NCT00718627

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2008

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2008

Completed
15 days until next milestone

First Submitted

Initial submission to the registry

July 16, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 18, 2008

Completed
7.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2015

Completed
Last Updated

February 8, 2016

Status Verified

February 1, 2016

Enrollment Period

7.3 years

First QC Date

July 16, 2008

Last Update Submit

February 5, 2016

Conditions

Urea Cycle DisordersCarbamoylphosphate Synthetase I DeficiencyOrnithine Transcarbamylase DeficiencyCitrullinemia

Keywords

Urea cycle DisordersCarbamoylphosphate synthetase I deficiencyOrnithine transcarbamoylase deficiencyArgininosuccinate synthase deficiencyCitrullinemianewbornsinfantsliver cell transplantationliver cell infusion

Outcome Measures

Primary Outcomes (1)

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

    7 - 15 weeks

Secondary Outcomes (1)

  • 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.

    7-15 weeks

Study Arms (1)

HHLivC Therapy Group

EXPERIMENTAL
Biological: Human Heterologous Liver Cells

Interventions

Human Heterologous Liver CellsBIOLOGICAL

Multiple applications of liver cell suspension for infusion

HHLivC Therapy Group

Eligibility Criteria

Age1 Day - 5 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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 \[Citrullinaemia\]
  • Accessibility of the portal vein
  • Plasma ammonia level ≤ 250 μmol/l
  • Written informed consent

You may not qualify if:

  • 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
  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University Children's Hospital, Heinrich-Heine University

Düsseldorf, 40225, Germany

Location

University Children's Hospital

Heidelberg, D-69120, Germany

Location

MeSH Terms

Conditions

Urea Cycle Disorders, InbornOrnithine Carbamoyltransferase Deficiency DiseaseCitrullinemia

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesAmino Acid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic DiseasesGenetic Diseases, X-Linked

Study Officials

  • Georg Hoffmann, Prof.

    University Children's Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 16, 2008

First Posted

July 18, 2008

Study Start

July 1, 2008

Primary Completion

November 1, 2015

Study Completion

November 1, 2015

Last Updated

February 8, 2016

Record last verified: 2016-02

Locations

DE(2)