Hepatocyte Transplantation for Liver Based Metabolic Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01345578
First received: April 26, 2011
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Metabolic Diseases
Drug: human hepatocyte transplantation
Radiation: Preparative Radiation Therapy
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 10
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)
Arms Assigned Interventions
Experimental: Hepatocyte Transplantation
See Below
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 transplant
Radiation: 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).

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients will have life-threatening liver-based metabolic disorders who are candidates for organ transplantation where hepatocyte transplantation is considered theoretically curative.
  • In addition to child subjects less than 18 years of age, for purposes of this protocol, adults up to age 21 years will be enrolled since this is the upper age limit of patients which are seen at Children's Hospital of Pittsburgh.

Exclusion Criteria:

  • Patients with liver based metabolic disorders not theoretically treatable with organ transplantation.
  • Subjects who meet any of the following criteria will be excluded from participation in this protocol:

    1. Subject has active malignancy.
    2. Subject has allergy to immunosuppression medications that are required post transplant procedure for the prevention of rejection.
    3. Subject has sepsis, pneumonia, other active infection or other secondary life-threatening organ dysfunction.
    4. Significant liver fibrosis determined by biopsy (if clinically indicated). Significant liver fibrosis will be defined by the Ishak Staging, Stage 5: bridges with occasional nodules.
    5. Subject is pregnant or breastfeeding.
  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: NCT01345578

Locations
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    novoselre@upmc.edu   
Contact: Maria Bond    412-692-7133    bondma@upmc.edu   
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         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Ira J Fox, MD University of Pittsburgh
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01345578     History of Changes
Other Study ID Numbers: PRO09040497
Study First Received: April 26, 2011
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Urea Cycle Disorders
Carbamoyl-Phosphate Synthase I Deficiency Disease
Citrullinemia
Ornithine Carbamoyltransferase Deficiency Disease

Additional relevant MeSH terms:
Metabolic Diseases

ClinicalTrials.gov processed this record on October 19, 2014