Cardiovascular DiseasesPhase 1/2NCT00201214
Citrulline for Children Undergoing Cardiopulmonary Bypass Surgery
A Phase 1/2 study testing Citrulline in people with Cardiovascular Diseases and Heart Diseases, run by Vanderbilt University at 1 site in United States.
Trial summary
This study will determine the pharmacokinetics and safety of intravenous citrulline given to children undergoing cardiopulmonary bypass for the correction of congenital heart defects. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Cardiovascular Diseases, Heart Diseases, Heart Defects, Congenital
- What is being tested?
- Citrulline
- Type of treatment
- Injection or infusion
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2003to Dec 2009
- Phase
- Phase 1/2
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Undergoing cardiopulmonary bypass via one of the following surgical procedures:
- AVSD repair
- VSD repair
- Bidirectional Glenn
- Modified Fontan
- Arterial Switch
- Parents willing and able to sign consent
Who cannot join
- Pulmonary artery or vein abnormalities not being addressed surgically
- Preoperative requirement for mechanical ventilation or intravenous inotrope support
- Any condition that might interfere with study objectives
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Clinical Trial to Determine the Pharmacokinetics and Safety Profile of Citrulline in Children Undergoing Cardiopulmonary Bypass
This study will determine the pharmacokinetics and safety of intravenous citrulline given to children undergoing cardiopulmonary bypass for the correction of congenital heart defects.
Read the detailed description
BACKGROUND:
Increased pulmonary vascular tone (PVT) can complicate the postoperative course of the following six surgical procedures for congenital heart defects: 1) unrestrictive ventricular septal defect (VSD) repair; 2) atrioventricular septal (AVSD) repair; 3) arterial switch procedure for transposition of the great arteries (TGA); 4) Norwood I procedure; 5) bidirectional Glenn shunt procedure; and 6) Fontan procedure for single ventricle lesions. PVT is partially controlled by nitric oxide (NO). Arginine, the precursor to NO, is a product of the urea cycle. Preliminary data have been presented regarding 169 infants and children who have undergone one of the six previous surgical procedures. It was found that urea cycle function and plasma arginine levels were significantly decreased in all patients. Furthermore, patients with increased PVT had significantly lower arginine levels compared to patients with normal PVT. Finally, a genetic single nucleotide polymorphism (SNP) in the rate limiting urea cycle enzyme (carbamyl phosphate synthetase I [CPSl T1405N]) appeared to affect postoperative plasma arginine levels and PVT. The hypothesis is that genetic polymorphisms in the rate limiting urea cycle enzyme CPSl, and other important enzymes in the urea cycle, influence the availability of NO precursors. It is further hypothesized that perioperative enhancement of urea cycle function with the key urea cycle intermediate (citrulline) will increase plasma arginine and NO metabolites, and prevent elevations in PVT.
DESIGN NARRATIVE:
This phase I/II study will determine the pharmacokinetics and safety of three doses of intravenous citrulline that will be given to children undergoing cardiopulmonary bypass for the correction of congenital heart defects.
- Being tested
- Citrulline
- Medical subject headings
- Cardiovascular Diseases, Heart Diseases, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CitrullineDrug
Phase I - 150mg/kg IV bolus after initiation of cardiopulmonary bypass with dosage escalation study 50mg/kg, 100mg/kg, 150mg/kg IV at 6, 12, 24, 48 hours post operative. Phase II - 150mg/kg IV bolus after initiation of cardiopulmonary bypass with 9mg/kg/hr continuous IV starting 4 hours post bolus and infusing for 48 hours or discharge from PCCU.
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxygen index (OI) data to assess increased PVT
Measured: Measured through the use of continuous mean arterial pressure monitoring
Qp:Qs ratios to assess increased PVT
Measured: Measured by blood gases collected 48 hours post-operative
Increased PVT as measured by a sustained mean pulmonary artery pressure greater than 20 mm Hg for at least 2 hours during the first 24 hours postoperatively
Measured: Measured through the use of continuous mean arterial pressure monitoring 48 hours post-operative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startDec 2003
- Primary completionJan 2006
- Study completionDec 2009
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 Cardiovascular DiseasesStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Rick Barr, Vanderbilt University
- Investigators
- Frederick E. Barr, MD, MSCI, Study chair, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00201214
- Sponsor's protocol ID
- 281
- Other IDs
- R01HL073317
- Status last verified
- Sep 2013
- First submitted
- 16 Sep 2005
- Last updated
- 12 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26. doi: 10.1016/j.jtcvs.2007.02.043.
PubMed 17662768
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Trial to Determine the Pharmacokinetics and Safety Profile of Citrulline in Children Undergoing Cardiopulmonary Bypass
- ClinicalTrials.gov ID
- NCT00201214
- Acronym / sponsor ID
- 281
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Dec 2003
- Primary completion
- Jan 2006 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 20 Sep 2005 (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.
This study will determine the pharmacokinetics and safety of intravenous citrulline given to children undergoing cardiopulmonary bypass for the correction of congenital heart defects.
Detailed description
BACKGROUND:
Increased pulmonary vascular tone (PVT) can complicate the postoperative course of the following six surgical procedures for congenital heart defects: 1) unrestrictive ventricular septal defect (VSD) repair; 2) atrioventricular septal (AVSD) repair; 3) arterial switch procedure for transposition of the great arteries (TGA); 4) Norwood I procedure; 5) bidirectional Glenn shunt procedure; and 6) Fontan procedure for single ventricle lesions. PVT is partially controlled by nitric oxide (NO). Arginine, the precursor to NO, is a product of the urea cycle. Preliminary data have been presented regarding 169 infants and children who have undergone one of the six previous surgical procedures. It was found that urea cycle function and plasma arginine levels were significantly decreased in all patients. Furthermore, patients with increased PVT had significantly lower arginine levels compared to patients with normal PVT. Finally, a genetic single nucleotide polymorphism (SNP) in the rate limiting urea cycle enzyme (carbamyl phosphate synthetase I [CPSl T1405N]) appeared to affect postoperative plasma arginine levels and PVT. The hypothesis is that genetic polymorphisms in the rate limiting urea cycle enzyme CPSl, and other important enzymes in the urea cycle, influence the availability of NO precursors. It is further hypothesized that perioperative enhancement of urea cycle function with the key urea cycle intermediate (citrulline) will increase plasma arginine and NO metabolites, and prevent elevations in PVT.
DESIGN NARRATIVE:
This phase I/II study will determine the pharmacokinetics and safety of three doses of intravenous citrulline that will be given to children undergoing cardiopulmonary bypass for the correction of congenital heart defects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Undergoing cardiopulmonary bypass via one of the following surgical procedures:
- Parents willing and able to sign consent
Key exclusion criteria (3 listed)
- Pulmonary artery or vein abnormalities not being addressed surgically
- Preoperative requirement for mechanical ventilation or intravenous inotrope support
- Any condition that might interfere with study objectives
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 |
|---|---|---|
| CitrullinePhase I - 150mg/kg IV bolus after initiation of cardiopulmonary bypass with dosage escalation study 50mg/kg, 100mg/kg, 150mg/kg IV at 6, 12, 24, 48 hours post operative. Phase II - 150mg/kg IV bolus after initiation of cardiopulmonary bypass with 9mg/kg/hr continuous IV starting 4 hours post bolus and infusing for 48 hours or discharge from PCCU. | Drug | – |
Primary outcome
Oxygen index (OI) data to assess increased PVT
Time frame: Measured through the use of continuous mean arterial pressure monitoring
Qp:Qs ratios to assess increased PVT
Time frame: Measured by blood gases collected 48 hours post-operative
Increased PVT as measured by a sustained mean pulmonary artery pressure greater than 20 mm Hg for at least 2 hours during the first 24 hours postoperatively
Time frame: Measured through the use of continuous mean arterial pressure monitoring 48 hours post-operative
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 12 Sep 2013.
- Results publication: PubMed 17662768Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26. doi: 10.1016/j.jtcvs.2007.02.043.
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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.
Frederick E. Barr, MD, MSCI study chair
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Citrulline in people with Cardiovascular Diseases and Heart Diseases, run by Vanderbilt University at 1 site in United States.
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 7 inclusion and 3 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 12 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Oxygen index (OI) data to assess increased PVT (time frame: Measured through the use of continuous mean arterial pressure monitoring). The study lists 3 primary outcomes in all. 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 NCT00201214, 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 12 Sep 2013.