A Preliminary Study of the Efficacy and Safety of Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency
Overview
- Phase
- Phase 2
- Intervention
- Drug-Carbamazepine (Tegretol XR)
- Conditions
- Alpha-1-antitrypsin Deficiency
- Sponsor
- Washington University School of Medicine
- Enrollment
- 20
- Locations
- 3
- Primary Endpoint
- The Primary Outcome Will be to Determine the Effect of Carbamazepine on Hepatic ATZ Load.
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
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 .
Detailed Description
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.
Investigators
Eligibility Criteria
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
- •Serum total bilirubin \> 5 mg/dl. INR \> 2.2.
Arms & Interventions
Drug-Carbamazepine (Tegretol XR)
One arm receives Drug-Carbamazepine (Tegretol XR).All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Intervention: Drug-Carbamazepine (Tegretol XR)
Drug-Carbamazepine (Tegretol XR) Placebo
One arm receives Carbamazepine (Tegretol-XR) placebo.All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Intervention: Carbamazepine (Tegretol XR) Placebo
Outcomes
Primary Outcomes
The Primary Outcome Will be to Determine the Effect of Carbamazepine on Hepatic ATZ Load.
Time Frame: 52 weeks
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.
Secondary Outcomes
- For the Secondary Outcomes we Will Determine the Effect of Carbamazepine Treatment on Hepatic Fibrosis.(52 weeks)