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

Phase 4

Completed

• Conditions: Cirrhosis; Ascites; Portal Hypertension
• Interventions: Drug: Pioglitazone; Drug: Placebo

• Registration Number: NCT00570622
• Lead Sponsor: Medical University of Vienna

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2004-12
• Study First Submitted: 2007-12-10
• Study First Submitted QC: 2007-12-10
• Study First Posted: 2007-12-11
• Status Verified: 2008-11
• Primary Completion: 2008-11
• Study Completion: 2008-11
• Last Update Submitted: 2008-11-24
• Last Update Posted: 2008-11-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Pioglitazone	Patients receive 60mg of pioglitazone once a day orally for 9 days
2	Placebo	Patients receive Placebo orally once a day for 9 days

Primary Outcome Measures

Name	Time	Method
portal and systemic hemodynamic parameters	9 days

Secondary Outcome Measures

Name	Time	Method
markers of oxidative stress (malondialdehyde)	9 days

Trial Locations

Locations (1)

Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna; 🇦🇹 Vienna, Austria