Role Of Angiogenic Factors In The Development Of Hepatorenal Syndrome

This study has been terminated.
(Insufficient findings for data analysis)
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Dr. Vikas Sukhatme
Information provided by:
Lahey Clinic
ClinicalTrials.gov Identifier:
NCT00734136
First received: August 12, 2008
Last updated: February 17, 2009
Last verified: February 2009
  Purpose

This Study will look at the effect of substances called "angiogenic factors"(development of new blood vessels) have on the development of severe liver disease. The results may help to understand the factors involved in the repair and regeneration of liver tissue and to see if different types of liver disease are associated with different types of factors, especially in the severe liver disease called hepatorenal syndrome.


Condition Intervention
Hepatorenal Syndrome
Renal Failure
Liver Diseases
Procedure: Blood Draws and a hepatectomy specimen
Procedure: Blood draw - pre operative standard of care

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Role Of Angiogenic Factors In The Development Of Hepatorenal Syndrome

Resource links provided by NLM:


Further study details as provided by Lahey Clinic:

Primary Outcome Measures:
  • Analysis of Blood samples for angiogenic factors [ Time Frame: 1 week ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: May 2005
Study Completion Date: February 2009
Primary Completion Date: July 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
50 surgical subjects undergoing either liver transplantation or hepatic resection
Procedure: Blood Draws and a hepatectomy specimen

Pre operative blood draw(1.5 ml serum, 1.5 ml EDTA)(approximately 2 teaspoons).

Blood draw during surgery(1.5 ml serum, 1.5 ml EDTA)from Hepatic Artery, Hepatic Vein, and Portal Vein.

Wedge section of Hepatectomy specimen following resection in surgical subjects(tested for the same factors)

2
50 Subjects with Liver disease who are are not surgical candidates
Procedure: Blood draw - pre operative standard of care
Pre-operative blood draw(1.5 ml serum, 1.5 ml EDTA)(approximately 2 teaspoons) from peripheral vein

Detailed Description:

Renal dysfunction in patients who also suffer from end stage liver disease is associated with increased morbidity and mortality comparted to patients suffering from liver disease alone. If frank renal failure develops in a patient with cirrhosis and ascites, the median survival time from onset of renal failure is approximately 2 weeks. Kidney dysfunction may be transient, secondary to pooling of blood in the splanchnic bed and consequent reduction in renal blood flow. In this instance, liver transplantation and restoration of normal circulatory patterns will result in return of normal renal function.

Currently, there is no diagnostic test to differentiate between temporary and permanent renal dysfunction in the presence of end stage liver disease. As a result, the number of combined liver-kidney transplant occuring has steadily increased. Slightly more than 20%(8 of 38) of the liver transplants performed by our service in 2004 have been combined liver-kidney transplants. The double procedure increases the length of anesthesia exposure and surgical time, and the presence of the transplanted kidney may require increased immunosuppression in comparison to a liver-only transplant.

We plan to examine the role of angiogenic factors in the abnormal blood flow patterns known to be associated with hepatorenal syndrome.

Specimen analysis: Circulating levels of cytokines and growth factors will be measured using commercially available ELISAs. Matrix metalloproteins will be measured by quantitative electrophoresis.

Expression of A20 will be determined by extraction of total RNA from whole blood using Trizol and run in standard Northern blot methodology. RNA will by hybridized with [³²P]-dATP labeled A20 probes and glyceraldehyde-3-phosphate dehydrogenase(GAPDH) or β-actin probes to correct for uneven loading. Similar RNA extraction will be performed on liver tissue obtained at time of surgery. Microarray analysis will be performed on the extract to identify specific genes that may be involved in the pathogenesis of HRS.

Results of laboratory analyses will be correlated with clinical parameters and attempts will be made to identify specific cytokines or up-regulated genes with particular phases or degree or renal dysfunction in patients with liver disease. Similar analyses will be performed in patients with other types of hepatic disease.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Sign informed consent
  • Subjects who present for Liver Transplantation
  • Subjects who present for Hepatic resection
  • Subjects with Non-Surgical Liver Disease

Exclusion Criteria:

  • Absence of Liver Disease
  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: NCT00734136

Locations
United States, Massachusetts
Lahey Clinic, Inc.
Burlington, Massachusetts, United States, 01805
Sponsors and Collaborators
Lahey Clinic
Beth Israel Deaconess Medical Center
Dr. Vikas Sukhatme
Investigators
Principal Investigator: Mary Ann Simpson, Ph.D. Lahey Clinic, Inc.
  More Information

Publications:
Responsible Party: Mary Ann Simpson, Ph.D., Lahey Clinic, Inc.
ClinicalTrials.gov Identifier: NCT00734136     History of Changes
Other Study ID Numbers: 2005-040
Study First Received: August 12, 2008
Last Updated: February 17, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Lahey Clinic:
Angiogenic Factors
Hepatorenal Syndrome
Liver Disease
Renal Failure
Liver Cirrhosis
Ascites

Additional relevant MeSH terms:
Hepatorenal Syndrome
Liver Diseases
Renal Insufficiency
Digestive System Diseases
Kidney Diseases
Urologic Diseases
Angiogenesis Inducing Agents
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 10, 2014