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

This study is currently recruiting participants.

See

Contacts and Locations

Verified May 2017 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: May 10, 2017

Last verified: May 2017

History of Changes

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 Intervention Model: Parallel Assignment Masking: Participant, Care Provider, 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: North American Indian childhood cirrhosis alpha-1 antitrypsin deficiency

MedlinePlus related topics: Alpha-1 Antitrypsin Deficiency Liver Diseases

Drug Information available for: Carbamazepine alpha 1-Antitrypsin Carbamazepine dihydrate

Genetic and Rare Diseases Information Center resources: Alpha-1 Antitrypsin Deficiency

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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.


Estimated Enrollment:	30
Study Start Date:	January 2012
Estimated Study Completion Date:	January 2019
Estimated Primary Completion Date:	January 2019 (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: Tegretol-XR Carbamazepine extended release tablets. NDC 0078-0510-05.
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.

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:

Tegretol-XR Carbamazepine extended release tablets.
NDC 0078-0510-05.

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 (Child, Adult, Senior)
Sexes Eligible for Study:	All
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

Contacts


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

Locations


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 radaket@wustl.edu
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 squiresr@upmc.edu
Contact: Adam D Kufen, RN 412-692-8929 adam.kufen@chp.edu
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.perlmutter@chp.edu
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.

Sponsors and Collaborators

Washington University School of Medicine

Novartis

National Institutes of Health (NIH)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

University of Pittsburgh

Investigators


Principal Investigator:	David H. Perlmutter, M.D.	Washington University School of Medicine

More Information

Additional Information:

Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency This link exits the ClinicalTrials.gov site

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Silverman GA, Pak SC, Perlmutter DH. Disorders of protein misfolding: alpha-1-antitrypsin deficiency as prototype. J Pediatr. 2013 Aug;163(2):320-6. doi: 10.1016/j.jpeds.2013.03.077. Epub 2013 May 8.


Responsible Party:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT01379469 History of Changes
Other Study ID Numbers:	201510060-PRO09070279 1R21DK092567-01 ( US NIH Grant/Contract Award Number )
Study First Received:	June 15, 2011
Last Updated:	May 10, 2017
Individual Participant Data
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.

Keywords provided by Washington University School of Medicine:


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 Diseases Liver Cirrhosis Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Subcutaneous Emphysema Emphysema Pathologic Processes Carbamazepine Anticonvulsants Antimanic Agents	Tranquilizing Agents Central Nervous System Depressants Physiological Effects of Drugs Psychotropic Drugs Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Cytochrome P-450 CYP3A Inducers Cytochrome P-450 Enzyme Inducers Molecular Mechanisms of Pharmacological Action Trypsin Inhibitors Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on June 21, 2017

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