Dose Effect Relationship of MTX and IBD
Dose Effect Relationship of Methotrexate and Hepatic Fibrosis in Patients With Inflammatory Bowel Disease
1 other identifier
observational
64
1 country
1
Brief Summary
Currently there are no guidelines for monitoring hepatic fibrosis associated with long term MTX use. Routine liver biopsies are not being done as a part of surveillance due to potential complications like bleeding and pneumothorax. Non-invasive markers like gammaglamyltransferase (GGTP), Alkaline Phosphatase (AlkPhos), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are deranged at a late stage and may not be helpful in detecting early fibrosis. The current study will utilize a sensitive, but noninvasive, test to evaluate for hepatic fibrosis. We are attempting to screen for early detection of fibrosis due to MTX before it progresses to irreversible cirrhosis and end-stage liver disease. Based on the results of this pilot study, ultrasound elastography could be used to prospectively study a larger population to establish guidelines for monitoring safety and hepatic complications with MTX. The influence of other co-morbid factors like obesity, alcohol ingestion and smoking is critical to identifying high risk patients who may require closer monitoring. We follow close to 550 patients with IBD. If we presume that at least 20% patients are currently receiving methotrexate, we will be able to recruit enough patients for this pilot study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Feb 2017
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2017
CompletedFirst Submitted
Initial submission to the registry
April 26, 2017
CompletedFirst Posted
Study publicly available on registry
May 22, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 31, 2018
CompletedJuly 17, 2018
July 1, 2018
1.3 years
April 26, 2017
July 16, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Primary Objective - correlation between velocities of shear wave elastography and cumulative dose of Methotrexate (MTX) in patients with Inflammatory Bowel Disease (IBD).
To evaluate the correlation between velocities of shear wave elastography and cumulative dose of Methotrexate (MTX) in patients with Inflammatory Bowel Disease (IBD).
2/1/2017-10/31/2017
Secondary Outcomes (3)
Secondary Objective - correlate hepatic enzymes elevation and ultrasound elastography velocities
2/1/2017-10/31/2017
Third Objective - changes in shear wave velocity
2/1/2017-10/31/2017
Fourth Objective - correlate ultrasound elastography findings with fibrosis markers
2/1/2017-10/31/2017
Study Arms (1)
US Elastography
All subjects will undergo one ultrasound elastography examination after consent.
Interventions
Ultrasound elastography is a new, noninvasive technique that can assess the stiffness of the liver by the evaluation of how sound waves propagate through the liver parenchyma.
Eligibility Criteria
Patients ages 2-22 whom have a diagnosis of IBD can participate in our study. We will recruit a total of 100 subjects; 25 control subjects and 75 subjects whom are taking Methotrexate for their IBD.
You may qualify if:
- Patients age 2-22 years of age who have a diagnosis of IBD and consent to our study.
You may not qualify if:
- Patient is unable to tolerate an ultrasound elastography examination.
- Target enrollment for the MTX dose category in which the patient fits has been completed.
- Any preexisting liver disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Related Publications (9)
Asrani SK. Incorporation of Noninvasive Measures of Liver Fibrosis Into Clinical Practice: Diagnosis and Prognosis. Clin Gastroenterol Hepatol. 2015 Nov;13(12):2190-204. doi: 10.1016/j.cgh.2015.07.030. Epub 2015 Jul 27.
PMID: 26226095RESULTBarbero-Villares A, Mendoza Jimenez-Ridruejo J, Taxonera C, Lopez-Sanroman A, Pajares R, Bermejo F, Perez-Calle JL, Mendoza JL, Algaba A, Moreno-Otero R, Mate J, Gisbert JP; Madrid Group for the Study of Inflammatory Bowel Disease ENICMAD. Evaluation of liver fibrosis by transient elastography (Fibroscan(R)) in patients with inflammatory bowel disease treated with methotrexate: a multicentric trial. Scand J Gastroenterol. 2012 May;47(5):575-9. doi: 10.3109/00365521.2011.647412. Epub 2012 Jan 10.
PMID: 22229701RESULTBota S, Paternostro R, Etschmaier A, Schwarzer R, Salzl P, Mandorfer M, Kienbacher C, Ferlitsch M, Reiberger T, Trauner M, Peck-Radosavljevic M, Ferlitsch A. Performance of 2-D shear wave elastography in liver fibrosis assessment compared with serologic tests and transient elastography in clinical routine. Ultrasound Med Biol. 2015 Sep;41(9):2340-9. doi: 10.1016/j.ultrasmedbio.2015.04.013. Epub 2015 May 23.
PMID: 26004669RESULTKhan N, Abbas AM, Whang N, Balart LA, Bazzano LA, Kelly TN. Incidence of liver toxicity in inflammatory bowel disease patients treated with methotrexate: a meta-analysis of clinical trials. Inflamm Bowel Dis. 2012 Feb;18(2):359-67. doi: 10.1002/ibd.21820. Epub 2011 Jul 12.
PMID: 21751301RESULTTe HS, Schiano TD, Kuan SF, Hanauer SB, Conjeevaram HS, Baker AL. Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease. Am J Gastroenterol. 2000 Nov;95(11):3150-6. doi: 10.1111/j.1572-0241.2000.03287.x.
PMID: 11095334RESULTValentino PL, Church PC, Shah PS, Beyene J, Griffiths AM, Feldman BM, Kamath BM. Hepatotoxicity caused by methotrexate therapy in children with inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2014 Jan;20(1):47-59. doi: 10.1097/01.MIB.0000436953.88522.3e.
PMID: 24280876RESULTDillman JR, Heider A, Bilhartz JL, Smith EA, Keshavarzi N, Rubin JM, Lopez MJ. Ultrasound shear wave speed measurements correlate with liver fibrosis in children. Pediatr Radiol. 2015 Sep;45(10):1480-8. doi: 10.1007/s00247-015-3345-5. Epub 2015 Apr 8.
PMID: 25851300RESULTKim TY, Kim JY, Sohn JH, Lee HS, Bang SY, Kim Y, Kim MY, Jeong WK. Assessment of Substantial Liver Fibrosis by Real-time Shear Wave Elastography in Methotrexate-Treated Patients With Rheumatoid Arthritis. J Ultrasound Med. 2015 Sep;34(9):1621-30. doi: 10.7863/ultra.15.14.10035. Epub 2015 Aug 12.
PMID: 26269292RESULTMalatjalian DA, Ross JB, Williams CN, Colwell SJ, Eastwood BJ. Methotrexate hepatotoxicity in psoriatics: report of 104 patients from Nova Scotia, with analysis of risks from obesity, diabetes and alcohol consumption during long term follow-up. Can J Gastroenterol. 1996 Oct;10(6):369-75. doi: 10.1155/1996/213596.
PMID: 9193771RESULT
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 26, 2017
First Posted
May 22, 2018
Study Start
February 1, 2017
Primary Completion
May 31, 2018
Study Completion
May 31, 2018
Last Updated
July 17, 2018
Record last verified: 2018-07
Data Sharing
- IPD Sharing
- Will not share