Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency

Phase 2TerminatedNCT01379469

Washington University School of Medicine20 enrolled

Overview

The primary objective is to determine if the medication Carbamazepine, can be used as a therapy for patients with severe liver disease due to Alpha-1-Antitrypsin Deficiency .

The primary objective is to determine if Carbamazepine therapy in patients with severe liver disease due to Alpha-1-Antitrypsin Deficiency leads to a significant reduction in the hepatic accumulation of ATZ. The other objectives are: To determine whether Carbamazepine treatment reduces hepatic fibrosis in alpha-1-antitrypsin deficient patients with severe liver disease. To determine whether Carbamazepine treatment reduces portal pressure in alpha-1-antitrypsin deficient patients with severe liver disease. To determine whether Carbamazepine treatment is safe and tolerated by patients with severe liver disease caused by alpha-1-deficiency. To determine whether Carbamazepine treatment leads to stabilization in disease severity as measured by the MELD scores.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Alpha-1-antitrypsin Deficiency Liver Cirrhosis

Interventions

Drug-Carbamazepine (Tegretol XR)DRUG

To reduce the likelihood of hypersensitivity reactions the subjects will be started on 400 mg/day in 2 doses and the dose will be increased weekly by 200mg/day until reaching a stable therapeutic concentration with a dose not exceeding 1200mg/day(or 1000mg/day in subjects less than 15 years of age). The CBZ tablets will be encapsulated..

Carbamazepine (Tegretol XR) PlaceboDRUG

Carbamazepine (Tegretol XR)Placebo-the subjects will be started on 400mg/day in 2 doses and the dose will be increased weekly by 200 mg/day until reaching a dose not exceeding 1200 mg/day (or 1000 mg/day in subjects less than 15 years of age). The placebo group will receive encapsulated tables without Carbamazepine.

Eligibility

Sex: ALLMin age: 14 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age greater than or equal to 14 years to less than or equal to 80 years of age. * Alpha-1-Antitrypsin deficiency confirmed by ZZ or SZ phenotype \& serum level * \< 83mg/dl. * HVPG greater than or equal to 10 mmHg unless collateral vessels are visualized via transvenous biopsy. Exclusion Criteria: * Child Pugh Score greater than or equal to 12. Serum total bilirubin \> 5 mg/dl. INR \> 2.2.

Locations (3)

Washington University in St. Louis School of Medicine

St Louis, Missouri, United States

Children's Hospital of Pittsburgh, UPMC

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center, Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

Outcomes

Primary Outcomes

The Primary Outcome Will be to Determine the Effect of Carbamazepine on Hepatic ATZ Load.

The effect of Carbamazepine on hepatic ATZ load will be measured by the number of hepatocytes with PAS+/diastase-resistant globules and/or steady state levels of ATZ by immunoblot analysis.

Time frame: 52 weeks

Secondary Outcomes

For the Secondary Outcomes we Will Determine the Effect of Carbamazepine Treatment on Hepatic Fibrosis.

For the secondary outcomes we will determine the effect of Carbamazepine treatment on hepatic fibrosis on the basis of sirius red staining and hydroxyproline concentration and whether Carbamazepine treatment changes portal pressure as determined by Hepatic Venous Pressure Gradient.

Time frame: 52 weeks

Data from ClinicalTrials.gov

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