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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by University of Pittsburgh
Sponsor:
Collaborators:
Novartis
Information provided by (Responsible Party):
David Perlmutter, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01379469
First received: June 15, 2011
Last updated: February 25, 2013
Last verified: February 2013

June 15, 2011
February 25, 2013
January 2012
January 2014   (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.

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 100 mg 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 2015
January 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age greater than or equal to 14 years.
  • 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 75 Years
No
Contact: Erin K Sandene, BSN, CCRC 412-692-6558 erin.sandene@chp.edu
United States
 
NCT01379469
PRO09070279, 1R21DK092567-01
Yes
David Perlmutter, University of Pittsburgh
University of Pittsburgh
  • Novartis
  • National Institutes of Health (NIH)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: David H. Perlmutter, M.D. Children's Hospital of Pittsburgh,UPMC
University of Pittsburgh
February 2013

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