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

Urea Cycle Disorders Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00718627
• Other study ID #: CCD02
• Secondary ID: CCD022006-000136
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2008
• Last updated: February 5, 2016
• Start date: July 2008
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: Cytonet GmbH & Co. KG
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 5 Years

Eligibility

Inclusion Criteria

• Neonates and infants up to the age of = 3 months with prenatally or postnatally confirmed urea cycle disorder and

• Children aged > 3 months up to = 5 years of age with unstable metabolism and confirmed urea cycle disorder of either:

• Carbamylphosphate synthetase I [CPSD] or

• Ornithine transcarbamylase [OTCD] or

• Argininosuccinate synthetase [Citrullinaemia]

• A DNA analysis will further confirm diagnosis prior to or after inclusion according to the protocol.

• Accessibility of the portal vein

• Plasma ammonia level = 250 µmol/l

• Written informed consent

Exclusion Criteria

• Structural liver disease (cirrhosis, portal hypertension), or venoocclusive diseases

• Portal vein thrombosis

• Body Weight =3.5 kg

• Carrier of the human immuno-deficiency virus (HIV)

• Any other contraindication for immunosuppression

• Presence of acute infection at the time of inclusion

• Participation in other clinical trials or received experimental medication within the last 30 days

• Live vaccination planned during the course of the study

• Live vaccination within 4 weeks prior to beginning of study

• Allergic disposition against contrast medium used in study and/or antibiotics used in the manufacturing process

• Required valproate therapy

• Severe coagulopathy or thrombocytopenia

• Known diagnosis of hereditary thrombophilia (e.g. Factor V Leiden, Prothrombin 20210A variant) or parental history of hereditary thrombophilia and absense of thrombophilia testing in subject

• Cancer, severe systemic or chronic disease other than study indication (urea cycle deficiency)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carbamoyl-Phosphate Synthase I Deficiency Disease
• Carbamoylphosphate Synthetase I Deficiency
• Citrullinemia
• Ornithine Transcarbamylase Deficiency
• Urea Cycle Disorders
• Urea Cycle Disorders, Inborn

Intervention

Biological:
• Human Heterologous Liver Cells
Multiple applications of liver cell suspension for infusion

Locations

Country	Name	City	State
Germany	University Children's Hospital, Heinrich-Heine University	Düsseldorf
Germany	University Children's Hospital	Heidelberg

Sponsors (1)

Lead Sponsor	Collaborator
Cytonet GmbH & Co. KG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of the application of liver cells, safety of the placement of an application catheter to the portal vein.		7 - 15 weeks	Yes
Secondary	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	Yes