Hepatocyte Transplantation for Liver Based Metabolic Disorders

NCT01345578 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PRO09040497
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Diseases

Keywords

Urea Cycle Disorders; Carbamoyl-Phosphate Synthase I Deficiency Disease; Citrullinemia; Ornithine Carbamoyltransferase Deficiency Disease; Crigler-Najjar Syndrome

Outcome Measures

Primary Outcomes (1)

• Improvement in enzyme physiologic function at 6 months

  After infusing donor allogeneic hepatocytes through the portal vein following preparative hepatic irradiation, improvement in enzyme physiologic function will be assessed at 6 months.

  6 months post hepatocyte transplant

Study Arms (1)

Hepatocyte Transplantation

EXPERIMENTAL

See Below

Drug: human hepatocyte transplantation; Radiation: Preparative Radiation Therapy

Interventions

human hepatocyte transplantation DRUG

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.

Also known as: hepatocyte transplant

Hepatocyte Transplantation

Preparative Radiation Therapy RADIATION

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).

Hepatocyte Transplantation

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Subject has active malignancy.
• Subject has allergy to immunosuppression medications that are required post transplant procedure for the prevention of rejection.
• Subject has sepsis, pneumonia, other active infection or other secondary life-threatening organ dysfunction.
• 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.
• Subject is pregnant or breastfeeding.

Sponsors & Collaborators

• Ira Fox: lead

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15201, United States

Location

Related Publications (6)

• Horslen SP, Fox IJ. Hepatocyte transplantation. Transplantation. 2004 May 27;77(10):1481-6. doi: 10.1097/01.tp.0000113809.53415.c2.

  PMID: 15239608 BACKGROUND

• Horslen SP, McCowan TC, Goertzen TC, Warkentin PI, Cai HB, Strom SC, Fox IJ. Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. Pediatrics. 2003 Jun;111(6 Pt 1):1262-7. doi: 10.1542/peds.111.6.1262.

  PMID: 12777539 BACKGROUND

• Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, Dorko K, Sauter BV, Strom SC. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med. 1998 May 14;338(20):1422-6. doi: 10.1056/NEJM199805143382004. No abstract available.

  PMID: 9580649 BACKGROUND

• Dhawan A, Mitry RR, Hughes RD, Lehec S, Terry C, Bansal S, Arya R, Wade JJ, Verma A, Heaton ND, Rela M, Mieli-Vergani G. Hepatocyte transplantation for inherited factor VII deficiency. Transplantation. 2004 Dec 27;78(12):1812-4. doi: 10.1097/01.tp.0000146386.77076.47.

  PMID: 15614156 BACKGROUND

• Sokal EM, Smets F, Bourgois A, Van Maldergem L, Buts JP, Reding R, Bernard Otte J, Evrard V, Latinne D, Vincent MF, Moser A, Soriano HE. Hepatocyte transplantation in a 4-year-old girl with peroxisomal biogenesis disease: technique, safety, and metabolic follow-up. Transplantation. 2003 Aug 27;76(4):735-8. doi: 10.1097/01.TP.0000077420.81365.53.

  PMID: 12973120 BACKGROUND

• Jorns C, Ellis EC, Nowak G, Fischler B, Nemeth A, Strom SC, Ericzon BG. Hepatocyte transplantation for inherited metabolic diseases of the liver. J Intern Med. 2012 Sep;272(3):201-23. doi: 10.1111/j.1365-2796.2012.02574.x. Epub 2012 Aug 20.

  PMID: 22789058 DERIVED

MeSH Terms

Conditions

Metabolic Diseases; Urea Cycle Disorders, Inborn; Carbamoyl-Phosphate Synthase I Deficiency Disease; Citrullinemia; Ornithine Carbamoyltransferase Deficiency Disease; Crigler-Najjar Syndrome

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Genetic Diseases, X-Linked; Hyperbilirubinemia, Hereditary

Study Officials

• Ira J Fox, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: April 26, 2011
• First Posted: May 2, 2011
• Study Start: March 1, 2011
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: December 7, 2022

Record last verified: 2022-12

Locations

US (1)