Role Of Angiogenic Factors In The Development Of Hepatorenal Syndrome

Liver Diseases Clinical Trial

Official title:

Role Of Angiogenic Factors In The Development Of Hepatorenal Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00734136
• Other study ID #: 2005-040
• Status: Terminated
• Phase: N/A
• First received: August 12, 2008
• Last updated: February 17, 2009
• Start date: May 2005
• Est. completion date: February 2009

Study information

• Verified date: February 2009
• Source: Lahey Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: February 2009
• Est. primary completion date: July 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hepatorenal Syndrome
• Liver Diseases
• Renal Failure
• Renal Insufficiency
• Syndrome

Intervention

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)
• 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

Locations

Country	Name	City	State
United States	Lahey Clinic, Inc.	Burlington	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Lahey Clinic	Beth Israel Deaconess Medical Center, Dr. Vikas Sukhatme

Country where clinical trial is conducted

United States, 

References & Publications (1)

Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004 Feb 12;350(7):672-83. Epub 2004 Feb 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analysis of Blood samples for angiogenic factors		1 week	No