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

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.

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

Study Overview

• Status: Terminated
• Conditions: Urea Cycle Disorders
• Intervention / Treatment: Biological: HHLivC

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92103
      • University of California
  • Connecticut
    • New Haven, Connecticut, United States, 06250
      • Yale University
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liver Cell Infusion	Biological: HHLivC; multiple infusion of liver cells

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Cytonet GmbH & Co. KG

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: March 2, 2010
• First Submitted That Met QC Criteria: September 3, 2010
• First Posted (Estimate): September 6, 2010

Study Record Updates

• Last Update Posted (Estimate): February 8, 2016
• Last Update Submitted That Met QC Criteria: February 5, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Urea cycle Disorders
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Disease; Urea Cycle Disorders, Inborn
• Other Study ID Numbers: CCD05