Phase 1 Intravenous Citrulline for the Prevention of Bronchopulmonary Dysplasia in Preterm Infants

This study has been withdrawn prior to enrollment.
(Study never began)
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00742534
First received: August 25, 2008
Last updated: December 27, 2011
Last verified: December 2011
  Purpose

Premature infants are at risk for developing bronchopulmonary dysplasia (BPD). L-citrulline may decrease that risk, but we do not know the safety or dose of this drug for use in premature babies. The purpose of this study is to determine the safety and optimal dose of intravenous L-citrulline in premature infants.


Condition Intervention Phase
Bronchopulmonary Dysplasia
Drug: Intravenous L-Citrulline
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Intravenous Citrulline for the Prevention of Bronchopulmonary Dysplasia in Preterm Infants

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Pharmacokinetics and dose finding in preterm infants with BPD [ Time Frame: Surrounding Dose ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: August 2008
Estimated Study Completion Date: August 2009
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Intravenous L-Citrulline
    This is a classic dose escalation using initial doses of 10 mg/kg of intravenous citrulline and advancing the dose by 10 mg/kg every 3 patients for a target peak plasma citrulline concentration of 100 umol/L. This regimen will be adjusted with pharmacokinetic data as it becomes available so that it may be adjusted to maintain appropriate serum levels of the urea cycle precursors and NO metabolites of interest.
Detailed Description:

This is a prospective phase I study of the safety, pharmacokinetics, and optimal dose of intravenously administered L-citrulline in premature infants born at 24 to 29 weeks estimated gestational age (EGA) and who are at risk for bronchopulmonary dysplasia (BPD). This is a classic dose escalation using initial doses of 10 mg/kg of intravenous citrulline and advancing the dose by 10 mg/kg every 3 patients for a target peak plasma citrulline concentration of 100 umol/L. These infants will undergo intense hemodynamic monitoring and have intermittent blood sampling to determine levels of amino acids and nitric oxide metabolites. From this, we will determine citrulline pharmacokinetics including half life, clearance, and volume of distribution. Intravenous L-citrulline will be provided by Asklepion Pharmaceuticals and mixed by the Investigational Drug Service of the Vanderbilt Hospital Clinical Pharmacy. The study will be monitored closely by a data safety monitoring board (DSMB) consisting of clinicians not involved with this study.

  Eligibility

Ages Eligible for Study:   up to 14 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 24-29 Weeks Gestation
  • Respiratory Distress requiring intubation and mechanical ventilation or positive pressure oxygen at 24 hours of life
  • Parents willing and able to sign consent

Exclusion Criteria:

  • Congenital malformation
  • Suspected genetic or metabolic syndrome
  • Surgical condition
  • Life expectancy < 24 hours
  • Pre-existing, sustained hypotension
  • Birth weight < 500 grams
  • Any condition which, in the opinion of the investigator, will interfere with the 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: NCT00742534

Locations
United States, Tennessee
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Frederick E Barr, MD, MSCI Vanderbilt University
  More Information

No publications provided

Responsible Party: Frederick E. Barr, MD, MSCI, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT00742534     History of Changes
Other Study ID Numbers: BPD2008
Study First Received: August 25, 2008
Last Updated: December 27, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
Bronchopulmonary Dysplasia
Prematurity
Lung Disease
preterm infants

Additional relevant MeSH terms:
Bronchopulmonary Dysplasia
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on August 21, 2014