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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by Cytonet GmbH & Co. KG
Information provided by (Responsible Party):
Cytonet GmbH & Co. KG Identifier:
First received: March 2, 2010
Last updated: December 9, 2014
Last verified: December 2014

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

Condition Intervention Phase
Urea Cycle Disorders
Biological: HHLivC
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:

Further study details as provided by Cytonet GmbH & Co. KG:

Primary Outcome Measures:
  • Changes in 13C urea formation from baseline to 2 and 4 months after first HHLivC infusion [ Time Frame: Baseline to 2 and 4 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Frequency and severity of metabolic crises [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: December 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Liver Cell Infusion Biological: HHLivC
multiple infusion of liver cells

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.


Ages Eligible for Study:   up to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01195753

Contact: Mark Johnston +1 919 354 1934
Contact: Stefanie Schäfer +49 6201 259 8137

United States, California
Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Andrew Bonham, MD   
Principal Investigator: Andrew Bonham, MD         
University of California Recruiting
San Diego, California, United States, 92103
Contact: Bruce Barshop, MD   
Principal Investigator: Bruce Barshop, MD         
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06250
Contact: Sukru Emre, MD   
Principal Investigator: Sukru Emre, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Miriam Vos, MD   
Principal Investigator: Miriam Vos, MD         
United States, Illinois
Children's Memorial Hospital Recruiting
Chicago, Illinois, United States, 60614
Contact: Barbara Burton, MD   
Principal Investigator: Barbara Burton, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Susan Berry, MD   
Principal Investigator: Susan Berry, MD         
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: George Diaz, MD   
Principal Investigator: George Diaz, MD         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: John Lawrence Merritt III, MD   
Principal Investigator: John Lawrence Merritt III, MD         
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: David Dimmock, MD   
Principal Investigator: David Dimmock, MD         
Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Aneal Khan, MD   
Principal Investigator: Aneal Khan, MD         
Sponsors and Collaborators
Cytonet GmbH & Co. KG
  More Information

Responsible Party: Cytonet GmbH & Co. KG Identifier: NCT01195753     History of Changes
Other Study ID Numbers: CCD05
Study First Received: March 2, 2010
Last Updated: December 9, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Cytonet GmbH & Co. KG:
Urea cycle Disorders

Additional relevant MeSH terms:
Urea Cycle Disorders, Inborn
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases processed this record on March 30, 2015