Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders

Phase 2

Completed

• Conditions: Citrullinemia; Urea Cycle Disorders; Carbamoylphosphate Synthetase I Deficiency; Ornithine Transcarbamylase Deficiency
• Interventions: Biological: Human Heterologous Liver Cells

• Registration Number: NCT00718627
• Lead Sponsor: Cytonet GmbH & Co. KG

Brief Summary

Urea cycle disorders are rare inherited diseases that generally have a poor outcome. 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 to reduce the risk of neurological deterioration while awaiting OLT.

Detailed Description

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.

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-07-16
• Study First Submitted QC: 2008-07-17
• Study First Posted: 2008-07-18
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-05
• Last Update Posted: 2016-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HHLivC Therapy Group	Human Heterologous Liver Cells	-

Primary Outcome Measures

Name	Time	Method
Safety of the application of liver cells, safety of the placement of an application catheter to the portal vein.	7 - 15 weeks

Secondary Outcome Measures

Name	Time	Method
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.	7-15 weeks

Trial Locations

Locations (2)

University Children's Hospital; 🇩🇪 Heidelberg, Germany

University Children's Hospital, Heinrich-Heine University; 🇩🇪 Düsseldorf, Germany