Urea Cycle DisordersPhase 2NCT01195753
Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders
A Phase 2 study testing HHLivC in people with Urea Cycle Disorders, run by Cytonet GmbH & Co. KG at 5 sites in 2 countries.
Trial summary
Treatment with liver cell infusion for children with urea cycle disorders (UCD). Read more about this study
- Who is it for?
- Ages 1 day to 5 years
- Conditions the study is for
- Urea Cycle Disorders
- What is being tested?
- HHLivC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Dec 2010to Dec 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
- Age: birth up to 5 years of age
- Ornithine transcarbamylase deficiency [OTCD], Carbamyl phosphate synthetase I deficiency [CPSD], Argininosuccinate synthetase deficiency [ASSD, Citrullinaemia]
- Written Informed Consent
Who cannot join
- Weight ≤ 3.5 kg
- Presence of acute infection at the time of inclusion
- Severe chronic or systemic disease other than study indication
- Structural liver disease (eg, cirrhosis, portal hypertension)
- Required valproate therapy
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Children's Memorial Hospital
Chicago, Illinois, 60614
Yale University
New Haven, Connecticut, 06250
Stanford University
Palo Alto, California, 94304
University of California
San Diego, California, 92103
About this study
Official title: Open, Prospective, Historic-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Infusion of Liver Cell Suspension (HHLivC) in Children With Urea Cycle Disorders.
Treatment with liver cell infusion for children with urea cycle disorders (UCD).
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, young children with UCD 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
- Being tested
- HHLivC
- Keywords
- Urea cycle Disorders
- Medical subject headings
- Urea Cycle Disorders, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HHLivCBiological
multiple infusion of liver cells
| Study group | Role | What they receive |
|---|---|---|
| Liver Cell Infusion | Experimental | Not described Receives: Biological: HHLivC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in 13C urea formation from baseline to 2 and 4 months after first HHLivC infusion
Measured: Baseline to 2 and 4 months
Secondary outcomes (1)
Frequency and severity of metabolic crises
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2010 (estimated)
- Study startDec 2010
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytonet GmbH & Co. KG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01195753
- Sponsor's protocol ID
- CCD05
- Status last verified
- Feb 2016
- First submitted
- 2 Mar 2010
- Last updated
- 8 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Meyburg J, Das AM, Hoerster F, Lindner M, Kriegbaum H, Engelmann G, Schmidt J, Ott M, Pettenazzo A, Luecke T, Bertram H, Hoffmann GF, Burlina A. One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects. Transplantation. 2009 Mar 15;87(5):636-41. doi: 10.1097/TP.0b013e318199936a.
PubMed 19295306
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, Historic-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Infusion of Liver Cell Suspension (HHLivC) in Children With Urea Cycle Disorders.
- ClinicalTrials.gov ID
- NCT01195753
- Acronym / sponsor ID
- CCD05
- Conditions
- Urea Cycle Disorders
- Keywords
- Urea cycle Disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Cytonet GmbH & Co. KGIndustry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 6 Sep 2010 (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.
Treatment with liver cell infusion for children with urea cycle disorders (UCD).
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, young children with UCD 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 |
|---|---|---|
| Liver Cell Infusion | Experimental | Biological: HHLivC |
Who may qualify
- Ages
- 1 day to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Age: birth up to 5 years of age
- Ornithine transcarbamylase deficiency [OTCD], Carbamyl phosphate synthetase I deficiency [CPSD], Argininosuccinate synthetase deficiency [ASSD, Citrullinaemia]
- Written Informed Consent
Key exclusion criteria (5 listed)
- Weight ≤ 3.5 kg
- Presence of acute infection at the time of inclusion
- Severe chronic or systemic disease other than study indication
- Structural liver disease (eg, cirrhosis, portal hypertension)
- Required valproate therapy
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 |
|---|---|---|
| HHLivCmultiple infusion of liver cells | Biological | Liver Cell Infusion |
Primary outcome
Changes in 13C urea formation from baseline to 2 and 4 months after first HHLivC infusion
Time frame: Baseline to 2 and 4 months
1 secondary outcome
Frequency and severity of metabolic crises
Time frame: 6 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2016.
- Background: PubMed 19295306Meyburg J, Das AM, Hoerster F, Lindner M, Kriegbaum H, Engelmann G, Schmidt J, Ott M, Pettenazzo A, Luecke T, Bertram H, Hoffmann GF, Burlina A. One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects. Transplantation. 2009 Mar 15;87(5):636-41. doi: 10.1097/TP.0b013e318199936a.
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HHLivC in people with Urea Cycle Disorders, run by Cytonet GmbH & Co. KG at 5 sites in 2 countries.
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 3 inclusion and 5 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: stopped early, 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 5 sites in United States, Canada. 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 was stopped early. Results are not available in the source record.
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?
Changes in 13C urea formation from baseline to 2 and 4 months after first HHLivC infusion (time frame: Baseline to 2 and 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01195753, which also lists 1 linked publication.
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.