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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Bronchopulmonary Dysplasia

Intervention / Treatment
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* Drug: Intravenous L-Citrulline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Days
Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics and dose finding in preterm infants with BPD |  | Surrounding Dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchopulmonary Dysplasia, Prematurity, Lung Disease, preterm infants