Imaging Biomarkers in Crohn's Associated Spondyloarthritis

NCT02709694 | Completed Results

• 1 other identifier: 2015-491
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

In patients with Crohn's Disease, symptoms of inflammatory back pain (IBP) precede changes on plain X-rays by years, and MRI changes of axial inflammation precede development of X-ray changes. Sacroiliitis on MRI without x-ray changes (i.e.Non radiographic SpA) is a valid diagnostic criterion for Spondyloarthritis (SpA) and leads to earlier diagnosis of SpA in patients with IBP. It is unclear when MRI changes occur, and if they precede clinical symptoms of IBP. There are reports of asymptomatic sacroiliitis noted on MRI in Crohn's patients. This is important, as MRI evidence of inflammation may be the first sign of incipient SpA. Inflammation in other regions of the axial skeleton in SpA patients has also been documented, but its significance is unknown. The prospect of undiagnosed and untreated inflammation is concerning, as it can lead to significant morbidity. Moreover, relationship between MRI evidence of axial inflammation-likely a proxy for systemic inflammation- and patient reported outcomes (e.g. ASDAS-CRP= Ankylosing Spondylitis Disease Activity Score- C reactive protein, BASDAI= Bath Ankylosing Spondylitis Disease Activity Index, SF-12 = Short Form- 12, HBI= Hervey Bradshaw Index and PROMIS-29= Patient Reported Outcome Measurement Information System-29), has not been reported. Recent unpublished data from Dr. Longman's lab (collaborator) suggest a distinct intestinal dysbiosis in Crohn's associated SpA. But relationship between this microbiome and MRI changes is yet to be determined. Identifying inflammation earlier on MRI- in the absence of clinical symptoms will provide an opportunity to intervene early with available therapies, such as- biologics etc. Asymptomatic MRI changes could be a marker of underlying systemic inflammation- which is a risk factor for poor outcomes in Crohn's associated SpA. Studying association between whole spine MRI changes with patient reported outcomes) may facilitate informed clinical decision making to initiate targeted therapy to prevent progression of structural damage. Understanding microbial dysregulation in this population, and correlation with MRI changes, could lead to development of therapy targeted to restore intestinal symbiosis.

Conditions

Crohn's Disease; Spondyloarthritis

Outcome Measures

Primary Outcomes (4)

• Number of Participants With MRI Positivity- Global Assessment Positive

  MRIs were independently read and scored by 2 expert rheumatologists and 1 newly trained rheumatologist reader, blinded to any clinical information. MRIs were evaluated and scored for presence of bone marrow edema (BME) and structural lesions (erosion, fat metaplasia, backfill and ankylosis) using a validated scoring method originally derived from the Spondyloarthritis Research Consortium of Canada SIJ module. MRI was considered "positive" for presence of sacroiliitis if it met global evaluation, based on the reader's overall evaluation of presence or absence of sacroiliitis by taking into account the contextual signature of both active and structural SIJ lesions. For analysis, MRI positivity for sacroiliitis was defined based on majority-of-readers agreement (≥2 out of 3).

  one study visit

• Number of Participants With MRI Positivity- ASAS Positive

  Assessment of SpondyloArthritis international Society. Subjects are positive if they fulfill 4 out of following 5 back pain parameters: onset of symptoms \<40 years of age, insidious onset of pain, nocturnal pain, improvement with exercise and no improvement with rest.

  one study visit

• Number of Participants With MRI Positivity- SPACE Positive

  SpondyloArthritis Caught Early. Positivity based on presence of erosions and fat metaplasia.

  one study visit

• Number of Participants With MRI Positivity- Morpho Positive

  Positivity based on presence of bone marrow edema (BME) and/or erosion.

  one study visit

Secondary Outcomes (43)

• Number of Participants With Axial Spondyloarthritis Based on European Spondyloarthropathy Study Group (ESSG) Guidelines

  one study visit

• Number of Participants With Current Peripheral Arthritis

  one study visit

• Number of Participants With a History of Peripheral Arthritis

  one study visit

• Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

  one study visit

• Bath Ankylosing Spondylitis Metrology Index (BASMI)

  one study visit

Interventions

No intervention OTHER

No drug or device intervention. However, participants will receive MRI of their spine, answer questionnaires, provide clinical history as well as blood and stool sample. Joint exams will also be performed on all participants.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will biopsy proven Crohn's disease will be enrolled for the study. 50% (15 patients) will have symptoms of inflammatory back pain and 50% will not.

You may qualify if:

• Patients with biopsy proven Crohn's Disease
• % patients with inflammatory back pain and 50% without inflammatory back pain.
• Age 18 years and above
• English Speaking patients only

You may not qualify if:

• History of psoriasis, other inflammatory arthritis
• No exposure to biologic agent within the past six months (except Vedolizumab, which exerts its effect locally)
• \. Contraindication to MRI
• \. History of malignancy \<5 years in remission, (except for non-melanomatous skin cancer).
• \. Non English speaking
• \. Unable to comply with study protocol.
• \. Critically or terminally ill patients
• \. Pregnancy

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead
• Weill Medical College of Cornell University: collaborator

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Related Publications (20)

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  PMID: 23233285 BACKGROUND

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• Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, Morgan XC, Kostic AD, Luo C, Gonzalez A, McDonald D, Haberman Y, Walters T, Baker S, Rosh J, Stephens M, Heyman M, Markowitz J, Baldassano R, Griffiths A, Sylvester F, Mack D, Kim S, Crandall W, Hyams J, Huttenhower C, Knight R, Xavier RJ. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe. 2014 Mar 12;15(3):382-392. doi: 10.1016/j.chom.2014.02.005.

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood for C-reactive Protein and stool samples for fecal microbial 16s rRNA sequencing

MeSH Terms

Conditions

Crohn Disease; Spondylarthritis

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases

Results Point of Contact

• Title: Dr. Lisa Mandl
• Organization: Hospital for Special Surgery

mandll@hss.edu

(212) 774-2960

Study Officials

• Lisa Mandl, MD MPH

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: March 16, 2016
• Study Start: April 1, 2016
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2021
• Last Updated: October 25, 2021
• Results First Posted: October 25, 2021

Record last verified: 2021-09

Locations

US (1)