Alpha-1 Study Toolkit for Physicians

A Preliminary Study of the Efficacy and Safety of Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency

Thank you for your interest in this study. Alpha-1 antitrypsin deficiency (ATD) is a genetic condition that can cause liver disease in children and adults as well as serious lung disease in adults. ATD occurs when there is a lack of protein in the blood called alpha-1 antitrypsin (AT). Produced by the liver, the main function of AT is to protect the lungs from inflammation caused by infection and inhaled irritants.

ATD affects 1 in 2,000 births. The resultant liver scarring is the most common genetic cause for which children undergo liver transplantation, presently the only therapeutic option. However, laboratory work has demonstrated that a drug called carbamazepine may help, and may have the potential to reverse fibrosis. Carbamazepine (also known by the brand name Tegretol) is presently used to treat seizure disorders, and it is well understood by the medical community. This has helped enable Children’s Hospital of Pittsburgh of UPMC to initiate this study, which is supported by the National Institutes of Health and Novartis.

Our study is currently enrolling male and female candidates ages 14 and up who have been diagnosed with liver disease due to ATD. For more complete information about the study and to learn how to enroll your patients, please see this Letter to Physicians (PDF).

Patient Outreach

Below are links to additional information about ATD to help with patient education and enrollment in this study.

If you wish to refer a patient to the study, please:

• Review the Key Study Points (PDF) with the child’s parents or, in the case of an adult candidate, with the patient.
• Call the ATD Study support line 1-855-428-2281.
• Provide parents with the Alpha-1 Parent Letter (PDF). For non-pediatric candidates, please provide the Alpha-1 Patient Letter (PDF).
• Someone from the study team will contact the family or individual to schedule an appointment at the hospital where the patient and medical history will be reviewed and details of the study will be explained.

You may also post copies of the Alpha-1 Study Informational Flier (PDF) within your practice.

Additional Resources

• Study Description at National Institutes of Health
• News Release about this Study

Informed Consent Forms

• Pediatric Patient Screening (PDF)
• Pediatric Patient Study Participation (PDF)
• Adult Patient Screening (PDF)
• Adult Patient Study Participation (PDF)

Related Publications

Several published works about this investigation are listed below. Review a complete list of published works about this investigation.

• Science: An autophagy-enhancing drug promotes degradation of mutant α-antitrypsin Z and reduces hepatic fibrosis
• PLOS ONE: Fluphenazine reduces protetotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency
• Pediatric Research: Targeting intracellular degradation pathways for treatment of childhood liver disease due to α1-antitrypsin deficiency (PDF)
• BioMed Research International: Capitalizing on the autophagic response for treatment of liver disease caused by alpha-1-antitrypsin deficiency and other genetic diseases