Citrulline for Children Undergoing Cardiopulmonary Bypass Surgery

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rick Barr, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00201214
First received: September 16, 2005
Last updated: September 10, 2013
Last verified: September 2013
  Purpose

This study will determine the pharmacokinetics and safety of intravenous citrulline given to children undergoing cardiopulmonary bypass for the correction of congenital heart defects.


Condition Intervention Phase
Cardiovascular Diseases
Heart Diseases
Heart Defects, Congenital
Drug: Citrulline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Clinical Trial to Determine the Pharmacokinetics and Safety Profile of Citrulline in Children Undergoing Cardiopulmonary Bypass

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Oxygen index (OI) data to assess increased PVT [ Time Frame: Measured through the use of continuous mean arterial pressure monitoring ] [ Designated as safety issue: No ]
  • Qp:Qs ratios to assess increased PVT [ Time Frame: Measured by blood gases collected 48 hours post-operative ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 26
Study Start Date: December 2003
Study Completion Date: December 2009
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Citrulline
    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.
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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00201214

Locations
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
Vanderbilt University
Investigators
Study Chair: Frederick E. Barr, MD, MSCI Vanderbilt University
  More Information

Publications:
Responsible Party: Rick Barr, Pediatric Critical Care Faculty, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00201214     History of Changes
Obsolete Identifiers: NCT00178815
Other Study ID Numbers: 281, R01HL073317, R01 HL73317
Study First Received: September 16, 2005
Last Updated: September 10, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Heart Defects, Congenital
Cardiovascular Abnormalities

ClinicalTrials.gov processed this record on October 01, 2014