Effect of Pioglitazone on Portal and Systemic Hemodynamics in Patients With Advanced Cirrhosis - Full Text View

Sponsor:	Medical University of Vienna
Information provided by:	Medical University of Vienna
ClinicalTrials.gov Identifier:	NCT00570622

Purpose

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.

Condition	Intervention	Phase
Cirrhosis Ascites Portal Hypertension	Drug: Pioglitazone Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Efficacy Study
Official Title:	Effect of Pioglitazone on Portal and Systemic Hemodynamics in Patients With Advanced Cirrhosis

Resource links provided by NLM:

MedlinePlus related topics: Cirrhosis High Blood Pressure

Drug Information available for: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:

portal and systemic hemodynamic parameters [ Time Frame: 9 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

markers of oxidative stress (malondialdehyde) [ Time Frame: 9 days ] [ Designated as safety issue: No ]

Enrollment:	20
Study Start Date:	December 2004
Study Completion Date:	November 2008
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Patients receive 60mg of pioglitazone once a day orally for 9 days	Drug: Pioglitazone Patients receive 60mg of pioglitazone once a day orally for 9 days
2: Placebo Comparator Patients receive Placebo orally once a day for 9 days	Drug: Placebo Patients receive placebo once a day orally for 9 days

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

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570622

Locations

Austria
Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna
Vienna, Austria, 1090

Sponsors and Collaborators

Medical University of Vienna

Investigators

Principal Investigator:

Arnulf Ferlitsch, MD

Medical University of Vienna

More Information

Publications:

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.

Responsible Party:	Gastroenterology and Hepatology, Medical University of Vienna ( Arnulf Ferlitsch, MD )
Study ID Numbers:	CIRRPIO
Study First Received:	December 10, 2007
Last Updated:	November 24, 2008
ClinicalTrials.gov Identifier:	NCT00570622 History of Changes
Health Authority:	Austria: Ethikkommission

Keywords provided by Medical University of Vienna:

Cirrhosis
oxidative stress
pioglitazone

Additional relevant MeSH terms:

Liver Diseases
Pioglitazone
Fibrosis
Physiological Effects of Drugs
Vascular Diseases
Hypertension, Portal
Liver Cirrhosis

Pharmacologic Actions
Digestive System Diseases
Pathologic Processes
Hypoglycemic Agents
Cardiovascular Diseases
Hypertension

ClinicalTrials.gov processed this record on February 08, 2010