Effect of Pioglitazone on Portal and Systemic Hemodynamics in Patients With Advanced Cirrhosis

Cirrhosis Clinical Trial

Official title:

Effect of Pioglitazone on Portal and Systemic Hemodynamics in Patients With Advanced Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00570622
• Other study ID #: CIRRPIO
• Status: Completed
• Phase: Phase 4
• First received: December 10, 2007
• Last updated: November 24, 2008
• Start date: December 2004
• Est. completion date: November 2008

Study information

• Verified date: November 2008
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the response to pioglitazone on the hepatic venous pressure gradient and peripheral vascular responsiveness to vasoconstrictors in patients with advanced (Child´s Grade B or C) cirrhosis.

Description:

Cirrhotic liver disease is associated with portal hypertension including elevated portal pressure as well as hyperdynamic circulation and low peripheral vascular resistance. Endothelial nitric (NO) release is impaired in liver microvasculature, upregulation of eNOS activity in the cirrhotic liver may constitute a new strategy to correct the increased hepatic vascular tone in these patients. In contrary to this impaired endothelium-dependent relaxation (endothelial dysfunction) and NO deficiency in the cirrhotic liver, systemic and splanchnic circulation of cirrhotic patients is characterized by increased vascular tone and hyporesponsiveness to vasoconstrictors. In addition to increasing insulin sensitivity, thiazolidinediones, like pioglitazone decrease oxidative stress and inflammation and improve endothelial function. In a randomized controlled, parallel group double-blind study 20 Patients with advanced (Child´s Grade B or C) liver cirrhosis will receive pioglitazone or placebo for nine days. Portal hemodynamics and forearm blood flow response will be measured at baseline and after pioglitazone/placebo to investigate the effect of pioglitazone in these group of patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cirrhosis, grade B or C (Child-Pugh score)

Exclusion Criteria:

• History of hypersensitivity to the trial drugs and contrast agent or to drugs with a similar chemical structure

• Treatment with vasoactive or non-steroidal anti-inflammatory drugs or systemic antibiotics one week before the study

• Exclusion criteria for hepatic hemodynamic investigation

• Cardiac, renal or respiratory failure

• Previous surgical or transjugular intrahepatic portosystemic shunt

• Insulin-dependent diabetes

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ascites
• Cirrhosis
• Hypertension, Portal
• Liver Cirrhosis
• Portal Hypertension

Intervention

Drug:
• Pioglitazone
Patients receive 60mg of pioglitazone once a day orally for 9 days
• Placebo
Patients receive placebo once a day orally for 9 days

Locations

Country	Name	City	State
Austria	Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

References & Publications (1)

Ferlitsch A, Pleiner J, Mittermayer F, Schaller G, Homoncik M, Peck-Radosavljevic M, Wolzt M. Vasoconstrictor hyporeactivity can be reversed by antioxidants in patients with advanced alcoholic cirrhosis of the liver and ascites. Crit Care Med. 2005 Sep;33(9):2028-33. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	portal and systemic hemodynamic parameters		9 days	No
Secondary	markers of oxidative stress (malondialdehyde)		9 days	No