Phase 1 Intravenous Citrulline for the Prevention of Bronchopulmonary Dysplasia in Preterm Infants
Summary
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.
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.
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Bronchopulmonary Dysplasia
Intervention
Intravenous L-Citrulline
Location
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville
Tennessee
United States
37232
Status
Not yet recruiting
Source
Vanderbilt University
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00742534
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Ornithine Carbamoyltransferase
A urea cycle enzyme that catalyzes the formation of orthophosphate and L-citrulline (CITRULLINE) from CARBAMOYL PHOSPHATE and L-ornithine (ORNITHINE). Deficiency of this enzyme may be transmitted as an X-linked trait. EC 2.1.3.3.
Bronchopulmonary Dysplasia
A chronic lung disease developed after OXYGEN INHALATION THERAPY or mechanical ventilation (VENTILATION, MECHANICAL) usually occurring in certain premature infants (INFANT, PREMATURE) or newborn infants with respiratory distress syndrome (RESPIRATORY DISTRESS SYNDROME, NEWBORN). Histologically, it is characterized by the unusual abnormalities of the bronchioles, such as METAPLASIA, decrease in alveolar number, and formation of CYSTS.
Fibrous Dysplasia Of Bone
A disease of bone marked by thinning of the cortex and replacement of bone marrow by gritty fibrous tissue containing bony spicules, producing pain, disability, and gradually increasing deformity. Only one bone may be involved (FIBROUS DYSPLASIA, MONOSTOTIC) or several (FIBROUS DYSPLASIA, POLYOSTOTIC). (From Dorland, 28th ed)
Septo-optic Dysplasia
A condition resulting from congenital malformations involving the brain. The syndrome of septo-optic dysplasia combines hypoplasia or agenesis of the SEPTUM PELLUCIDUM and the OPTIC NERVE. The extent of the abnormalities can vary. Septo-optic dysplasia is often associated with abnormalities of the hypothalamic and other diencephalic structures, and HYPOPITUITARISM.
Vitamin E Deficiency
A nutritional condition produced by a deficiency of VITAMIN E in the diet, characterized by posterior column and spinocerebellar tract abnormalities, areflexia, ophthalmoplegia, and disturbances of gait, proprioception, and vibration. In premature infants vitamin E deficiency is associated with hemolytic anemia, thrombocytosis, edema, intraventricular hemorrhage, and increasing risk of retrolental fibroplasia and bronchopulmonary dysplasia. An apparent inborn error of vitamin E metabolism, named familial isolated vitamin E deficiency, has recently been identified. (Cecil Textbook of Medicine, 19th ed, p1181)
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PubMed Articles
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The purpose of this revised statement is to review current information on the use of postnatal glucocorticoids to prevent or treat bronchopulmonary dysplasia in the preterm infant and to make updated...
Bronchopulmonary dysplasia (BPD) is characterized by arrested alveolar development and complicated by pulmonary hypertension (PH). Nitric oxide (NO) promotes alveolar growth. Inhaled NO (iNO) ameliora...
Neonatal Brucellosis and Breast Milk.
In this case report the authors present an extremely low birth weight premature infant with neonatal brucellosis whose mother had been treated for brucellosis during pregnancy. Infant developed mild r...
BACKGROUND: In animal models, inhaled nitric oxide improved gas exchange and lung structural development, but its use in premature infants at risk of developing bronchopulmonary dysplasia remains cont...
Exhaled air temperature in children with bronchopulmonary dysplasia.
BACKGROUND: Because they have similar functional and clinical profiles, bronchopulmonary dysplasia (BPD) survivors are often treated as asthmatic patients. In truth, very little is known about the pos...
