Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders
|Urea Cycle Disorders Carbamoylphosphate Synthetase I Deficiency Ornithine Transcarbamylase Deficiency Citrullinemia||Biological: Human Heterologous Liver Cells||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open, Prospective, Uncontrolled, Multicentre Study to Evaluate The Safety and Efficacy of Multiple Applications of Liver Cell Suspension Into The Portal Vein in Children With Urea Cycle Disorders (UCDs)|
- Safety of the application of liver cells, safety of the placement of an application catheter to the portal vein. [ Time Frame: 7 - 15 weeks ]
- Changes in 13C urea formation. Changes in the respective enzyme activity in liver biopsies from the explanted organ compared to the enzyme activity in the liver before cell application. [ Time Frame: 7-15 weeks ]
|Study Start Date:||July 2008|
|Study Completion Date:||November 2015|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
|Experimental: HHLivC Therapy Group||
Biological: Human Heterologous Liver Cells
Multiple applications of liver cell suspension for infusion
Urea cycle disorders are rare inherited diseases that generally have a poor outcome, especially with onset of the disease in the neonatal period. UCDs are caused by a deficiency of one of six enzymes responsible for removing ammonia from the bloodstream. Instead of being converted into urea which is removed from the body with the urine, ammonia accumulates in UCD patients leading to brain damage or death. In the light of a mortality rate of > 50% at the age of 10 years the current pharmacological and dietary therapy is of modest success. Furthermore, mental retardation, cerebral palsy and other neurological sequelae are common among surviving patients.
In the last years, orthotopic liver transplantation (OLT) has become the best therapeutic option for UCD with long-term survival rates of about 90%. However, in the first weeks of life OLT still is technically demanding and prone to complications. With larger size of the recipient, the technical problems with OLT decrease considerably. The increased body weight usually achieved at the age of more than 8 weeks is related to a major reduction in transplantation related morbidity. Stabilization of metabolism until the patient can undergo OLT is essential.
In this study, neonates and infants with UCD will be included within the first 3 months of life and will be treated by repetitive application of human liver cells. In the last consequence, the aim of this new therapy option is to supply a sufficient amount of healthy liver cells to compensate for the metabolic defect and to reduce the risk of neurological deterioration while awaiting OLT.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00718627
|University Children's Hospital, Heinrich-Heine University|
|Düsseldorf, Germany, 40225|
|University Children's Hospital|
|Heidelberg, Germany, D-69120|
|Principal Investigator:||Georg Hoffmann, Prof.||University Children's Hospital|