Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency (CBZ)
This study is currently recruiting participants.
(see Contacts and Locations)
Verified December 2014 by University of Pittsburgh
Sponsor:
University of Pittsburgh
Collaborators:
Novartis
Information provided by (Responsible Party):
David Perlmutter, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01379469
First received: June 15, 2011
Last updated: December 2, 2014
Last verified: December 2014
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Purpose
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 .
| Condition | Intervention | Phase |
|---|---|---|
|
Alpha-1-antitrypsin Deficiency Liver Cirrhosis |
Drug: Drug-Carbamazepine (Tegretol XR) Drug: Carbamazepine (Tegretol XR) Placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Preliminary Study of the Efficacy and Safety of Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency |
Resource links provided by NLM:
Genetics Home Reference related topics:
alpha-1 antitrypsin deficiency
North American Indian childhood cirrhosis
U.S. FDA Resources
Further study details as provided by University of Pittsburgh:
Primary Outcome Measures:
- 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.
Secondary Outcome Measures:
- 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.
| Estimated Enrollment: | 30 |
| Study Start Date: | January 2012 |
| Estimated Study Completion Date: | January 2017 |
| Estimated Primary Completion Date: | January 2017 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
Other Names:
|
|
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.
|
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.
Eligibility| Ages Eligible for Study: | 14 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01379469
Please refer to this study by its ClinicalTrials.gov identifier: NCT01379469
Contacts
| Contact: Adam D Kufen, RN, BS, CCRC | 412-692-6558 | adam.kufen@chp.edu | |
| Contact: Donna Smith, RRT, MS | 412-692-6092 | Donna.Smith@chp.edu |
Locations
| United States, Pennsylvania | |
| Children's Hospital of Pittsburgh, UPMC | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15201 | |
| Contact: David H Perlmutter, M.D. 412-692-8071 David.perlmutter@chp.edu | |
| Principal Investigator: David H. Perlmutter, M.D. | |
| Sub-Investigator: Robert H. Squires, JR., M.D. | |
| Sub-Investigator: Benjamin Shneider, 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.perlmutter@chp.edu | |
| Principal Investigator: David H. Perlmutter, M.D. | |
| Sub-Investigator: George Michalopoulos, M.D., PhD. | |
| Sub-Investigator: Albert Zajko, M.D. | |
| Sub-Investigator: Kapil Chopra, M.D. | |
Sponsors and Collaborators
University of Pittsburgh
Novartis
Investigators
| Principal Investigator: | David H. Perlmutter, M.D. | Children's Hospital of Pittsburgh,UPMC |
More Information
Additional Information:
Publications:
Burroughs A.K., and Thalheimer U., Hepatic venous pressure gradient in 2010: optimal measurement is key. Hepatology. 51: 1894-6.
Dodson W., Carbamazepine and oxycarbazepine, Pediatric Epilepsy: Diagnosis and Therapy, P.J. Dodson W.E., Editor. 1993; Demos Publications: New York. 303-314.
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | David Perlmutter, Principal Investigator, Physician-in-Chief and Scientific Director Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh |
| ClinicalTrials.gov Identifier: | NCT01379469 History of Changes |
| Other Study ID Numbers: | PRO09070279, 1R21DK092567-01 |
| Study First Received: | June 15, 2011 |
| Last Updated: | December 2, 2014 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by University of Pittsburgh:
|
Carbamazepine (Tegretol) use severe liver disease alpha-1-antitrypsin deficiency |
Additional relevant MeSH terms:
|
Alpha 1-Antitrypsin Deficiency Alpha 1-Antitrypsin Protein C Inhibitor Liver Cirrhosis Liver Diseases Digestive System Diseases Emphysema Genetic Diseases, Inborn Lung Diseases Pathologic Processes Respiratory Tract Diseases Subcutaneous Emphysema Carbamazepine Analgesics Analgesics, Non-Narcotic |
Anticonvulsants Antimanic Agents Central Nervous System Agents Central Nervous System Depressants Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs Protease Inhibitors Psychotropic Drugs Sensory System Agents Serine Proteinase Inhibitors Therapeutic Uses Tranquilizing Agents |
ClinicalTrials.gov processed this record on February 25, 2015