NCT00588302

Moexipril for Primary Biliary Cirrhosis

Open-Label Pilot Investigation of Moexipril for the Treatment of Primary Biliary Cirrhosis (PBC)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The blockade of angiotensin II synthesis attenuates hepatic fibrosis in different experimental models of chronic liver injury. We aimed to determine the safety and efficacy of moexipril, an angiotensin-converting enzyme (ACE) inhibitor, on liver biochemistries, Mayo risk score, and health-related quality of life in patients with primary biliary cirrhosis (PBC) who have had a suboptimal response to ursodeoxycholic acid (UDCA).

Detailed description

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of presumed autoimmune cause characterized by progressive inflammatory destruction of interlobular and septal bile ducts, resulting in fibrosis and eventual cirrhosis (1). In PBC patients, the most disabling symptoms are fatigue and pruritus which diminish health-related quality of life (HRQL. Ursodeoxycholic acid (UDCA), at a dose of 13 to 15 mg/kg per day, is a safe and effective medical therapy for most patients with PBC. Nevertheless, UDCA therapy has not ameliorated symptoms associated with PBC. Some UDCA-treated patients show progressive disease resulting in the liver transplantation or death from liver-related causes. For these patients, who show a persistent elevation of serum alkaline phosphatase at least twice the normal level after 6 months of UDCA monotherapy (incomplete responders), the evaluation of combination therapy in clinical trials has been recommended. Moexipril is a long-acting, nonsulfhydryl ACE inhibitor with lipophilicity, and so can readily penetrate lipid membranes and thus target tissue ACE in addition to plasma ACE. This drug also demonstrated antioxidative properties in addition to efficiently controlling blood pressure in hypertensive postmenopausal subjects. Moreover, quality-of-life data suggest favorable effects of moexipril treatment in a patient population at high cardiovascular risk. The tolerability and safety profile of moexipril resembles that of other ACE inhibitors along with no reports of hepatotoxicity in controlled trials. Hence, moexipril is an attractive drug for evaluation in patients with chronic liver disease.

Conditions

• Primary Biliary Cirrhosis

Interventions

Type	Name	Description
DRUG	Moexipril	Moexipril was given at a starting dose of 7.5 mg daily for 1 week to all enrolled patients. If tolerated (no clinically significant hypotension or medication associated adverse event), the daily dosage was increased to 15 mg daily at the beginning of the 2nd treatment week. Patients took moexipril orally in the morning and 1 hour prior to food intake. The target dose was maintained for the 1-year period of the study unless the development of toxicities warranted dose reduction or discontinuation.

Timeline

• Start date: 2003-06-01
• Primary completion: 2007-06-01
• Completion: 2007-06-01
• First posted: 2008-01-08
• Last updated: 2011-05-23

Locations

1 site across 1 country: United States