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Trial record 1 of 7 for:    "carbamoyl phosphate synthetase I deficiency"
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Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders

This study has been completed.
Information provided by (Responsible Party):
Cytonet GmbH & Co. KG Identifier:
First received: July 16, 2008
Last updated: February 5, 2016
Last verified: February 2016
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.

Condition Intervention Phase
Urea Cycle Disorders
Carbamoylphosphate Synthetase I Deficiency
Ornithine Transcarbamylase Deficiency
Biological: Human Heterologous Liver Cells
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Safety of the application of liver cells, safety of the placement of an application catheter to the portal vein. [ Time Frame: 7 - 15 weeks ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 7-15 weeks ]

Enrollment: 12
Study Start Date: July 2008
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HHLivC Therapy Group Biological: Human Heterologous Liver Cells
Multiple applications of liver cell suspension for infusion

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, 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.


Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)
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Please refer to this study by its identifier: NCT00718627

University Children's Hospital, Heinrich-Heine University
Düsseldorf, Germany, 40225
University Children's Hospital
Heidelberg, Germany, D-69120
Sponsors and Collaborators
Cytonet GmbH & Co. KG
Principal Investigator: Georg Hoffmann, Prof. University Children's Hospital
  More Information

Responsible Party: Cytonet GmbH & Co. KG Identifier: NCT00718627     History of Changes
Other Study ID Numbers: CCD02
CCD02 ( Other Identifier: cytonet )
2006-000136-27 ( EudraCT Number )
Study First Received: July 16, 2008
Last Updated: February 5, 2016

Keywords provided by Cytonet GmbH & Co. KG:
Urea cycle Disorders
Carbamoylphosphate synthetase I deficiency
Ornithine transcarbamoylase deficiency
Argininosuccinate synthase deficiency
liver cell transplantation
liver cell infusion

Additional relevant MeSH terms:
Carbamoyl-Phosphate Synthase I Deficiency Disease
Urea Cycle Disorders, Inborn
Ornithine Carbamoyltransferase Deficiency Disease
Pathologic Processes
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Genetic Diseases, X-Linked
Mitochondrial Diseases
Liver Extracts
Hematinics processed this record on May 25, 2017