Moexipril for Primary Biliary Cirrhosis

NCT ID: NCT00588302

Last Updated: 2011-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2007-06-30

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A, 1

All patients received an open-label moexipril during the study period.

Group Type: EXPERIMENTAL

Moexipril

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• PBC patients treated with UDCA (daily dose of 13 to 15 mg/kg for at least 6 months) and an incomplete response defined by persistent elevation of serum alkaline phosphatase activity at least 2 times the upper limit of normal

Exclusion Criteria

• age less than 18 years
• pregnancy or nursing
• anticipated need for liver transplantation within 1 year with less than a 80% one-year survival determined by the Mayo risk score
• complications of cirrhosis such as recurrent variceal hemorrhage, portosystemic encephalopathy, and refractory ascites
• history of coexistent severe cardiovascular disease including aortic stenosis
• history of coexistent severe renal disease (defined as elevation of serum creatinine more than 1.5 mg/dL) including renal artery stenosis
• history of allergy to ACE inhibitors
• current use of an ACE inhibitors or AT1 receptor antagonists in the past 3 months
• previous treatment with immunosuppressive agents or any experimental drug in the preceding 3 months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UCB Pharma

INDUSTRY

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Principal Investigators

Keith D Lindor, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic and Foundation

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

Talwalkar JA, Lindor KD. Primary biliary cirrhosis. Lancet. 2003 Jul 5;362(9377):53-61. doi: 10.1016/S0140-6736(03)13808-1.

Reference Type: BACKGROUND

PMID: 12853201 (View on PubMed)

Other Identifiers

1032-03

Identifier Type: -

Identifier Source: org_study_id