagnosis will be assessed as well. (It is more important to include all patients consecutively in your centre in order to avoid any selection bias.) The senior ASAS member should supervise other physicians experienced in SpA in her/his department who participate in the study.
  • Patients with peripheral symptoms should be included if they meet the inclusion criteria. Patients with peripheral symptoms and a history of chronic back pain or with concomitant chronic back pain must undergo radiographic examination of the SI joints. Patients with non-specific musculoskeletal pain or arthralgia (without arthritis) only cannot be included.

Data documentation:

The results of the clinical history, physical examination, blood tests, radiographs, and MRIs, and the diagnosis will be entered into the CRF locally by the ASAS member during/after the diagnostic work-up. The diagnosis will be made by the local rheumatologist (ASAS member or an experienced colleague at the centre). The completed CRF should be sent to the coordinating centre (Berlin) for data check and data entry. A copy of the CRF should remain locally at the study centre. The name, date of birth, address, and telephone number must also be kept locally in the centre since follow-up assessments after 2 years and after 5 years are planned.

Sample size and inclusion period:

It is estimated that about 400-500 patients with SpA (ca 250-300 axial and 150-200 peripheral SpA) with complete data sets are needed to allow for a reliable comparison of new candidate criteria with established criteria. Since the prevalence of SpA among newly referred patients with unclear diagnoses varies from centre to centre any calculation of the control group size (and thus total sample size) is bound to be inaccurate. Therefore, the proposal is that each centre recruits as many consecutive patients as possible until indicated by the study coordinators to stop inclusion. The study coordinators can adequately terminate the inclusion period only if the completed CRFs are sent within a reasonably short period of time (< 2 weeks) to the coordinating centre. Data entry and data analysis will be done at the coordinating centre.

DNA/RNA-analysis and biomarker analysis:

In addition to the clinical study which aims to arrive at new classification and diagnostic criteria, two groups of researches will perform laboratory experiments in patients from selected centres: Genetic polymorphisms and gene products (RNA) which are potentially associated with spondyloarthritis will be analysed by Prof. Matthew Brown in Brisbane, Australia. A second group of researchers (Prof. Walter Maksymowych, Canada, Prof. Mikkel Ostergaard, Denmark, Prof. Rob Inman, US, and Prof. David Yu, US) will analyse several biomarkers such as cartilage break-down or bone formation proteins in serum and/or plasma. Data from both experimental projects may be of potential diagnostic value in the future and/or may reveal novel insights into pathophysiological mechanisms of spondyloarthritis.

Longterm follow-up:

A second follow-up visit of all patients 2 years after the first encounter and also 5 years after the first encounter is highly warranted since diagnoses may change over time and the final diagnosis after long-term follow up is the most important gold standard. Thus, a record containing the names, addresses, and phone numbers of all patients included in the study must be stored locally at the study site. The patient is best informed at the first visit that a follow-up assessments 2 and 5 years later are envisaged.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with chronic back pain of unknown origin or peripheral arthritis / enthesitis / dactylitis of unknown origin who are referred to a rheumatologist for diagnostic work-up
Criteria

Inclusion Criteria:

Include newly referred patients if:

  • Onset of symptoms (back pain/arthritis/enthesitis) < 45 years
  • Undiagnosed disease with the following symptoms:

    • chronic back pain (duration of back pain more than 3 months)
    • and/or peripheral arthritis (asymmetric arthritis/predominantly of the lower limbs)
    • and/or enthesitis
    • and/or dactylitis

Exclusion Criteria:

  • No symptoms such as specified in inclusion criteria: back pain, arthritis, enthesitis
  • Definite diagnosis
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00328068


Contacts
Contact: Martin Rudwaleit, MD +49(0)30-8445 ext 4535 martin.rudwaleit@charite.de
Contact: In-Ho Song, MD +49(0)30-8445 ext 4795 in-ho.song@charite.de

  Show 35 Study Locations
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Principal Investigator: Martin Rudwaleit, MD Universitatsmedizin Berlin, Charité Campus Benjamin-Franklin, Med. Clinic I, Rheumatology, Hindenburgdamm 30, 12200 Berlin, Germany
Principal Investigator: Joachim Sieper, MD Charité Universtaetsmedizin Berlin
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: J. Sieper, Prof., Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT00328068     History of Changes
Other Study ID Numbers: ASAS-class-crit-1
First Submitted: May 18, 2006
First Posted: May 19, 2006
Last Update Posted: February 13, 2013
Last Verified: February 2013

Keywords provided by J. Sieper, Charite University, Berlin, Germany:
ASAS classification
ASAS diagnostic criteria
spondyloarthritis
spondyloarthropathy
spondylitis, ankylosing
modified New York criteria for AS
ESSG criteria for SpA
Amor criteria for SpA
arthritis
enthesitis
magnetic resonance imaging

Additional relevant MeSH terms:
Spondylitis
Spondylarthritis
Spondylitis, Ankylosing
Spondylarthropathies
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Arthritis
Joint Diseases
Ankylosis