Intravenous L-Citrulline to Treat Children Undergoing Heart Bypass Surgery : Revised Protocol
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | Any - 6 |
| Updated: | 1/25/2017 |
| Start Date: | September 2010 |
| End Date: | April 2012 |
Phase IB Double Blind, Randomized, Placebo Controlled Clinical Trial to Determine the Pharmacokinetics and Safety of a Revised Protocol of Intravenous L-Citrulline (Citrupress®) Versus Placebo in Children Undergoing Cardiopulmonary Bypass
This clinical trial will determine the safety and effectiveness of intravenous L-citrulline
in children undergoing cardiopulmonary bypass during heart surgery. Participants will be
randomly assigned to either L-citrulline or a placebo (a substance that has no medicine in
it).
Citrulline is a protein building block in the body that can convert into another substance,
nitric oxide (NO), which controls blood pressure in the lungs. Increased blood pressure in
the lungs can be an important surgical problem; it may also lead to problems following
surgery, such as severe high blood pressure in the lungs (pulmonary hypertension), increased
time spent on a breathing machine, and a longer stay in the intensive care unit (ICU). The
hypothesis of this study is that perioperative supplementation with intravenous citrulline
will increase plasma citrulline, arginine and NO metabolites and prevent elevations in the
postoperative PVT leading to a decrease in the duration of postoperative invasive mechanical
ventilation.
The objective of this study is to determine in a randomized placebo controlled phase IB
multicenter clinical trial if a revised protocol of intravenous L-citrulline delivery given
perioperatively achieves a plasma citrulline level of > 100 umol/L in children undergoing
surgical repair of an atrial septal defect,ventricular septal defect or an atrioventricular
septal defect.
in children undergoing cardiopulmonary bypass during heart surgery. Participants will be
randomly assigned to either L-citrulline or a placebo (a substance that has no medicine in
it).
Citrulline is a protein building block in the body that can convert into another substance,
nitric oxide (NO), which controls blood pressure in the lungs. Increased blood pressure in
the lungs can be an important surgical problem; it may also lead to problems following
surgery, such as severe high blood pressure in the lungs (pulmonary hypertension), increased
time spent on a breathing machine, and a longer stay in the intensive care unit (ICU). The
hypothesis of this study is that perioperative supplementation with intravenous citrulline
will increase plasma citrulline, arginine and NO metabolites and prevent elevations in the
postoperative PVT leading to a decrease in the duration of postoperative invasive mechanical
ventilation.
The objective of this study is to determine in a randomized placebo controlled phase IB
multicenter clinical trial if a revised protocol of intravenous L-citrulline delivery given
perioperatively achieves a plasma citrulline level of > 100 umol/L in children undergoing
surgical repair of an atrial septal defect,ventricular septal defect or an atrioventricular
septal defect.
Increased pulmonary vascular tone (PVT) can complicate the postoperative course of the
following five 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) bidirectional
Glenn shunt procedure; and 5) Fontan procedure for single ventricle lesions. PVT is
partially controlled by 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 six previous surgical procedures. It was found that urea cycle function and plasma
arginine levels were significantly decreased in all participants. Furthermore, participants
with increased PVT had significantly lower arginine levels compared to participants 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. It is 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.
following five 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) bidirectional
Glenn shunt procedure; and 5) Fontan procedure for single ventricle lesions. PVT is
partially controlled by 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 six previous surgical procedures. It was found that urea cycle function and plasma
arginine levels were significantly decreased in all participants. Furthermore, participants
with increased PVT had significantly lower arginine levels compared to participants 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. It is 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.
Inclusion Criteria:
1. Informed Consent signed by the subject's legal representative
2. Subjects < 6 years old
3. Subjects undergoing cardiopulmonary bypass for repair of an atrial septal defect, a
ventricular septal defect or an atrioventricular septal defect
Exclusion Criteria:
1. Pulmonary artery or vein abnormalities being addressed surgically
2. Preoperative requirement for invasive mechanical ventilation or intravenous inotrope
support
3. Any condition which, in the opinion of the investigator, might interfere with study
objectives
We found this trial at
2
sites
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
Cincinnati, Ohio 45229
1-513-636-4200
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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