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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Washington University School of Medicine
Sponsor:
Collaborators:
Novartis
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Pittsburgh
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01379469
First received: June 15, 2011
Last updated: June 9, 2016
Last verified: June 2016

June 15, 2011
June 9, 2016
January 2012
January 2017   (final data collection date for primary outcome measure)
The primary outcome will be to determine the effect of Carbamazepine on hepatic ATZ load. [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
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.
The primary outcome will be to determine the effect of Carbamazepine on hepatic ATZ load. [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
The effect of Carbamazepine on hepatic ATZ load will be measured by the number of hepatocyes with PAS+/diastase-resistant globules and/or steady state levels of ATZ by immunoblot analysis.
Complete list of historical versions of study NCT01379469 on ClinicalTrials.gov Archive Site
  • For the secondary outcomes we will determine the effect of Carbamazepine treatment on hepatic fibrosis. [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    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.
  • For the secondary outcomes we will determine the effect of Carbamazepine treatment on hepatic fibrosis. [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    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.
Not Provided
Not Provided
 
Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency
A Preliminary Study of the Efficacy and Safety of Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency
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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Alpha-1-antitrypsin Deficiency
  • Liver Cirrhosis
  • Drug: Drug-Carbamazepine (Tegretol XR)
    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, and the placebo group will receive encapsulated tablets without CBZ.
    Other Names:
    • Tegretol-XR Carbamazepine extended release tablets.
    • NDC 0078-0510-05.
  • Drug: Carbamazepine (Tegretol XR) Placebo
    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.
    Other Name: Carbamazepine (Tegretol-XR) placebo.
  • Active Comparator: 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: Drug-Carbamazepine (Tegretol XR)
  • Placebo Comparator: 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: Drug: Carbamazepine (Tegretol XR) Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
January 2017
January 2017   (final data collection date for primary outcome measure)

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.
Both
14 Years to 80 Years   (Child, Adult, Senior)
No
Contact: Adam D Kufen, RN, BS, CCRC 412-692-6558 adam.kufen@chp.edu
Contact: Terri Radake, RN, BSN, CCRC 314-747-5366 radaket@wustl.edu
United States
 
NCT01379469
201510060-PRO09070279, 1R21DK092567-01
Yes
Yes
We will share data and liver tissue with other researchers. They may be doing research in areas similar to this research or in other unrelated areas. These researchers may be at Washington University, at other research centers and institutions, or industry sponsors of research. We may also share research data with large data repositories (a repository is a database of information) for broad sharing with the research community. If individual research data is placed in one of these repositories only qualified researchers, who have received prior approval from individuals that monitor the use of the data, will be able to look at the information.
Washington University School of Medicine
Washington University School of Medicine
  • Novartis
  • National Institutes of Health (NIH)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • University of Pittsburgh
Principal Investigator: David H. Perlmutter, M.D. Washington University School of Medicine
Washington University School of Medicine
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP