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

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ClinicalTrials.gov Identifier: NCT01379469
Recruitment Status : Recruiting
First Posted : June 23, 2011
Last Update Posted : June 24, 2019
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

Tracking Information
First Submitted Date  ICMJE June 15, 2011
First Posted Date  ICMJE June 23, 2011
Last Update Posted Date June 24, 2019
Study Start Date  ICMJE January 2012
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2013)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 21, 2011)
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 hepatocyes with PAS+/diastase-resistant globules and/or steady state levels of ATZ by immunoblot analysis.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2011)
  • 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 Measures  ICMJE
 (submitted: June 21, 2011)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency
Official Title  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Alpha-1-antitrypsin Deficiency
  • Liver Cirrhosis
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 21, 2011)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 14 Years to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Adam D Kufen, RN, BS, CCRC 412-692-6558 adam.kufen@chp.edu
Contact: Teresa Arb, RN, BSN, CCRC 314-747-1217 arbt@wustl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01379469
Other Study ID Numbers  ICMJE 201510060-PRO09070279
1R21DK092567-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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.
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE
  • Novartis
  • National Institutes of Health (NIH)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • University of Pittsburgh
Investigators  ICMJE
Principal Investigator: David H. Perlmutter, M.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date June 2019

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