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Trial record 2 of 3 for:    XBP1 AND transplantation

Fatty Acids Lipidome and Oxidative Stress in Liver Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01389115
Recruitment Status : Unknown
Verified December 2015 by Luigi Iuliano, University of Roma La Sapienza.
Recruitment status was:  Recruiting
First Posted : July 7, 2011
Last Update Posted : December 11, 2015
Information provided by (Responsible Party):
Luigi Iuliano, University of Roma La Sapienza

Brief Summary:
The purpose of this study is to determine lipid metabolism in chronic liver disease in the attempt to find a useful biomarker of liver function and of prognostic value of graft function in those patients who undergo liver transplant. The present study enrolls subjects with liver cirrhosis (with different ethiology), including subjects eligible for a full-size liver transplantation, and healthy controls.

Condition or disease
Liver Cirrhosis

Detailed Description:
Liver has a central role in fatty acids metabolism that is impaired in chronic liver diseases. Polyunsaturated fatty acids are reportedly reduced in liver cirrhosis, which is considered a condition of essential fatty acids deficiency. However, there is a paucity of data concerning the level of the multitude of circulating fatty acids in liver cirrhosis. Oxidative stress is involved in the pathogenesis of chronic liver disease and fibrosis. Increased oxidative stress with impaired antioxidant status at the systemic level has been described in different chronic liver diseases and negatively influences graft function after liver transplantation (Poli G. 2000, Loguercio C 2003). 7-Ketocholesterol and 7beta-hydroxycholesterol, prototype molecules of free radical-mediated cholesterol oxidation, are very important oxysterols currently accepted as in vivo reliable markers of oxidative stress. High oxysterols plasma levels are associated with an alteration of normal plasma fatty acid pattern in cystic fibrosis (Iuliano 2009). The Model for End-Stage Liver Disease (MELD) score is a common score used routinely to stage liver function in patients with liver cirrhosis (Al Sibae 2010). After ischemia-reperfusion injury at liver transplantation oxidative stress, hepatic endoplasmic reticulum (ER) stress and cholesterol metabolism are interrelated key processes to preserve graft regeneration and function. A blood sample is obtained in each subject to measure MELD score at the first visit and at liver transplantation. Further blood samples are collected at days seven and 30 post transplantation. Blood samples are also obtained from healthy subjects. Liver biopsy samples are obtained from liver transplant donors. Oxidative stress and fatty acids lipidomics are measured to evaluate the actual plasma concentration in liver cirrhosis patients to be compared with healthy controls. Oxidative stress and fatty acids are also analyzed as a function of disease status, and for its influence on transplant outcomes. Lipid metabolism gene and endoplasmic stress reticulum gene expression are evaluated in liver biopsy specimen to study the influence on graft function.

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Study Type : Observational
Estimated Enrollment : 320 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Fatty Acids Lipidome and Oxidative Stress Markers as Indicators of Liver Transplant Outcome
Study Start Date : July 2001
Estimated Primary Completion Date : May 2016
Estimated Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

Liver Cirrhosis
Patient with liver cirrhosis undergoing liver transplant
Liver donors
Subjects eligible for organ explant
Healthy controls

Primary Outcome Measures :
  1. Post operative graft function after liver transplantation [ Time Frame: Change in graft function after 7 and 30 days after liver transplantation ]
    • Multiple lipid metabolism biomarkers (fatty acids, cholesterol and oxysterols) are evaluated in the plasma of liver cirrhosis patients before liver transplantation. A logistic regression model is used to evaluate which of these biomarkers is an independent predictor of graft function

Secondary Outcome Measures :
  1. Early gene expression in the liver graft [ Time Frame: 30 days ]
    Assessment of lipid metabolism-, oxidative stress-, and ER stress-gene expression in graft tissue liver tissue specimens of patients undergoing organ transplantation and their impact on graft function. Lipid metabolism and ER gene expression (genes: LDL-R, HMGCR, CD81, SREBP2, NPC1L1, XBP-1, XBP2, ATF6, GRP78, GRP94, LXR, INSIG1, INSIG2) in liver graft specimens at transplantation before and after ischemia-reperfusion injury; downregulated and upregulated genes are related to early graft function.

Biospecimen Retention:   Samples With DNA
Blood samples and liver biopsy specimens

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 69 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
  1. 150 cirrhotic patients, including Hepatocellular Carcinoma (HCC), Hepatitis C Virus (HCV) positive patients
  2. 80 healthy controls
  3. 100 liver donors

Liver cirrhosis inclusion criteria:

  • subjects with liver cirrhosis eligible for liver transplant, and one MELD score determination performed at least 3 months before liver transplantation

Liver cirrhosis exclusion criteria:

  • liver transplant contraindication and re-transplantation
  • current use of antioxidants and fatty acids supplements

Healthy controls are recruited recruited among the University personnel, after a review of their medical history.

Exclusion criteria for control participants included the use of drugs that affect fatty acids (systemic corticosteroids, isotretinoin, and ursodiol) and/or oxidative stress (antioxidants and hypolipemic drugs).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01389115

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Contact: Stefano Corradini, M.D., Ph.D. +390649972086

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Department of Clinical Medicine Division of Gastroenterology, Sapienza University of Rome Recruiting
Rome, RM, Italy, 00161
Contact: Stefano Corradini, M.D., Ph.D.    +39 06 4997 ext 2086   
Contact: Antonio Molinaro, M.D.    +39 06 4997 ext 2086   
Sub-Investigator: Antonio Molinaro, M.D.         
Liver Transplant Center Paride Stefanini, Sapienza University of Rome Recruiting
Rome, RM, Italy, 00161
Contact: Massimo Rossi, M.D.    +39 3346214536   
Laboratory of Vascular Medicine, Department of Medical Sciences and Biotechnology, Sapienza University of Rome Recruiting
Latina, Italy, 04100
Contact: Luigi Iuliano, M.D.    +39 0773 471046   
Contact: Chiara Zerbinati, Ph.D.    +39 0773 471046   
Principal Investigator: Luigi Iuliano, M.D.         
Sub-Investigator: Chiara Zerbinati, M.D.         
Sponsors and Collaborators
University of Roma La Sapienza
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Principal Investigator: Stefano Corradini, M.D., Ph.D. Sapienza University of Rome

Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Luigi Iuliano, M.D., University of Roma La Sapienza Identifier: NCT01389115     History of Changes
Other Study ID Numbers: Iul_LC
First Posted: July 7, 2011    Key Record Dates
Last Update Posted: December 11, 2015
Last Verified: December 2015
Keywords provided by Luigi Iuliano, University of Roma La Sapienza:
liver cirrhosis
oxidative stress
liver transplant
Additional relevant MeSH terms:
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Liver Cirrhosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Liver Extracts