Clinical Application of Annual Liver Multiscan and MRCP+ in Primary Sclerosing Cholangitis

Study Overview
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Brief Summary
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Primary sclerosing cholangitis (PSC) is a chronic progressive biliary disease that affects approximately 1200 patients in the Netherlands and around 80,000 in the Western world. It is often accompanied by ulcerative colitis (UC) or Crohn's disease affecting the large bowel. The cause of PSC is unknown, there is no medical therapy available that has proven to halt disease progression and the median time until death or liver transplantation is 13-21 years. Diagnosis is made by magnetic resonance cholangiography (MRC), or in the case of so called small duct disease by liver biopsy. Due to the heterogeneous disease course and the relatively low clinical event rate of 5% per year it is difficult to predict prognosis of individual patients or to recommend any surveillance strategy for malignancies. Also, the lack of surrogate endpoints impedes performing clinical research. Recently, two new post-processing tools have been developed to characterize and quantify abnormalities in the biliary tree as well as excretory function captured by MRC. These tools called MRCP+ (quantitative magnetic resonance cholangiopancreatography +) and LiverMultiscan (LMS) hold the prospect of adequately depicting and quantifying lesions of the biliary tree as well as capturing functional derailment. However, several features must be tested before the utility of this tools in clinical patient care can be concluded. Therefore, the aim of this study is to investigate the utility of these novel techniques in monitoring disease activity by performing consecutive annual MRI's.

Official Title
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Clinical Application of Annual Liver Multiscan and MRCP+ in Primary Sclerosing Cholangitis: the CATCH-IT Study

Conditions
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Primary Sclerosing Cholangitis

Intervention / Treatment
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* Device: Liver Multiscan sequences
* Device: Liver Multiscan analysis
* Device: MRCP+


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established PSC diagnosis according to the IPSCSG definitions Age ≥ 18 Able to give informed consent Exclusion Criteria: Post LTx Known allergy for MRI contrast agents, implants non-compatible with MRI or extreme claustrophobia causing discontinuation of MRI studies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Additional sequences with MRCP+ and LiverMultiscan<br>PSC patients that undergo annual, standard care, MRI of the liver and MRCP will undergo additional Liver Multiscan sequences, taking approximately 15 minutes. After the MRI is performed, post-processing analysis named MRCP+ and LiverMultiscan will be performed without patient involvement. | Device: Liver Multiscan sequences<br>* Additional Liver Multiscan sequences will be performed after the MRI liver with MRCP is performed, taking approximately 15 minutes.<br>Device: Liver Multiscan analysis<br>* Post processing tool (Software) for determining the corrected T1 time after the additional LMS sequences at baseline are performed. This cT1 reflects the activity of inflammation/fibrosis of the liver. Patient involvement is not necessary during this procedure.<br>* Other names: LMS;Device: MRCP+<br>* Post processing tool (Software) for quantifying MRCP images after the MRCP from follow up is performed. Patient involvement is not necessary during this procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta of cT1 in patients with PSC during follow-up | The delta of cT1 (in ms), measured by LiverMultiscan, which will be assessed by performing paired t-tests. | 1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assesment of th mean, median and range of cT1 and MRCP+ metrics in stable PSC patients | Mean, median and range of cT1 and MRCP+ metrics in clinically and biochemically stable patients with PSC during the period of 1 year to establish general statistics as these are unknown at current writing | 1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; | 
| Variance of the delta of cT1 and MRCP+ metrics in stable patients | Variance of the delta in cT1 and MRCP+ metrics from baseline to year 1 in clinically and biochemically stable patients | 1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260. | 
| Difference in cT1 in patients with or without endoscopic intervention | Difference in mean of cT1 values in patients who needed ERCP with treatment of dominant stricture(s) in the year following LMS measurement versus those who did not need an intervention | 1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260. | 
| Variance in unstable patients | Variance of the delta of cT1 and MRCP+ metrics in sequential scans in biochemically and/or clinically deteriorating patients. | 1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260. | 
| Correlation of cT1 and MRCP+ metrics with fibroscan and MELD | Correlation between cT1 and MRCP+ metrics with Fibroscan and MELD-score | 1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260. | 
| Correlation of cT1 and MRCP+ metrics and development of dominant strictures | Correlation between cT1 and MRCP+ metrics and development of dominant strictures | 1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260. | 
| Correlation of cT1 and MRCP+ metrics and incidence of CCA | Correlation between cT1 and MRCP+ metrics and incidence of CCA | 1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260. |