Hepatocyte Transplantation for Liver Based Metabolic Disorders
The purpose of this research study is to determine whether partial irradiation of the liver and liver cell transplantation can provide help for patients with life-threatening liver-based metabolic diseases who are unlikely to survive without extensive medical therapy or transplant. The goal of this research study is to determine if liver cell transplants can be effective as an alternative to organ transplantation. At the present time, liver cell transplants are experimental and have been done in a limited number of human subjects.
Drug: human hepatocyte transplantation
Radiation: Preparative Radiation Therapy
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Hepatocyte Transplantation for Liver Based Metabolic Disorders|
- Improvement in enzyme physiologic function at 6 months [ Time Frame: 6 months post hepatocyte transplant ] [ Designated as safety issue: Yes ]After infusing donor allogeneic hepatocytes through the portal vein following preparative hepatic irradiation, improvement in enzyme physiologic function will be assessed at 6 months.
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||February 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Hepatocyte Transplantation
Drug: human hepatocyte transplantation
Transplantation of hepatocytes into the liver will be through the portal vein. The portal vein will be accessed transhepatically, by umbilical vein, or surgically by a peripheral mesenteric vein.
The subject will be evaluated de novo and if they are a candidate for orthotopic liver transplantation they will receive the transplant. Even if the subject receives the hepatocyte transplant and it does not work, they will be evaluated for orthotopic liver transplantation as if they never received the hepatocyte transplant.
If at 6 months we see an improvement in disease, we will recommend a re-transplantation with a goal of complete correction of disease and until the subject is no longer required to be a candidate for organ transplantation. Subjects will be re-evaluated every 6 months for re-transplantation. Subjects will remain on the waiting list for organ transplantation. Further radiation therapy will not be needed prior to re-transplantation.
Other Name: hepatocyte transplantRadiation: Preparative Radiation Therapy
Just prior to the hepatocyte transplant, a portion of the right hepatic lobe comprising between 35-50% of the entire liver volume will be irradiated to a dose of 7.5-10 Gy in a single fraction using a linear accelerator-based stereotactic radiosurgery system with intensity-modulated radiation therapy planning (IMRT).
Management of patients with hepatic failure and liver-based metabolic disorders is complex and expensive. Hepatic failure results in impaired coagulation, altered consciousness and cerebral function, a heightened risk of multiple organ system failure, and sepsis. Liver transplantation is often the only available treatment option for severe, even if transient, hepatic failure. Patients with life-threatening liver-based metabolic disorders similarly require organ transplantation even though their metabolic diseases are typically the result of a single enzyme deficiency, and the liver otherwise functions normally. More than 17,000 patients currently await liver transplantation in the United States, a number that seriously underestimates the number of patients that need treatment, as it has been estimated that more than a million patients in the United States could benefit from transplantation. Unfortunately, use of whole liver transplantation to treat these disorders is limited by a severe shortage of donors and by the risks associated with major surgery. Hepatocyte transplantation holds great promise as an alternative to organ transplantation for the treatment of liver diseases, and numerous studies in rodents indicate that transplants consisting of isolated liver cells can correct various metabolic deficiencies of the liver and can reverse hepatic failure. The transplant procedure, which involves injection of isolated hepatocytes into the liver through the portal vein, is far less intrusive than transplantation of the whole liver and could be performed on severely ill patients with relatively low risk. In the presence of normal host liver architecture, the transplanted cells integrate into the host liver, providing considerable restorative potential. Because the native liver is not removed, the transplanted hepatocytes need only improve some of the functions of the failing liver and need not replace all hepatic functions. Although clinical trials of hepatocyte transplantation have demonstrated the long-term safety of the procedure, only partial correction of metabolic disorders has been achieved, and the degree to which donor hepatocytes have restored failing livers has not been adequate to circumvent the need for organ replacement.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01345578
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15201|
|Contact: Rachel E Sada, MS, CIP 412-692-7673 firstname.lastname@example.org|
|Contact: Maria Bond 412-692-7133 email@example.com|
|Principal Investigator: Ira J Fox, MD|
|Sub-Investigator: Kyle Soltys, MD|
|Sub-Investigator: George Mazariegos, MD|
|Sub-Investigator: Rakesh Sindhi, MD|
|Sub-Investigator: Geoffrey Bond, MD|
|Sub-Investigator: Gerard Vockley, MD|
|Sub-Investigator: Georgianne Arnold, MD|
|Sub-Investigator: John Crowley, MD|
|Sub-Investigator: Melvin Deutsch, MD|
|Sub-Investigator: Ben Shneider, MD|
|Sub-Investigator: Robert Squires, MD|
|Sub-Investigator: Charles Fitz, MD|
|Sub-Investigator: Robert Stough, MD|
|Sub-Investigator: Miguel Reyes-Mugica, MD|
|Principal Investigator:||Ira J Fox, MD||University of Pittsburgh|