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

Urea Cycle Disorders Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01195753
• Other study ID #: CCD05
• Status: Terminated
• Phase: Phase 2
• First received: March 2, 2010
• Last updated: February 5, 2016
• Start date: December 2010
• Est. completion date: December 2015

Study information

• Verified date: February 2016
• Source: Cytonet GmbH & Co. KG
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 5 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Urea Cycle Disorders
• Urea Cycle Disorders, Inborn

Intervention

Biological:
• HHLivC
multiple infusion of liver cells

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	University of California	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Cytonet GmbH & Co. KG

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Meyburg J, Das AM, Hoerster F, Lindner M, Kriegbaum H, Engelmann G, Schmidt J, Ott M, Pettenazzo A, Luecke T, Bertram H, Hoffmann GF, Burlina A. One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects. Transplantation. 2009 Mar 15;87(5):636-41. doi: 10.1097/TP.0b013e318199936a. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in 13C urea formation from baseline to 2 and 4 months after first HHLivC infusion		Baseline to 2 and 4 months	Yes
Secondary	Frequency and severity of metabolic crises		6 months	Yes