Urea Cycle DisordersPhase 2NCT00718627
Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders
A Phase 2 study testing Human Heterologous Liver Cells in people with Urea Cycle Disorders and Carbamoylphosphate Synthetase I Deficiency, run by Cytonet GmbH & Co. KG at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 5 years
- Conditions the study is for
- Urea Cycle Disorders, Carbamoylphosphate Synthetase I Deficiency, Ornithine Transcarbamylase Deficiency
- What is being tested?
- Human Heterologous Liver Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesGermany
- Study dates
- Jul 2008to Nov 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
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- Accessibility of the portal vein
- Plasma ammonia level ≤ 250 μmol/l
- Written informed consent
Who cannot join
- 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
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- 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)
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
University Children's Hospital, Heinrich-Heine University
Düsseldorf, 40225
University Children's Hospital
Heidelberg, D-69120
About this study
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)
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.
Read the 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.
- Conditions
- Urea Cycle Disorders, Carbamoylphosphate Synthetase I Deficiency, Ornithine Transcarbamylase Deficiency, Citrullinemia
- Being tested
- Human Heterologous Liver Cells
- Keywords
- Urea cycle Disorders, Carbamoylphosphate synthetase I deficiency, Ornithine transcarbamoylase deficiency, Argininosuccinate synthase deficiency, Citrullinemia, newborns, infants, liver cell transplantation, liver cell infusion
- Medical subject headings
- Urea Cycle Disorders, Inborn, Ornithine Carbamoyltransferase Deficiency Disease, Citrullinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Heterologous Liver CellsBiological
Multiple applications of liver cell suspension for infusion
| Study group | Role | What they receive |
|---|---|---|
| HHLivC Therapy Group | Experimental | Not described Receives: Biological: Human Heterologous Liver Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of the application of liver cells, safety of the placement of an application catheter to the portal vein.
Measured: 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.
Measured: 7-15 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urea Cycle DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytonet GmbH & Co. KG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Georg Hoffmann, Prof., Principal investigator, University Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00718627
- Sponsor's protocol ID
- CCD02
- Other IDs
- CCD02, 2006-000136-27
- Status last verified
- Feb 2016
- First submitted
- 16 Jul 2008
- Last updated
- 8 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00718627
- Acronym / sponsor ID
- CCD02
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Cytonet GmbH & Co. KGIndustry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 18 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HHLivC Therapy Group | Experimental | Biological: Human Heterologous Liver Cells |
Who may qualify
- Ages
- 1 day to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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:
- A DNA analysis will further confirm diagnosis prior to or after inclusion according to the protocol.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Human Heterologous Liver CellsMultiple applications of liver cell suspension for infusion | Biological | HHLivC Therapy Group |
Primary outcome
Safety of the application of liver cells, safety of the placement of an application catheter to the portal vein.
Time frame: 7 - 15 weeks
1 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.
Time frame: 7-15 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Georg Hoffmann, Prof. principal investigator
University Children's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Human Heterologous Liver Cells in people with Urea Cycle Disorders and Carbamoylphosphate Synthetase I Deficiency, run by Cytonet GmbH & Co. KG at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of the application of liver cells, safety of the placement of an application catheter to the portal vein. (time frame: 7 - 15 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2016.