Spondylitis, AnkylosingNCT03778515
Novel Quantitative MRI for Axial Spondyloarthritis
An observational study of Spondylitis, Ankylosing, run by The Cleveland Clinic at 1 site in United States.
Trial summary
This proposal aims to develop novel MR imaging and image processing techniques that will provide reliable and fully quantitative evaluation of inflammation, chronic structural changes and vascularity in patients with Ankylosing Spondylitis (AS). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Spondylitis, Ankylosing
- What is being tested?
- MRI
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2020to 31 Jul 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 15 patients will be recruited from the Ankylosing Spondylitis clinic at UCSF, and five patients will be recruited from Rheumatology clinic at the Cleveland Clinic. 10 patients with disease duration <= 10 years, and ten patients with disease duration > 10 years but without complete ankylosis. 5 healthy controls will be recruited for evaluating the measurement, with 2 from CCF and 3 from UCSF. The volunteers will be studied at baseline and 1-year follow up.
Who may be able to join
- Active AS meeting the modified New York criteria
- BASDAI ≥ 4
- Elevated C-Reactive Protein
- ≥ 18 years old
- Initiation of TNFi treatment with CZP
Who cannot join
- Previous treatment with more than one biologics
- Biologic treatment within six-months (no more than 20% of group (n=4) for patients with previous biologic treatment)
- Non-response to previous anti TNF treatment
- Fibromyalgia or other reasons for back pain
- Pregnant patients
- Patients on > 10mg of Prednisone per day
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
This proposal aims to develop novel MR imaging and image processing techniques that will provide reliable and fully quantitative evaluation of inflammation, chronic structural changes and vascularity in patients with Ankylosing Spondylitis (AS). The quantitative evaluation will be more objective and reproducible, more sensitive to subtle changes, and less time consuming, as compared to the current semi-quantitative evaluation. It will allow radiologists and rheumatologists to evaluate the inflammation and structural changes more reliably to improve early diagnosis and treatment response evaluation. The developed quantification tools can be disseminated to other research and clinical sites for retrospective and prospective data analysis, and used as outcome measures for future multi-center trials. The evaluation of vascularity will enhance Investigators understanding of disease pathophysiology and serve as a novel marker to improve investigators capability of evaluating and predicting treatment response in AS. The successful implementation will greatly assist clinicians to optimize individualized therapeutic strategies and ultimately improve patient care for AS.
Read the detailed description
There is a critical and unmet clinical need for non-invasive techniques that provide early diagnosis as well as reliable and sensitive evaluations of ongoing disease activity and treatment response in patients with axial spondyloarthritis (axSpA). Imaging plays a key role to fulfill this goal and there is an increasing trend of applying imaging techniques in the field of axSpA. However, current imaging techniques, including radiographs and MRI, are primarily limited to qualitative or semi-quantitative evaluations of disease activity and structural damage, which is very crude and subjective with considerable inter-reader variation, and has limited sensitivity of detecting early lesions as well as changes in inflammatory lesions beyond morphology of bone marrow edema after treatment. Furthermore, several recent studies reported data of inflammation (bone marrow edema), fatty deposition and new bone formation after TNF inhibitor (TNFi) treatment in patients with axSpA, suggesting a complex relationship between inflammation, bone formation, and suppression of the TNF pathway. These studies also call for differentiating edema for their characteristics (angiogenesis for example) and inflammation stages (acute and chronic), which will provide valuable insight on disease pathophysiology as well as on optimizing treatment for individual patients with axSpA.
The long-term goal is to develop novel quantitative MRI measures that will reliably assess both inflammation and structural damage, and predict treatment response, remission and disease progression in axSpA. Compared to current MRI grading systems, such quantitative measures may be used as more sensitive, specific, reliable and faster imaging markers for future trials, and eventually for clinical practice to improve patient management in axSpA. In this proposal, Investigators will focus on patients with clinically diagnosed active Ankylosing Spondylitis (AS) and will develop novel imaging and image processing techniques using 3 Tesla MRI. The specific aims are two-folds. Firstly, Investigators will develop methods that reliably quantify bone marrow edema (BME), fatty deposition (FD) and erosions; Secondly, Investigators will develop novel quantitative evaluation of perfusion and vascularity of BME (using dynamic Gd-enhanced MRI), which has not been investigated for axSpA in the literature.
Investigators will recruit 20 patients with active Ankylosing Spondylitis (AS) using the 1984 modified NY criteria. Fifteen patients will be recruited from the Ankylosing Spondylitis clinic at UCSF, directed by Dr. Lianne Gensler, and five patients will be recruited from Rheumatology clinic at the Cleveland Clinic by Dr. Elaine Husni. Drs. Gensler and Husni will also reach out to the other academic sites and the community private practices to recruit patients as needed who are starting TNF inhibitor therapy with CZP for their AS. Patients will be studied at baseline, 4-weeks and 48-weeks after initiation of TNFi treatment. Advanced quantitative MRI will be applied to evaluate early treatment response at 4-weeks, and long-term outcomes at 48-weeks. The central hypothesis is that quantitative MRI allows a fast, specific and reproducible evaluation of disease activity and structural changes in AS, and provides more superior diagnostic and prognostic capability compared to semi-quantitative MRI grading systems.
The successful implementation of the proposed study will make significant contributions to the research and clinical
- Conditions
- Spondylitis, Ankylosing
- Being tested
- MRI
- Keywords
- Axial, Spondyloarthritis, MRI, Ankylosing Spondylitis
- Medical subject headings
- Spondylitis, Ankylosing, Spondylarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIDiagnostic test
Observational Study of novel MR imaging and image processing techniques that will provide reliable and fully quantitative evaluation of inflammation, chronic structural changes and vascularity in patients with Ankylosing Spondylitis (AS).
| Study group | Role | What they receive |
|---|---|---|
| Cases - Ankylosing Spondylitis Cohort | 20 patients with ankylosing spondylitis (AS). Fifteen of these patients will be recruited from the Ankylosing Spondylitis clinic at the University of California, San Francisco. Five patients will be recruited from the Rheumatology clinic at the Cleveland Clinic. Observational with MRI. Receives: Diagnostic Test: MRI | |
| Controls - w/o Ankylosing Spondylitis | 5 patients without AS and with no history of any arthritis or lower back pain in this study. These 5 patients will make up the control group of the study, which means that they will provide a benchmark of comparison for the results investigators obtain from the active AS group. 2 of these 5 patients will be recruited from Cleveland Clinic, and 3 will be recruited from UCSF. Observational with MRI Receives: Diagnostic Test: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Volume of MRI bone marrow edema (in cm^3) from Baseline at 48-weeks
Fully quantitative evaluation of volume of bone marrow edema (in cm^3) will be developed and applied in the study. Volume of BME will be calculated in both SIJ and Spine in high-resolution MR images to evaluate the active inflammation in the patients.
Measured: Change from Baseline at 48-weeks
Change in MRI grading SPARCC from Baseline at 48-weeks
Inflammation and structural damages, including bone marrow edema, fatty deposition, erosions, syndesmophytes and ankylosis, in the spine and SIJs will be graded in MR images by certified radiologists using validated scoring systems developed by the Spondyloarthritis Research Consortium of Canada (SPARCC).
Measured: Change from Baseline at 48-weeks
Secondary outcomes (2)
Change in C-reactive protein (CRP) (in mg/dL) from Baseline at 48-weeks
CRP will be measured for evaluating inflammation activity.
Measured: Change from Baseline at 48-weeks
Change in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP at Baseline, 4-weeks, 48-weeks
The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess disease activity in Ankylosing Spondylitis (AS). It combines five disease activity variables with only partial overlap, resulting in one single score with better truth (validity), enhanced discriminative capacity and improved sensitivity to change as compared to single-item variables. ASDAS-CRP will be calculated as 0.12 x Back Pain + 0.06 x Duration of Morning Stiffness + 0.11 x Patient Global + 0.07 x Peripheral Pain/Swelling + 0.58 x Ln(CRP+1).
Measured: Change from Baseline at 48-weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start15 Jan 2020
- Primary completion31 Jul 2021
- Study completion31 Jul 2021
Why it stopped: Lack of enrollment due to the pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spondylitis, AnkylosingStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Francisco, UCB PHARMA Inc. (US)
- Responsible party
- Principal investigator, Xiaojuan Li, The Cleveland Clinic
- Investigators
- Xiaojuan Li, PhD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03778515
- Sponsor's protocol ID
- 18-1327
- Status last verified
- Aug 2022
- First submitted
- 27 Nov 2018
- Last updated
- 31 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Quantitative MRI for Axial Spondyloarthritis
- ClinicalTrials.gov ID
- NCT03778515
- Acronym / sponsor ID
- 18-1327
- Conditions
- Spondylitis, Ankylosing
- Keywords
- Axial, Spondyloarthritis, MRI, Ankylosing Spondylitis
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Lack of enrollment due to the pandemic
- Enrolment
- 1 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- University of California, San Francisco, UCB PHARMA Inc. (US)
- Study start
- 15 Jan 2020 (actual)
- Primary completion
- 31 Jul 2021 (actual)
- Study completion
- 31 Jul 2021 (actual)
- First posted
- 19 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This proposal aims to develop novel MR imaging and image processing techniques that will provide reliable and fully quantitative evaluation of inflammation, chronic structural changes and vascularity in patients with Ankylosing Spondylitis (AS). The quantitative evaluation will be more objective and reproducible, more sensitive to subtle changes, and less time consuming, as compared to the current semi-quantitative evaluation. It will allow radiologists and rheumatologists to evaluate the inflammation and structural changes more reliably to improve early diagnosis and treatment response evaluation. The developed quantification tools can be disseminated to other research and clinical sites for retrospective and prospective data analysis, and used as outcome measures for future multi-center trials. The evaluation of vascularity will enhance Investigators understanding of disease pathophysiology and serve as a novel marker to improve investigators capability of evaluating and predicting treatment response in AS. The successful implementation will greatly assist clinicians to optimize individualized therapeutic strategies and ultimately improve patient care for AS.
Detailed description
There is a critical and unmet clinical need for non-invasive techniques that provide early diagnosis as well as reliable and sensitive evaluations of ongoing disease activity and treatment response in patients with axial spondyloarthritis (axSpA). Imaging plays a key role to fulfill this goal and there is an increasing trend of applying imaging techniques in the field of axSpA. However, current imaging techniques, including radiographs and MRI, are primarily limited to qualitative or semi-quantitative evaluations of disease activity and structural damage, which is very crude and subjective with considerable inter-reader variation, and has limited sensitivity of detecting early lesions as well as changes in inflammatory lesions beyond morphology of bone marrow edema after treatment. Furthermore, several recent studies reported data of inflammation (bone marrow edema), fatty deposition and new bone formation after TNF inhibitor (TNFi) treatment in patients with axSpA, suggesting a complex relationship between inflammation, bone formation, and suppression of the TNF pathway. These studies also call for differentiating edema for their characteristics (angiogenesis for example) and inflammation stages (acute and chronic), which will provide valuable insight on disease pathophysiology as well as on optimizing treatment for individual patients with axSpA.
The long-term goal is to develop novel quantitative MRI measures that will reliably assess both inflammation and structural damage, and predict treatment response, remission and disease progression in axSpA. Compared to current MRI grading systems, such quantitative measures may be used as more sensitive, specific, reliable and faster imaging markers for future trials, and eventually for clinical practice to improve patient management in axSpA. In this proposal, Investigators will focus on patients with clinically diagnosed active Ankylosing Spondylitis (AS) and will develop novel imaging and image processing techniques using 3 Tesla MRI. The specific aims are two-folds. Firstly, Investigators will develop methods that reliably quantify bone marrow edema (BME), fatty deposition (FD) and erosions; Secondly, Investigators will develop novel quantitative evaluation of perfusion and vascularity of BME (using dynamic Gd-enhanced MRI), which has not been investigated for axSpA in the literature.
Investigators will recruit 20 patients with active Ankylosing Spondylitis (AS) using the 1984 modified NY criteria. Fifteen patients will be recruited from the Ankylosing Spondylitis clinic at UCSF, directed by Dr. Lianne Gensler, and five patients will be recruited from Rheumatology clinic at the Cleveland Clinic by Dr. Elaine Husni. Drs. Gensler and Husni will also reach out to the other academic sites and the community private practices to recruit patients as needed who are starting TNF inhibitor therapy with CZP for their AS. Patients will be studied at baseline, 4-weeks and 48-weeks after initiation of TNFi treatment. Advanced quantitative MRI will be applied to evaluate early treatment response at 4-weeks, and long-term outcomes at 48-weeks. The central hypothesis is that quantitative MRI allows a fast, specific and reproducible evaluation of disease activity and structural changes in AS, and provides more superior diagnostic and prognostic capability compared to semi-quantitative MRI grading systems.
The successful implementation of the proposed study will make significant contributions to the research and clinical
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases - Ankylosing Spondylitis Cohort | – | Diagnostic Test: MRI20 patients with ankylosing spondylitis (AS). Fifteen of these patients will be recruited from the Ankylosing Spondylitis clinic at the University of California, San Francisco. Five patients will be recruited from the Rheumatology clinic at the Cleveland Clinic. Observational with MRI. |
| Controls - w/o Ankylosing Spondylitis | – | Diagnostic Test: MRI5 patients without AS and with no history of any arthritis or lower back pain in this study. These 5 patients will make up the control group of the study, which means that they will provide a benchmark of comparison for the results investigators obtain from the active AS group. 2 of these 5 patients will be recruited from Cleveland Clinic, and 3 will be recruited from UCSF. Observational with MRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 15 patients will be recruited from the Ankylosing Spondylitis clinic at UCSF, and five patients will be recruited from Rheumatology clinic at the Cleveland Clinic. 10 patients with disease duration <= 10 years, and ten patients with disease duration > 10 years but without complete ankylosis. 5 healthy controls will be recruited for evaluating the measurement, with 2 from CCF and 3 from UCSF. The volunteers will be studied at baseline and 1-year follow up.
Key inclusion criteria (5 listed)
- Active AS meeting the modified New York criteria
- BASDAI ≥ 4
- Elevated C-Reactive Protein
- ≥ 18 years old
- Initiation of TNFi treatment with CZP
Key exclusion criteria (6 listed)
- Previous treatment with more than one biologics
- Biologic treatment within six-months (no more than 20% of group (n=4) for patients with previous biologic treatment)
- Non-response to previous anti TNF treatment
- Fibromyalgia or other reasons for back pain
- Pregnant patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIObservational Study of novel MR imaging and image processing techniques that will provide reliable and fully quantitative evaluation of inflammation, chronic structural changes and vascularity in patients with Ankylosing Spondylitis (AS). | Diagnostic test | Cases - Ankylosing Spondylitis Cohort, Controls - w/o Ankylosing Spondylitis |
Primary outcome
Change in Volume of MRI bone marrow edema (in cm^3) from Baseline at 48-weeks
Time frame: Change from Baseline at 48-weeks
Fully quantitative evaluation of volume of bone marrow edema (in cm^3) will be developed and applied in the study. Volume of BME will be calculated in both SIJ and Spine in high-resolution MR images to evaluate the active inflammation in the patients.
Change in MRI grading SPARCC from Baseline at 48-weeks
Time frame: Change from Baseline at 48-weeks
Inflammation and structural damages, including bone marrow edema, fatty deposition, erosions, syndesmophytes and ankylosis, in the spine and SIJs will be graded in MR images by certified radiologists using validated scoring systems developed by the Spondyloarthritis Research Consortium of Canada (SPARCC).
2 secondary outcomes
Change in C-reactive protein (CRP) (in mg/dL) from Baseline at 48-weeks
Time frame: Change from Baseline at 48-weeks
Change in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP at Baseline, 4-weeks, 48-weeks
Time frame: Change from Baseline at 48-weeks
Results and safety
The study was stopped early (reason given: Lack of enrollment due to the pandemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaojuan Li, PhD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spondylitis, Ankylosing, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Lack of enrollment due to the pandemic). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Volume of MRI bone marrow edema (in cm^3) from Baseline at 48-weeks (time frame: Change from Baseline at 48-weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2022.