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

Primary Sclerosing Cholangitis Clinical Trial

— CATCH-IT  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05462093
• Other study ID #: CATCH-IT
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2022
• Est. completion date: July 2029

Study information

• Verified date: July 2022
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Tim E Middelburg, MSC
• Phone: +31648510414
• Email: t.e.middelburg[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: July 2029
• Est. primary completion date: July 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Device:
• Liver Multiscan sequences
Additional Liver Multiscan sequences will be performed after the MRI liver with MRCP is performed, taking approximately 15 minutes.
• Liver Multiscan analysis
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.
• MRCP+
Post processing tool (Software) for quantifying MRCP images after the MRCP from follow up is performed. Patient involvement is not necessary during this procedure.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Perspectum

References & Publications (29)

Bachtiar V, Kelly MD, Wilman HR, Jacobs J, Newbould R, Kelly CJ, Gyngell ML, Groves KE, McKay A, Herlihy AH, Fernandes CC, Halberstadt M, Maguire M, Jayaratne N, Linden S, Neubauer S, Banerjee R. Repeatability and reproducibility of multiparametric magnetic resonance imaging of the liver. PLoS One. 2019 Apr 10;14(4):e0214921. doi: 10.1371/journal.pone.0214921. eCollection 2019. — View Citation

Banerjee R, Pavlides M, Tunnicliffe EM, Piechnik SK, Sarania N, Philips R, Collier JD, Booth JC, Schneider JE, Wang LM, Delaney DW, Fleming KA, Robson MD, Barnes E, Neubauer S. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014 Jan;60(1):69-77. doi: 10.1016/j.jhep.2013.09.002. Epub 2013 Sep 12. — View Citation

Barner-Rasmussen N, Pukkala E, Jussila A, Färkkilä M. Epidemiology, risk of malignancy and patient survival in primary sclerosing cholangitis: a population-based study in Finland. Scand J Gastroenterol. 2020 Jan;55(1):74-81. doi: 10.1080/00365521.2019.1707277. Epub 2020 Jan 4. — View Citation

Berstad AE, Aabakken L, Smith HJ, Aasen S, Boberg KM, Schrumpf E. Diagnostic accuracy of magnetic resonance and endoscopic retrograde cholangiography in primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2006 Apr;4(4):514-20. — View Citation

Boonstra K, Weersma RK, van Erpecum KJ, Rauws EA, Spanier BW, Poen AC, van Nieuwkerk KM, Drenth JP, Witteman BJ, Tuynman HA, Naber AH, Kingma PJ, van Buuren HR, van Hoek B, Vleggaar FP, van Geloven N, Beuers U, Ponsioen CY; EpiPSCPBC Study Group. Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis. Hepatology. 2013 Dec;58(6):2045-55. doi: 10.1002/hep.26565. Epub 2013 Oct 17. — View Citation

Bradley CR, Cox EF, Scott RA, James MW, Kaye P, Aithal GP, Francis ST, Guha IN. Multi-organ assessment of compensated cirrhosis patients using quantitative magnetic resonance imaging. J Hepatol. 2018 Nov;69(5):1015-1024. doi: 10.1016/j.jhep.2018.05.037. Epub 2018 Jun 8. — View Citation

Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, Gores GJ; American Association for the Study of Liver Diseases. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010 Feb;51(2):660-78. doi: 10.1002/hep.23294. — View Citation

Dave M, Elmunzer BJ, Dwamena BA, Higgins PD. Primary sclerosing cholangitis: meta-analysis of diagnostic performance of MR cholangiopancreatography. Radiology. 2010 Aug;256(2):387-96. doi: 10.1148/radiol.10091953. — View Citation

Eaton JE, Talwalkar JA, Lazaridis KN, Gores GJ, Lindor KD. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology. 2013 Sep;145(3):521-36. doi: 10.1053/j.gastro.2013.06.052. Epub 2013 Jul 1. Review. — View Citation

European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. Epub 2009 Jun 6. — View Citation

Goldfinger MH, Ridgway GR, Ferreira C, Langford CR, Cheng L, Kazimianec A, Borghetto A, Wright TG, Woodward G, Hassanali N, Nicholls RC, Simpson H, Waddell T, Vikal S, Mavar M, Rymell S, Wigley I, Jacobs J, Kelly M, Banerjee R, Brady JM. Quantitative MRCP Imaging: Accuracy, Repeatability, Reproducibility, and Cohort-Derived Normative Ranges. J Magn Reson Imaging. 2020 Sep;52(3):807-820. doi: 10.1002/jmri.27113. Epub 2020 Mar 8. — View Citation

Hirschfield GM, Karlsen TH, Lindor KD, Adams DH. Primary sclerosing cholangitis. Lancet. 2013 Nov 9;382(9904):1587-99. doi: 10.1016/S0140-6736(13)60096-3. Epub 2013 Jun 28. Review. — View Citation

Lazaridis KN, LaRusso NF. Primary Sclerosing Cholangitis. N Engl J Med. 2016 Sep 22;375(12):1161-70. doi: 10.1056/NEJMra1506330. Review. — View Citation

Lindor KD, Kowdley KV, Harrison ME; American College of Gastroenterology. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol. 2015 May;110(5):646-59; quiz 660. doi: 10.1038/ajg.2015.112. Epub 2015 Apr 14. — View Citation

Lunder AK, Hov JR, Borthne A, Gleditsch J, Johannesen G, Tveit K, Viktil E, Henriksen M, Hovde Ø, Huppertz-Hauss G, Høie O, Høivik ML, Monstad I, Solberg IC, Jahnsen J, Karlsen TH, Moum B, Vatn M, Negård A. Prevalence of Sclerosing Cholangitis Detected by Magnetic Resonance Cholangiography in Patients With Long-term Inflammatory Bowel Disease. Gastroenterology. 2016 Oct;151(4):660-669.e4. doi: 10.1053/j.gastro.2016.06.021. Epub 2016 Jun 21. — View Citation

Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018 Jun;27(6):1785-1805. doi: 10.1177/0962280216669183. Epub 2016 Sep 27. — View Citation

McDonald N, Eddowes PJ, Hodson J, Semple SIK, Davies NP, Kelly CJ, Kin S, Phillips M, Herlihy AH, Kendall TJ, Brown RM, Neil DAH, Hübscher SG, Hirschfield GM, Fallowfield JA. Multiparametric magnetic resonance imaging for quantitation of liver disease: a two-centre cross-sectional observational study. Sci Rep. 2018 Jun 15;8(1):9189. doi: 10.1038/s41598-018-27560-5. — View Citation

Okada F, Izutsu R, Goto K, Osaki M. Inflammation-Related Carcinogenesis: Lessons from Animal Models to Clinical Aspects. Cancers (Basel). 2021 Feb 22;13(4). pii: 921. doi: 10.3390/cancers13040921. Review. — View Citation

Pavlides M, Banerjee R, Sellwood J, Kelly CJ, Robson MD, Booth JC, Collier J, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb;64(2):308-315. doi: 10.1016/j.jhep.2015.10.009. Epub 2015 Nov 10. — View Citation

Pavlides M, Banerjee R, Tunnicliffe EM, Kelly C, Collier J, Wang LM, Fleming KA, Cobbold JF, Robson MD, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity. Liver Int. 2017 Jul;37(7):1065-1073. doi: 10.1111/liv.13284. Epub 2017 May 30. — View Citation

Ponsioen CY, Assis DN, Boberg KM, Bowlus CL, Deneau M, Thorburn D, Aabakken L, Färkkilä M, Petersen B, Rupp C, Hübscher SG; PSC Study Group. Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process. Gastroenterology. 2021 Dec;161(6):1764-1775.e5. doi: 10.1053/j.gastro.2021.07.046. Epub 2021 Aug 10. — View Citation

Ponsioen CY, Chapman RW, Chazouillères O, Hirschfield GM, Karlsen TH, Lohse AW, Pinzani M, Schrumpf E, Trauner M, Gores GJ. Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process. Hepatology. 2016 Apr;63(4):1357-67. doi: 10.1002/hep.28256. Epub 2015 Dec 23. Review. — View Citation

Ponsioen CY, Reitsma JB, Boberg KM, Aabakken L, Rauws EA, Schrumpf E. Validation of a cholangiographic prognostic model in primary sclerosing cholangitis. Endoscopy. 2010 Sep;42(9):742-7. doi: 10.1055/s-0030-1255527. Epub 2010 Jul 9. — View Citation

Schramm C, Eaton J, Ringe KI, Venkatesh S, Yamamura J; MRI working group of the IPSCSG. Recommendations on the use of magnetic resonance imaging in PSC-A position statement from the International PSC Study Group. Hepatology. 2017 Nov;66(5):1675-1688. doi: 10.1002/hep.29293. Epub 2017 Sep 29. Review. — View Citation

Selvaraj EA, Culver EL, Collier J, Ridgway GR, Brady JM, Bailey A, et al. Combination of quantitative MRCP and MRI demonstrates increased periductal iron-corrected T1 in primary sclerosing cholangitis. Gut. 2021;70(Suppl 1):A155.

Tunnicliffe EM, Banerjee R, Pavlides M, Neubauer S, Robson MD. A model for hepatic fibrosis: the competing effects of cell loss and iron on shortened modified Look-Locker inversion recovery T(1) (shMOLLI-T(1) ) in the liver. J Magn Reson Imaging. 2017 Feb;45(2):450-462. doi: 10.1002/jmri.25392. Epub 2016 Jul 23. — View Citation

Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014 Dec 19;14:135. doi: 10.1186/1471-2288-14-135. — View Citation

Zenouzi R, Welle CL, Venkatesh SK, Schramm C, Eaton JE. Magnetic Resonance Imaging in Primary Sclerosing Cholangitis-Current State and Future Directions. Semin Liver Dis. 2019 Jul;39(3):369-380. doi: 10.1055/s-0039-1687853. Epub 2019 Apr 30. Review. — View Citation

Zheng HH, Jiang XL. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies. Eur J Gastroenterol Hepatol. 2016 Apr;28(4):383-90. doi: 10.1097/MEG.0000000000000576. Review. — View Citation

* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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;
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.