Clinical trial NCT00588302: Moexipril for Primary Biliary Cirrhosis
Official title: Open-Label Pilot Investigation of Moexipril for the Treatment of Primary Biliary Cirrhosis (PBC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Biliary Cirrhosis
Keywords: primary biliary cirrhosis
ursodeoxycholic acid
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: UCB Pharma
First posted: 2008-01-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: change in liver biochemistries and Mayo risk score for PBC
timeFrame: 12 months
Secondary outcomes:
measure: change in health-related quality of life in PBC
timeFrame: 12 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic and Foundation
name: Keith D Lindor, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Talwalkar JA, Lindor KD. Primary biliary cirrhosis. Lancet. 2003 Jul 5;362(9377):53-61. doi: 10.1016/S0140-6736(03)13808-1.