Effect of Feedings on Caffeine in Premature Infants

Caffeine Clinical Trial

Official title:

Effect of Feedings on Caffeine Pharmacokinetics and Metabolism in Premature Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02293824
• Other study ID #: Pro00058253
• Status: Completed
• Phase: N/A
• First received: November 14, 2014
• Last updated: September 11, 2017
• Start date: December 2014
• Est. completion date: June 30, 2017

Study information

• Verified date: June 2017
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Almost all infants born <29 weeks gestational age develop apnea of prematurity and are treated with caffeine. Type of diet and disease states may be significant contributors of variability in caffeine metabolism and pharmacokinetics (PK) in this population. This prospective, observational, open-label, opportunistic PK study will compare the population PK of caffeine between infants fed formula and infants fed exclusively breast milk; compare the activities of caffeine metabolizing enzymes between infants fed formula and infants fed exclusively breast milk; and determine the effect of hypoxia, hypotension, and infection on caffeine PK and metabolism in premature infants.

Description:

This study will use a consecutive patient sampling approach. All eligible participants admitted at each site will be approached. Caffeine and feedings will be administered per standard of care. Manipulations of caffeine dosing or feeding regimens will not be a part of this protocol. To minimize the amount of blood sampling, the investigators will use a sparse sampling methodology. Urine will be collected for analysis of caffeine and caffeine metabolite concentrations. Caffeine pharmacokinetics will be described by population pharmacokinetic analysis. Urinary concentrations of caffeine and its metabolites will be used to calculate metabolic ratios as markers of enzyme activity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 30, 2017
• Est. primary completion date: June 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 15 Days

Eligibility

Inclusion Criteria:

• Written informed consent from parent(s) or legal guardian(s)

• <29 weeks birth gestational age

• Postnatal age =15 days

• Receiving caffeine (intravenous or oral) per standard of care for prevention or treatment of apnea of prematurity

Exclusion Criteria:

• Known major congenital or chromosomal anomaly

Related Conditions & MeSH terms

• Apnea of Prematurity
• Caffeine
• Premature Birth
• Premature Newborn

Intervention

Drug:
• Caffeine
Given per standard of care.

Locations

Country	Name	City	State
United States	North Carolina Children's Hospital	Chapel Hill	North Carolina
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

References & Publications (10)

Blake MJ, Abdel-Rahman SM, Pearce RE, Leeder JS, Kearns GL. Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants. Pediatr Res. 2006 Dec;60(6):717-23. Epub 2006 Oct 25. — View Citation

Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics. 2006 Jun;117(6):1979-87. — View Citation

Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu VK, Walsh M, Finer N, Martin RJ. A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr. 2010 Jul;157(1):69-73. doi: 10.1016/j.jpeds.2010.01.046. Epub 2010 Mar 20. — View Citation

Gal P. Caffeine Therapeutic Drug Monitoring Is Necessary and Cost-effective. J Pediatr Pharmacol Ther. 2007 Oct;12(4):212-5. doi: 10.5863/1551-6776-12.4.212. — View Citation

Hassoun PM, Yu FS, Cote CG, Zulueta JJ, Sawhney R, Skinner KA, Skinner HB, Parks DA, Lanzillo JJ. Upregulation of xanthine oxidase by lipopolysaccharide, interleukin-1, and hypoxia. Role in acute lung injury. Am J Respir Crit Care Med. 1998 Jul;158(1):299-305. — View Citation

Janvier A, Khairy M, Kokkotis A, Cormier C, Messmer D, Barrington KJ. Apnea is associated with neurodevelopmental impairment in very low birth weight infants. J Perinatol. 2004 Dec;24(12):763-8. — View Citation

Le Guennec JC, Billon B. Delay in caffeine elimination in breast-fed infants. Pediatrics. 1987 Feb;79(2):264-8. — View Citation

Supnet MC, David-Cu R, Walther FJ. Plasma xanthine oxidase activity and lipid hydroperoxide levels in preterm infants. Pediatr Res. 1994 Sep;36(3):283-7. — View Citation

Xu H, Rajesan R, Harper P, Kim RB, Lonnerdal B, Yang M, Uematsu S, Hutson J, Watson-MacDonell J, Ito S. Induction of cytochrome P450 1A by cow milk-based formula: a comparative study between human milk and formula. Br J Pharmacol. 2005 Sep;146(2):296-305. — View Citation

Zhao J, Gonzalez F, Mu D. Apnea of prematurity: from cause to treatment. Eur J Pediatr. 2011 Sep;170(9):1097-105. doi: 10.1007/s00431-011-1409-6. Epub 2011 Feb 8. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clearance (CL) of caffeine at steady state	Using population pharmacokinetic analyses	Study days 0, 15, 30, 45, and 60.
Secondary	Volume of distribution (V) of caffeine at steady state	Using population pharmacokinetic analyses	Study days 0, 15, 30, 45, and 60
Secondary	Caffeine metabolizing enzyme activity using urinary metabolic ratios	Activity levels of CYP1A2, xanthine oxidase, and N-acetyltransferase 2	Study days 0, 15, 30, 45, and 60
Secondary	Fold change in caffeine clearance due to hypoxia, hypotension, and infections	Effect of hypoxia, hypotension, and infections on caffeine clearance	Study days 0, 15, 30, 45, and 60

External Links

•   Bedford Laboratories. CAFCIT (caffeine citrate) injection, CAFCIT (caffeine citrate) solution. 2013.