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

Phase 2

Terminated

• Conditions: Alpha-1-antitrypsin Deficiency; Liver Cirrhosis
• Interventions: Drug: Drug-Carbamazepine (Tegretol XR); Drug: Carbamazepine (Tegretol XR) Placebo

• Registration Number: NCT01379469
• Lead Sponsor: Washington University School of Medicine

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2011-06-15
• Study First Submitted QC: 2011-06-21
• Study First Posted: 2011-06-23
• Study Start: 2012-01
• Primary Completion: 2017-02
• Study Completion: 2017-02
• Results First Submitted: 2021-09-09
• Status Verified: 2021-10
• Results First Submitted QC: 2021-10-07
• Last Update Submitted: 2021-10-07
• Results First Posted: 2021-10-12
• Last Update Posted: 2021-10-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 20

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.

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Exclusion Criteria

• Child Pugh Score greater than or equal to 12. Serum total bilirubin > 5 mg/dl. INR > 2.2.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Drug-Carbamazepine (Tegretol XR)	Drug-Carbamazepine (Tegretol XR)	One arm receives Drug-Carbamazepine (Tegretol XR).All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Drug-Carbamazepine (Tegretol XR) Placebo	Carbamazepine (Tegretol XR) Placebo	One arm receives Carbamazepine (Tegretol-XR) placebo.All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.

Primary Outcome Measures

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

Name	Time	Method
For the Secondary Outcomes we Will Determine the Effect of Carbamazepine Treatment on Hepatic Fibrosis.	52 weeks	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.

Trial Locations

Locations (3)

Washington University in St. Louis School of Medicine; 🇺🇸 Saint 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