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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cirrhosis, Ascites, Portal Hypertension

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Patients receive 60mg of pioglitazone once a day orally for 9 days | Drug: Pioglitazone<br>* Patients receive 60mg of pioglitazone once a day orally for 9 days<br>|
| Placebo Comparator: 2<br>Patients receive Placebo orally once a day for 9 days | Drug: Placebo<br>* Patients receive placebo once a day orally for 9 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| portal and systemic hemodynamic parameters |  | 9 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| markers of oxidative stress (malondialdehyde) |  | 9 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis, oxidative stress, pioglitazone