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

Vanderbilt University

Status and phase: Withdrawn; Phase 1

Conditions: Bronchopulmonary Dysplasia

Treatments: Drug: Intravenous L-Citrulline

Study type: Interventional

Funder types: Other

Identifiers

NCT00742534

BPD2008

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 2 to 14 days old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)