Citrulline for Children Undergoing Cardiopulmonary Bypass Surgery

Phase 1

Completed

• Conditions: Cardiovascular Diseases; Heart Diseases; Heart Defects, Congenital

• Registration Number: NCT00201214
• Lead Sponsor: Vanderbilt University

Brief 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.

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 Timeline

• Study Start: 2003-12
• Study First Submitted: 2005-09-16
• Study First Submitted QC: 2005-09-16
• Study First Posted: 2005-09-20
• Primary Completion: 2006-01
• Study Completion: 2009-12
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-10
• Last Update Posted: 2013-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• Undergoing cardiopulmonary bypass via one of the following surgical procedures:

  1. AVSD repair
  2. VSD repair
  3. Bidirectional Glenn
  4. Modified Fontan
  5. Arterial Switch

• Parents willing and able to sign consent

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Oxygen index (OI) data to assess increased PVT	Measured through the use of continuous mean arterial pressure monitoring
Qp:Qs ratios to assess increased PVT	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 through the use of continuous mean arterial pressure monitoring 48 hours post-operative

Trial Locations

Locations (1)

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States