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Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders (SELICA V)

This study is currently recruiting participants.
Verified November 2012 by Cytonet GmbH & Co. KG
Sponsor:
Information provided by (Responsible Party):
Cytonet GmbH & Co. KG
ClinicalTrials.gov Identifier:
NCT00718627
First received: July 16, 2008
Last updated: November 13, 2012
Last verified: November 2012
History of Changes
  Purpose

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 Disease
Ornithine Transcarbamylase Deficiency Disease
Citrullinemia
 Biological: Human Heterologous Liver Cells
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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:

U.S. FDA Resources

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes in 13C urea formation. Increase 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: July 2008
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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.

  Eligibility

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

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
  • Cancer, severe systemic or chronic disease other than study indication (urea cycle deficiency)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00718627

Contacts
Contact: Martin Lindner, MD +49 6221 56 ext 2311 Martin.Lindner@med.uni-heidelberg.de

Locations
Germany
Allgemeine Pädiatrie, Pädiatrische Stoffwechselmedizin Recruiting
Charité Universitätsmedizin Berlin, Berlin, Germany, 13353
Contact: Julia Hennermann, MD         julia.hennermann@charite.de    
Principal Investigator: Julia Hennermann, MD            
University Children's Hospital, Heinrich-Heine University Recruiting
Düsseldorf, Germany, 40225
Principal Investigator: Andrea Schlune, Dr., MD            
Hannover Medical School, Children's Hospital Recruiting
Hannover, Germany, 30625
Principal Investigator: Anibh M. Das, Prof., MD            
University Children's Hospital Recruiting
Heidelberg, Germany, D-69120
Principal Investigator: Georg F. Hoffmann, Prof., MD            
Universitätsklinikum Münster Recruiting
Münster, Germany, 48149
Contact: Thorsten Marquardt, Prof. Dr. med.     +49251-83 ext 48002     thorsten.marquardt@ukmuenster.de    
Principal Investigator: Thorsten Marquardt, Prof., MD            
Sponsors and Collaborators
Cytonet GmbH & Co. KG
Investigators
Principal Investigator: Georg F. Hoffmann, MD University Children's Hospital, Heidelberg
  More Information

No publications provided

Responsible Party: Cytonet GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT00718627     History of Changes
Other Study ID Numbers: CCD02, SELICA V, 2006-000136-27
Study First Received: July 16, 2008
Last Updated: November 13, 2012
Health Authority: Germany: Paul-Ehrlich-Institut

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

Additional relevant MeSH terms:
Deficiency Diseases
Urea Cycle Disorders, Inborn
Citrullinemia
Ornithine Carbamoyltransferase Deficiency Disease
Carbamoyl-Phosphate Synthase I Deficiency Disease
Malnutrition
Nutrition Disorders
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

ClinicalTrials.gov processed this record on May 23, 2013