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

Study Overview
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Brief Summary
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Treatment with liver cell infusion for children with urea cycle disorders (UCD).

Detailed Description
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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.

Official Title
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Open, Prospective, Historic-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Infusion of Liver Cell Suspension (HHLivC) in Children With Urea Cycle Disorders.

Conditions
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Urea Cycle Disorders

Intervention / Treatment
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* Biological: HHLivC


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liver Cell Infusion<br> | Biological: HHLivC<br>* multiple infusion of liver cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of metabolic crises |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urea cycle Disorders