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

Primary Purpose

Urea Cycle Disorders, Carbamoylphosphate Synthetase I Deficiency, Ornithine Transcarbamylase Deficiency

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Human Heterologous Liver Cells
Sponsored by
Cytonet GmbH & Co. KG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urea Cycle Disorders focused on measuring Urea cycle Disorders, Carbamoylphosphate synthetase I deficiency, Ornithine transcarbamoylase deficiency, Argininosuccinate synthase deficiency, Citrullinemia, newborns, infants, liver cell transplantation, liver cell infusion

Eligibility Criteria

1 Day - 5 Years (Child)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University Children's Hospital, Heinrich-Heine University
  • University Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HHLivC Therapy Group

Arm Description

Outcomes

Primary Outcome Measures

Safety of the application of liver cells, safety of the placement of an application catheter to the portal vein.

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.

Full Information

First Posted
July 16, 2008
Last Updated
February 5, 2016
Sponsor
Cytonet GmbH & Co. KG
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1. Study Identification

Unique Protocol Identification Number
NCT00718627
Brief Title
Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytonet GmbH & Co. KG

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urea Cycle Disorders, Carbamoylphosphate Synthetase I Deficiency, Ornithine Transcarbamylase Deficiency, Citrullinemia
Keywords
Urea cycle Disorders, Carbamoylphosphate synthetase I deficiency, Ornithine transcarbamoylase deficiency, Argininosuccinate synthase deficiency, Citrullinemia, newborns, infants, liver cell transplantation, liver cell infusion

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HHLivC Therapy Group
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Human Heterologous Liver Cells
Intervention Description
Multiple applications of liver cell suspension for infusion
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility 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 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Georg Hoffmann, Prof.
Organizational Affiliation
University Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Children's Hospital, Heinrich-Heine University
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
University Children's Hospital
City
Heidelberg
ZIP/Postal Code
D-69120
Country
Germany

12. IPD Sharing Statement

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

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