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

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)

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 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.

Condition

Urea Cycle Disorders

Intervention

Human Heterologous Liver Cells

Study Arms / Comparison Groups

 HHLivC Therapy Group
Description:  

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

Biological

Estimated Enrollment

12

Start Date

July 2008

Completion Date

November 2015

Primary Completion Date

November 2015

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)
      

Gender

All

Ages

N/A - 5 Years

Accepts Healthy Volunteers

No

Contacts

Georg Hoffmann, Prof., , 

Location Countries

Germany

Location Countries

Germany

Administrative Informations


NCT ID

NCT00718627

Organization ID

CCD02

Secondary IDs

CCD02

Responsible Party

Sponsor

Study Sponsor

Cytonet GmbH & Co. KG


Study Sponsor

Georg Hoffmann, Prof., Principal Investigator, University Children's Hospital


Verification Date

February 2016