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Fatty Acids Lipidome and Oxidative Stress in Liver Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Roma La Sapienza
Sponsor:
Information provided by (Responsible Party):
Luigi Iuliano, University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT01389115
First received: May 6, 2011
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

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
Liver Cirrhosis

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Fatty Acids Lipidome and Oxidative Stress Markers as Indicators of Liver Transplant Outcome

Resource links provided by NLM:


Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:
  • Post operative graft function after liver transplantation [ Time Frame: Change in graft function after 7 and 30 days after liver transplantation ] [ Designated as safety issue: No ]
    • 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:
  • Early gene expression in the liver graft [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 320
Study Start Date: July 2001
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Liver Cirrhosis
Patient with liver cirrhosis undergoing liver transplant
Liver donors
Subjects eligible for organ explant
Healthy controls

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.

  Eligibility

Ages Eligible for Study:   15 Years to 69 Years
Genders Eligible for Study:   Both
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
Criteria

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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01389115

Contacts
Contact: Stefano Corradini, M.D., Ph.D. +390649972086 stefano.corradini@uniroma1.it

Locations
Italy
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    Stefano.Corradini@uniroma1.it   
Contact: Antonio Molinaro, M.D.    +39 06 4997 ext 2086    antoniomolinaro83@libero.it   
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    massimo.rossi@uniroma1.it   
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    luigi.iuliano@uniroma1.it   
Contact: Roberto Monticolo, Ph.D.    +39 0773 471046    alessandropagnanelli@libero.it   
Principal Investigator: Luigi Iuliano, M.D.         
Sub-Investigator: Roberto Monticolo, M.D.         
Sponsors and Collaborators
University of Roma La Sapienza
Investigators
Principal Investigator: Stefano Corradini, M.D., Ph.D. Sapienza University of Rome
  More Information

Publications:

Responsible Party: Luigi Iuliano, M.D., University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT01389115     History of Changes
Other Study ID Numbers: Iul_LC
Study First Received: May 6, 2011
Last Updated: January 30, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by University of Roma La Sapienza:
liver cirrhosis
oxidative stress
liver transplant

Additional relevant MeSH terms:
Liver Cirrhosis
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on November 24, 2014