Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency (CBZ)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01379469|
Recruitment Status : Recruiting
First Posted : June 23, 2011
Last Update Posted : May 11, 2017
|Condition or disease||Intervention/treatment||Phase|
|Alpha-1-antitrypsin Deficiency Liver Cirrhosis||Drug: Drug-Carbamazepine (Tegretol XR) Drug: Carbamazepine (Tegretol XR) Placebo||Phase 2|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Preliminary Study of the Efficacy and Safety of Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency|
|Study Start Date :||January 2012|
|Estimated Primary Completion Date :||January 2019|
|Estimated Study Completion Date :||January 2019|
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.
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.
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.
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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01379469
|Contact: Adam D Kufen, RN, BS, CCRCemail@example.com|
|Contact: Terri Radake, RN, BSN, CCRCfirstname.lastname@example.org|
|United States, Missouri|
|Washington University in St. Louis School of Medicine||Recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: Terri Radake, RN, BSN, CCRC 314-747-5366 email@example.com|
|Principal Investigator: David A Rudnick, MD, PhD|
|Sub-Investigator: Kevin M. Korenblat, MD|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh, UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15201|
|Contact: Robert H Squires, M.D. 412-692-7506 firstname.lastname@example.org|
|Contact: Adam D Kufen, RN 412-692-8929 email@example.com|
|Principal Investigator: Robert H. Squires, JR., M.D.|
|Sub-Investigator: Alejandro Hoberman, M.D.|
|Sub-Investigator: Ira Bergman, M.D., PhD.|
|Sub-Investigator: Andrew Chu, MD|
|University of Pittsburgh Medical Center, Presbyterian Hospital||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: David H. Perlmutter, M.D. 412-692-8071 David.firstname.lastname@example.org|
|Principal Investigator: Robert H. Squires, M.D.|
|Sub-Investigator: George Michalopoulos, M.D., PhD.|
|Sub-Investigator: Shahid Malik, M.D.|
|Sub-Investigator: Kapil Chopra, M.D.|
|Sub-Investigator: Michael Dunn, M.D.|
|Sub-Investigator: Philip Orons, M.D.|
|Sub-Investigator: Mitchell Tublin, M.D.|
|Sub-Investigator: Allesandro Furlan, M.D.|
|Principal Investigator:||David H. Perlmutter, M.D.||Washington University School of Medicine|