Citrulline for Children Undergoing Cardiopulmonary Bypass Surgery

NCT ID: NCT00201214

Last Updated: 2013-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-12-31

Study Completion Date

2009-12-31

Brief Summary

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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

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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.

Conditions

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Cardiovascular Diseases Heart Diseases Heart Defects, Congenital

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Vanderbilt University

OTHER

Sponsor Role lead

Responsible Party

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Rick Barr

Pediatric Critical Care Faculty

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Frederick E. Barr, MD, MSCI

Role: STUDY_CHAIR

Vanderbilt University

Locations

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Vanderbilt University

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 17662768 (View on PubMed)

Other Identifiers

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R01HL073317

Identifier Type: NIH

Identifier Source: secondary_id

View Link

281

Identifier Type: -

Identifier Source: org_study_id

NCT00178815

Identifier Type: -

Identifier Source: nct_alias