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

Phase 2

Terminated

• Conditions: Urea Cycle Disorders
• Interventions: Biological: HHLivC

• Registration Number: NCT01195753
• Lead Sponsor: Cytonet GmbH & Co. KG

Brief Summary

Treatment with liver cell infusion for children with urea cycle disorders (UCD).

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, young children with UCD 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 First Submitted: 2010-03-02
• Study First Submitted QC: 2010-09-03
• Study First Posted: 2010-09-06
• Study Start: 2010-12
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-05
• Last Update Posted: 2016-02-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Age: birth up to 5 years of age
• Ornithine transcarbamylase deficiency [OTCD], Carbamyl phosphate synthetase I deficiency [CPSD], Argininosuccinate synthetase deficiency [ASSD, Citrullinaemia]
• Written Informed Consent

Exclusion Criteria

• Weight ≤ 3.5 kg
• Presence of acute infection at the time of inclusion
• Severe chronic or systemic disease other than study indication
• Structural liver disease (eg, cirrhosis, portal hypertension)
• Required valproate therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Liver Cell Infusion	HHLivC	-

Primary Outcome Measures

Name	Time	Method
Changes in 13C urea formation from baseline to 2 and 4 months after first HHLivC infusion	Baseline to 2 and 4 months

Secondary Outcome Measures

Name	Time	Method
Frequency and severity of metabolic crises	6 months

Trial Locations

Locations (5)

Yale University; 🇺🇸 New Haven, Connecticut, United States

University of California; 🇺🇸 San Diego, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Children's Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada