Back to results

Development of an Imaging Biomarker for Hepatic Fibrosis Using Gadoxetate Disodium

Primary Purpose

Hepatic Fibrosis

Status

Unknown status

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

MRI of liver

About this trial

This is an interventional diagnostic trial for Hepatic Fibrosis focused on measuring hepatic fibrosis, Eovist, gadoxetate disodium, biomarker, liver biopsy, liver function, MRI, Hepatitis C

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria:

subjects with Hepatitis C who are scheduled to obtain a liver biopsy in the future or have obtained a liver biopsy in the 6 months prior to planned MR imaging or
subjects who are healthy, without liver disease (used for normal controls)

All subpopulations regarding gender, race and ethnicity will have equal opportunity for inclusion in the study protocol. The study protocol only includes adult population consistent with the age (>21 years old) at presentation.

Exclusion criteria:

subjects with any contraindication to obtaining an MRI with intravenous contrast including: metal in body, severe renal impairment, pregnancy, or breast feeding. Contraindications will be identified using the same screening questionnaire as is provided for routine clinical examinations.
Subjects with history of allergy to MRI contrast dye

Severe renal impairment is defined as a glomerular filtration rate (GFR) < 30 mL/min/1.73 m2. All subjects will be screened with a questionnaire. The GFR will be calculated in any subject who reports kidney problems or a history of kidney problems using blood chemistries performed within 6 weeks of the planned date of the MRI examination. These blood chemistries would need to have been performed as part of routine clinical care. A potential subject who reports kidney problems or a history of kidney problems who does not have blood chemistries available within 6 weeks of the MRI examination will be excluded from participation in this study.

Sites / Locations

Weill Cornell Medical CollegeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Normal liver function

Hepatitis C

Arm Description

Control group. Subjects will obtain MRI of liver.

Subjects with hepatitis C. Subjects will obtain both MRI of liver and limited CT of liver.

Outcomes

Primary Outcome Measures

The transfer constant, Ktrans, between intravascular and interstitial compartments.

Ktrans is a transfer constant obtained following analysis of all images in the MRI exam, and is a measure of the permeability of tissue.

Secondary Outcome Measures

Full Information

NCT ID

NCT01783314

First Posted

November 18, 2011

Last Updated

January 31, 2013

Sponsor

Weill Medical College of Cornell University

1. Study Identification

Unique Protocol Identification Number

NCT01783314

Brief Title

Development of an Imaging Biomarker for Hepatic Fibrosis Using Gadoxetate Disodium

Official Title

Development of an Imaging Biomarker for Hepatic Fibrosis Using Gadoxetate Disodium

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Unknown status

Study Start Date

December 2010 (undefined)

Primary Completion Date

December 2013 (Anticipated)

Study Completion Date

December 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Weill Medical College of Cornell University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

When someone has hepatitis C or some other condition that causes liver injury, he or she can develop a condition called liver fibrosis that over time, can cause the liver to stop working normally. Currently, the best way to determine the degree of fibrosis is to do a liver biopsy. The investigators hope to show that measuring the degree of liver fibrosis using an MRI with gadoxetate disodium is as good as or better than obtaining this information by performing a liver biopsy. Gadoxetate disodium is a contrast solution given through the veins that is considered safe, is approved for use by the Food and Drug Administration, and is already routinely given to patients with various forms of liver disease, including fibrosis.

Detailed Description

Liver damage, from a variety of causes, leads to a condition called liver fibrosis. Common causes are chronic alcohol use and hepatitis C infection. The condition can progress to cirrhosis and liver failure, and is the seventh leading cause of death in the United States. Presently, biopsy remains the only reliable way to test whether the various treatments that have been proposed are working, but the risks of biopsy preclude frequent re-assessment. Hence, truly personalized treatments are hampered by the lack of a non-invasive, low-risk, but appropriately qualified test by which periodic assessments may be made. In July of 2008, the FDA approved a new drug called Eovist that is absorbed by liver cells and can be seen in the liver when performing an MRI. The amount and time course of Eovist absorption will be different between health and fibrotic liver tissue. We believe that these parameters, in combination with hematological and immunological blood tests, can predict the degree of liver fibrosis without the need for biopsy. This would allow improved assessment of potentially important interventions that might alter the course of the underlying disease. Thus development of this non-invasive biomarker might not only obviate the need for biopsy, but might in addition allow more intensive periodic assessments that are not possible currently.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatic Fibrosis

Keywords

hepatic fibrosis, Eovist, gadoxetate disodium, biomarker, liver biopsy, liver function, MRI, Hepatitis C

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Normal liver function

Arm Type

Active Comparator

Arm Description

Control group. Subjects will obtain MRI of liver.

Arm Title

Hepatitis C

Arm Type

Experimental

Arm Description

Subjects with hepatitis C. Subjects will obtain both MRI of liver and limited CT of liver.

Intervention Type

Procedure

Intervention Name(s)

MRI of liver

Intervention Description

MRI of liver with intravenous gadoxetate disodium

Primary Outcome Measure Information:

Title

The transfer constant, Ktrans, between intravascular and interstitial compartments.

Description

Ktrans is a transfer constant obtained following analysis of all images in the MRI exam, and is a measure of the permeability of tissue.

Time Frame

up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: subjects with Hepatitis C who are scheduled to obtain a liver biopsy in the future or have obtained a liver biopsy in the 6 months prior to planned MR imaging or subjects who are healthy, without liver disease (used for normal controls) All subpopulations regarding gender, race and ethnicity will have equal opportunity for inclusion in the study protocol. The study protocol only includes adult population consistent with the age (>21 years old) at presentation. Exclusion criteria: subjects with any contraindication to obtaining an MRI with intravenous contrast including: metal in body, severe renal impairment, pregnancy, or breast feeding. Contraindications will be identified using the same screening questionnaire as is provided for routine clinical examinations. Subjects with history of allergy to MRI contrast dye Severe renal impairment is defined as a glomerular filtration rate (GFR) < 30 mL/min/1.73 m2. All subjects will be screened with a questionnaire. The GFR will be calculated in any subject who reports kidney problems or a history of kidney problems using blood chemistries performed within 6 weeks of the planned date of the MRI examination. These blood chemistries would need to have been performed as part of routine clinical care. A potential subject who reports kidney problems or a history of kidney problems who does not have blood chemistries available within 6 weeks of the MRI examination will be excluded from participation in this study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ame Ng, BSN, CCRP

Phone

212-746-2194

ameng@med.cornell.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Krishna Juluru, MD

Organizational Affiliation

Weill Medical College of Cornell University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Weill Cornell Medical College

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ame Ng

Phone

212-746-2194

ameng@med.cornell.edu

First Name & Middle Initial & Last Name & Degree

Krishna Juluru, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

2869260

Citation

Maharaj B, Maharaj RJ, Leary WP, Cooppan RM, Naran AD, Pirie D, Pudifin DJ. Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver. Lancet. 1986 Mar 8;1(8480):523-5. doi: 10.1016/s0140-6736(86)90883-4.

Results Reference

background

PubMed Identifier

6217961

Citation

Pagliaro L, Rinaldi F, Craxi A, Di Piazza S, Filippazzo G, Gatto G, Genova G, Magrin S, Maringhini A, Orsini S, Palazzo U, Spinello M, Vinci M. Percutaneous blind biopsy versus laparoscopy with guided biopsy in diagnosis of cirrhosis. A prospective, randomized trial. Dig Dis Sci. 1983 Jan;28(1):39-43. doi: 10.1007/BF01393359.

Results Reference

background

PubMed Identifier

17351431

Citation

Tsuda N, Okada M, Murakami T. Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging. Invest Radiol. 2007 Apr;42(4):242-7. doi: 10.1097/01.rli.0000258058.44876.a5.

Results Reference

background

PubMed Identifier

19341415

Citation

Berg CL, Steffick DE, Edwards EB, Heimbach JK, Magee JC, Washburn WK, Mazariegos GV. Liver and intestine transplantation in the United States 1998-2007. Am J Transplant. 2009 Apr;9(4 Pt 2):907-31. doi: 10.1111/j.1600-6143.2009.02567.x.

Results Reference

background

PubMed Identifier

21879400

Citation

Chen BB, Hsu CY, Yu CW, Wei SY, Kao JH, Lee HS, Shih TT. Dynamic contrast-enhanced magnetic resonance imaging with Gd-EOB-DTPA for the evaluation of liver fibrosis in chronic hepatitis patients. Eur Radiol. 2012 Jan;22(1):171-80. doi: 10.1007/s00330-011-2249-5. Epub 2011 Aug 31.

Results Reference

background

PubMed Identifier

8537493

Citation

Olsson R, Hagerstrand I, Broome U, Danielsson A, Jarnerot G, Loof L, Prytz H, Ryden BO, Wallerstedt S. Sampling variability of percutaneous liver biopsy in primary sclerosing cholangitis. J Clin Pathol. 1995 Oct;48(10):933-5. doi: 10.1136/jcp.48.10.933.

Results Reference

background

PubMed Identifier

8781934

Citation

Poniachik J, Bernstein DE, Reddy KR, Jeffers LJ, Coelho-Little ME, Civantos F, Schiff ER. The role of laparoscopy in the diagnosis of cirrhosis. Gastrointest Endosc. 1996 Jun;43(6):568-71. doi: 10.1016/s0016-5107(96)70192-x.

Results Reference

background

PubMed Identifier

17885048

Citation

Taouli B, Tolia AJ, Losada M, Babb JS, Chan ES, Bannan MA, Tobias H. Diffusion-weighted MRI for quantification of liver fibrosis: preliminary experience. AJR Am J Roentgenol. 2007 Oct;189(4):799-806. doi: 10.2214/AJR.07.2086.

Results Reference

background

PubMed Identifier

14647056

Citation

Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003 Dec;38(6):1449-57. doi: 10.1016/j.hep.2003.09.022.

Results Reference

background

PubMed Identifier

12385448

Citation

Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, Feng ZZ, Reddy KR, Schiff ER. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002 Oct;97(10):2614-8. doi: 10.1111/j.1572-0241.2002.06038.x.

Results Reference

background

PubMed Identifier

11403201

Citation

Kovalev VA, Kruggel F, Gertz HJ, von Cramon DY. Three-dimensional texture analysis of MRI brain datasets. IEEE Trans Med Imaging. 2001 May;20(5):424-33. doi: 10.1109/42.925295.

Results Reference

background

PubMed Identifier

16118550

Citation

Segers J, Le Duc G, Laumonier C, Tropres I, Elst LV, Muller RN. Evaluation of Gd-EOB-DTPA uptake in a perfused and isolated mouse liver model: correlation between magnetic resonance imaging and monochromatic quantitative computed tomography. Invest Radiol. 2005 Sep;40(9):574-82. doi: 10.1097/01.rli.0000174474.43772.58.

Results Reference

background

PubMed Identifier

9243389

Citation

Kim T, Murakami T, Hasuike Y, Gotoh M, Kato N, Takahashi M, Miyazawa T, Narumi Y, Monden M, Nakamura H. Experimental hepatic dysfunction: evaluation by MRI with Gd-EOB-DTPA. J Magn Reson Imaging. 1997 Jul-Aug;7(4):683-8. doi: 10.1002/jmri.1880070413.

Results Reference

background

PubMed Identifier

18098299

Citation

Romero-Gomez M, Gomez-Gonzalez E, Madrazo A, Vera-Valencia M, Rodrigo L, Perez-Alvarez R, Perez-Lopez R, Castellano-Megias VM, Nevado-Santos M, Alcon JC, Sola R, Perez-Moreno JM, Navarro JM, Andrade RJ, Salmeron J, Fernandez-Lopez M, Aznar R, Diago M. Optical analysis of computed tomography images of the liver predicts fibrosis stage and distribution in chronic hepatitis C. Hepatology. 2008 Mar;47(3):810-6. doi: 10.1002/hep.22112.

Results Reference

background

PubMed Identifier

18666132

Citation

Asbach P, Klatt D, Hamhaber U, Braun J, Somasundaram R, Hamm B, Sack I. Assessment of liver viscoelasticity using multifrequency MR elastography. Magn Reson Med. 2008 Aug;60(2):373-9. doi: 10.1002/mrm.21636.

Results Reference

background

PubMed Identifier

16510096

Citation

Mendoza J, Gomez-Dominguez E, Moreno-Otero R. [Transient elastography (Fibroscan), a new non-invasive method to evaluate hepatic fibrosis]. Med Clin (Barc). 2006 Feb 18;126(6):220-2. doi: 10.1157/13084871. No abstract available. Spanish.

Results Reference

background

PubMed Identifier

17014063

Citation

Murtagh J, Foerster V. Transient elastography (FibroScan) for non-invasive assessment of liver fibrosis. Issues Emerg Health Technol. 2006 Sep;(90):1-4.

Results Reference

background

PubMed Identifier

15922482

Citation

Zeremski M, Talal AH. Noninvasive markers of hepatic fibrosis: are they ready for prime time in the management of HIV/HCV co-infected patients? J Hepatol. 2005 Jul;43(1):2-5. doi: 10.1016/j.jhep.2005.05.007. No abstract available.

Results Reference

background

PubMed Identifier

7754011

Citation

Hamm B, Staks T, Muhler A, Bollow M, Taupitz M, Frenzel T, Wolf KJ, Weinmann HJ, Lange L. Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. Radiology. 1995 Jun;195(3):785-92. doi: 10.1148/radiology.195.3.7754011.

Results Reference

background

PubMed Identifier

19026502

Citation

Tsuda N, Okada M, Murakami T. New proposal for the staging of nonalcoholic steatohepatitis: evaluation of liver fibrosis on Gd-EOB-DTPA-enhanced MRI. Eur J Radiol. 2010 Jan;73(1):137-42. doi: 10.1016/j.ejrad.2008.09.036. Epub 2008 Nov 20.

Results Reference

background

PubMed Identifier

17478617

Citation

Schuster DP. The opportunities and challenges of developing imaging biomarkers to study lung function and disease. Am J Respir Crit Care Med. 2007 Aug 1;176(3):224-30. doi: 10.1164/rccm.200703-462PP. Epub 2007 May 3.

Results Reference

background

PubMed Identifier

11385966

Citation

Albanis E, Friedman SL. Hepatic fibrosis. Pathogenesis and principles of therapy. Clin Liver Dis. 2001 May;5(2):315-34, v-vi. doi: 10.1016/s1089-3261(05)70168-9.

Results Reference

background

PubMed Identifier

10644669

Citation

Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 2000 Jan 28;275(4):2247-50. doi: 10.1074/jbc.275.4.2247. No abstract available.

Results Reference

background

PubMed Identifier

2061479

Citation

Brix G, Semmler W, Port R, Schad LR, Layer G, Lorenz WJ. Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J Comput Assist Tomogr. 1991 Jul-Aug;15(4):621-8. doi: 10.1097/00004728-199107000-00018.

Results Reference

background

PubMed Identifier

21775085

Citation

Motosugi U, Ichikawa T, Oguri M, Sano K, Sou H, Muhi A, Matsuda M, Fujii H, Enomoto N, Araki T. Staging liver fibrosis by using liver-enhancement ratio of gadoxetic acid-enhanced MR imaging: comparison with aspartate aminotransferase-to-platelet ratio index. Magn Reson Imaging. 2011 Oct;29(8):1047-52. doi: 10.1016/j.mri.2011.05.007. Epub 2011 Jul 19.

Results Reference

background

PubMed Identifier

16970596

Citation

Christensen C, Bruden D, Livingston S, Deubner H, Homan C, Smith K, Oh E, Gretch D, Williams J, McMahon B. Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with Knodell and Ishak liver biopsy scores in chronic hepatitis C patients. J Viral Hepat. 2006 Oct;13(10):652-8. doi: 10.1111/j.1365-2893.2006.00743.x.

Results Reference

background

PubMed Identifier

15637473

Citation

Ryeom HK, Kim SH, Kim JY, Kim HJ, Lee JM, Chang YM, Kim YS, Kang DS. Quantitative evaluation of liver function with MRI Using Gd-EOB-DTPA. Korean J Radiol. 2004 Oct-Dec;5(4):231-9. doi: 10.3348/kjr.2004.5.4.231.

Results Reference

background

PubMed Identifier

9561050

Citation

Murakami T, Kim T, Gotoh M, Hasuike Y, Kato N, Miyazawa T, Monden M, Nakamura H. Experimental hepatic dysfunction: evaluation by MR imaging with Gd-EOB-DTPA. Acad Radiol. 1998 Apr;5 Suppl 1:S80-2. doi: 10.1016/s1076-6332(98)80067-6. No abstract available.

Results Reference

background

PubMed Identifier

10489914

Citation

Shimizu J, Dono K, Gotoh M, Hasuike Y, Kim T, Murakami T, Sakon M, Umeshita K, Nagano H, Nakamori S, Kato N, Miyazawa T, Nakamura H, Monden M. Evaluation of regional liver function by gadolinium-EOB-DTPA-enhanced MR imaging. Dig Dis Sci. 1999 Jul;44(7):1330-7. doi: 10.1023/a:1026679113772.

Results Reference

background

PubMed Identifier

11933597

Citation

Ji H, Ros PR. Magnetic resonance imaging. Liver-specific contrast agents. Clin Liver Dis. 2002 Feb;6(1):73-90. doi: 10.1016/s1089-3261(03)00067-9.

Results Reference

background

PubMed Identifier

19215579

Citation

Moreno S, Garcia-Samaniego J, Moreno A, Ortega E, Pineda JA, del Romero J, Tural C, von Wichmann MA, Berenguer J, Castro A, Espacio R. Noninvasive diagnosis of liver fibrosis in patients with HIV infection and HCV/HBV co-infection. J Viral Hepat. 2009 Apr;16(4):249-58. doi: 10.1111/j.1365-2893.2009.01088.x. Epub 2009 Feb 7.

Results Reference

background

PubMed Identifier

16387510

Citation

Laking GR, West C, Buckley DL, Matthews J, Price PM. Imaging vascular physiology to monitor cancer treatment. Crit Rev Oncol Hematol. 2006 May;58(2):95-113. doi: 10.1016/j.critrevonc.2005.10.006. Epub 2006 Jan 4.

Results Reference

background

PubMed Identifier

18760935

Citation

Marcus CD, Ladam-Marcus V, Cucu C, Bouche O, Lucas L, Hoeffel C. Imaging techniques to evaluate the response to treatment in oncology: current standards and perspectives. Crit Rev Oncol Hematol. 2009 Dec;72(3):217-38. doi: 10.1016/j.critrevonc.2008.07.012. Epub 2008 Aug 29.

Results Reference

background

PubMed Identifier

16549620

Citation

d'Arcy JA, Collins DJ, Padhani AR, Walker-Samuel S, Suckling J, Leach MO. Informatics in Radiology (infoRAD): Magnetic Resonance Imaging Workbench: analysis and visualization of dynamic contrast-enhanced MR imaging data. Radiographics. 2006 Mar-Apr;26(2):621-32. doi: 10.1148/rg.262045187.

Results Reference

background

PubMed Identifier

18195377

Citation

Hagiwara M, Rusinek H, Lee VS, Losada M, Bannan MA, Krinsky GA, Taouli B. Advanced liver fibrosis: diagnosis with 3D whole-liver perfusion MR imaging--initial experience. Radiology. 2008 Mar;246(3):926-34. doi: 10.1148/radiol.2463070077. Epub 2008 Jan 14.

Results Reference

background

PubMed Identifier

16641352

Citation

Aguirre DA, Behling CA, Alpert E, Hassanein TI, Sirlin CB. Liver fibrosis: noninvasive diagnosis with double contrast material-enhanced MR imaging. Radiology. 2006 May;239(2):425-37. doi: 10.1148/radiol.2392050505.

Results Reference

background

Learn more about this trial

Development of an Imaging Biomarker for Hepatic Fibrosis Using Gadoxetate Disodium

We'll reach out to this number within 24 hrs