Human Heterologous Liver Cells for Infusion in Newborns and Infants With Urea Cycle Disorders - Tabular View

Tracking Information

First Received Date ^ICMJE

July 16, 2008

Last Updated Date

August 25, 2009

Start Date ^ICMJE

July 2008

Estimated Primary Completion Date

July 2010 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]

Original Primary Outcome Measures ^ICMJE

Safety of the application of liver cells, increase in the respective enzyme activity in liver biopsies taken from the explanted organ compared to the enzyme activity in the liver biopsy taken prior to the first liver cell application. [ Time Frame: 7 - 15 weeks ] [ Designated as safety issue: Yes ]

Change History

Complete list of historical versions of study NCT00718627 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Increase in the respective enzyme activity in liver biopsies taken from the explanted organ compared to the enzyme activity in the liver biopsy taken prior to the first liver cell application, safety, metabolic crises, laboratory parameters [ Time Frame: 7-15 weeks ] [ Designated as safety issue: Yes ]

Original Secondary Outcome Measures ^ICMJE

Safety, metabolic crises, laboratory parameters [ Time Frame: 7-15 weeks ] [ Designated as safety issue: Yes ]

Descriptive Information

Brief Title ^ICMJE

Human Heterologous Liver Cells for Infusion in Newborns and Infants With Urea Cycle Disorders

Official Title ^ICMJE

Open, Prospective, Uncontrolled, Multicentre Study to Evaluate The Safety and Efficacy of Multiple Applications of Liver Cell Suspension Into The Portal Vein in Newborns and Infants With Urea Cycle Disorders (UCDs)

Brief Summary

Urea cycle disorders are rare inherited diseases that generally have a poor outcome. In this study, neonates 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.

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.

Study Phase

Phase II

Study Type ^ICMJE

Interventional

Study Design ^ICMJE

Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Condition ^ICMJE

Urea Cycle Disorders
Carbamoylphosphate Synthetase I Deficiency Disease
Ornithine Transcarbamylase Deficiency Disease
Citrullinemia

Intervention ^ICMJE

Biological: Human Heterologous Liver Cells

Study Arms / Comparison Groups

Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

March 2011

Estimated Primary Completion Date

July 2010 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Biochemically proven urea cycle disorder with deficiency of either:
- Carbamoylphosphate synthetase I or
- Ornithine transcarbamylase or
- Argininosuccinate synthase [Citrullinemia]
Age: Neonates and infants within the first 3 months of life
Accessibility of the portal vein
Written informed consent

Exclusion Criteria:

Structural liver disease (cirrhosis, portal hypertension), or venoocclusive diseases
Portal vein thrombosis
Any contraindication for immunosuppression
Presence of acute infection
Live vaccination planned during the course of the study
Severe coagulopathy, cancer, severe systemic or chronic disease other than study indication (urea cycle deficiency)

Gender

Both

Ages

up to 3 Months

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Martin Lindner, MD

+49 6221 56 ext 2311

Martin.Lindner@med.uni-heidelberg.de

Location Countries ^ICMJE

Germany

Administrative Information

NCT ID ^ICMJE

NCT00718627

Responsible Party

Heinz Kriegbaum, PhD, Cytonet GmbH & Co. KG

Study ID Numbers ^ICMJE

CCD02, SELICAII

Study Sponsor ^ICMJE

Cytonet GmbH & Co. KG

Collaborators ^ICMJE

Investigators ^ICMJE

Principal Investigator:

Georg F. Hoffmann, MD

University Children's Hospital, Heidelberg

Information Provided By

Cytonet GmbH & Co. KG

Verification Date

August 2009

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP