Clinical trial NCT00570622: Effect of Pioglitazone on Portal and Systemic Hemodynamics in Patients With Advanced Cirrhosis
Official title: Effect of Pioglitazone on Portal and Systemic Hemodynamics in Patients With Advanced Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cirrhosis
Ascites
Portal Hypertension
Keywords: Cirrhosis
oxidative stress
pioglitazone
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2007-12-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: portal and systemic hemodynamic parameters
timeFrame: 9 days
Secondary outcomes:
measure: markers of oxidative stress (malondialdehyde)
timeFrame: 9 days
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna
Study officials:
affiliation: Medical University of Vienna
name: Arnulf Ferlitsch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1097/01.ccm.0000178173.27923.eb.