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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Preliminary Study of the Efficacy and Safety of Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency

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 Summary:

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.

Sponsor: Washington University School of Medicine

Current Primary Outcome: The primary outcome will be to determine the effect of Carbamazepine on hepatic ATZ load. [ Time Frame: 52 weeks ]

Original Primary Outcome: The primary outcome will be to determine the effect of Carbamazepine on hepatic ATZ load. [ Time Frame: 52 weeks ]

Current Secondary Outcome:

• For the secondary outcomes we will determine the effect of Carbamazepine treatment on hepatic fibrosis. [ Time Frame: 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.
• For the secondary outcome we will determine if Carbamazepine treatment reduces the MELD score. [ Time Frame: 52 weeks. ]
  This will be determined by monitoring the MELD score at the beginning and end of the 12-month treatment period, including measuring at seven follow-up visits while on active medication or placebo. The change in MELD score for subjects on active medication will be compared to that in subjects on placebo.Safety and tolerability will be investigated by close observation and routine laboratory testing of the 30 subjects.

Original Secondary Outcome:

• For the secondary outcomes we will determine the effect of Carbamazepine treatment on hepatic fibrosis. [ Time Frame: 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/or hydroxyproline concentration.
• For the secondary outcomes we will determine the effect of Carbamazepine treatment on hepatic portal pressure. [ Time Frame: 52 weeks ]
  Pre and post measurement of Hepatic Venous Pressure Gradient (HVPG), will determine if Carbamazepine treatment changes hepatic portal pressure.
• For the secondary outcomes we will determine safety and tolerability of Carbamazepine treatment. [ Time Frame: 52 weeks. ]
  This will be measured by recording clinical adverse events or laboratory value abnormalities requiring treatment reduction or discontinuation. The number of adverse events, number and percentage of subjects with adverse events, and rates per person-months will be recorded.

Information By: Washington University School of Medicine

Dates:
Date Received: June 15, 2011
Date Started: January 2012
Date Completion: January 2019
Last Updated: May 10, 2017
Last Verified: May 2017