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Hepatocyte Transplantation for Liver Based Metabolic Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01345578
Recruitment Status : Suspended (seeking additional funding)
First Posted : May 2, 2011
Last Update Posted : January 21, 2019
Information provided by (Responsible Party):
Ira Fox, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE April 26, 2011
First Posted Date  ICMJE May 2, 2011
Last Update Posted Date January 21, 2019
Study Start Date  ICMJE March 2011
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 28, 2011)
Improvement in enzyme physiologic function at 6 months [ Time Frame: 6 months post hepatocyte transplant ]
After infusing donor allogeneic hepatocytes through the portal vein following preparative hepatic irradiation, improvement in enzyme physiologic function will be assessed at 6 months.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01345578 on Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Hepatocyte Transplantation for Liver Based Metabolic Disorders
Official Title  ICMJE Hepatocyte Transplantation for Liver Based Metabolic Disorders
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metabolic Diseases
Intervention  ICMJE
  • 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).
Study Arms  ICMJE Experimental: Hepatocyte Transplantation
See Below
  • Drug: human hepatocyte transplantation
  • Radiation: Preparative Radiation Therapy
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: April 28, 2011)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01345578
Other Study ID Numbers  ICMJE PRO09040497
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Ira Fox, University of Pittsburgh
Study Sponsor  ICMJE Ira Fox
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ira J Fox, MD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP