Apnea of Prematurity, Bronchopulmonary Dysplasia, Premature Birth, Preterm Labor With Preterm Delivery, Respiratory Distress Syndrome
Conditions
Keywords
caffeine, preterm labor, prematurity, pharmacokinetics, bronchopulmonary dysplasia, apnea of prematurity
Brief summary
The goal of this study is to learn how a pregnant person's body processes caffeine and how much caffeine crosses the placenta to the baby. A small dose of caffeine will be given to each pregnant participant before delivery. Blood will be drawn to measure caffeine levels in the pregnant mother. Blood will also be taken from the placenta and from the newborn to measure caffeine levels. This data will be used to form a computer model of the metabolism of caffeine during pregnancy.
Interventions
DRUGCaffeine citrate
A single dose of 100 mg of caffeine citrate will be given to each pregnant participant.
Sponsors
Indiana University
Indiana Clinical and Translational Sciences Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This study will include a single intervention group, divided into 3 cohorts across the range of gestational ages of interest.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pregnant women with risk of preterm delivery at 23 - 31+6 weeks with singleton gestation who are inpatient without a plan for discharge before delivery. 2. Informed consent provided for participation. 3. Cesarean delivery.
Exclusion criteria
1. Known major fetal congenital anomalies or genetic disorders. 2. Plan in place for limited neonatal resuscitation or comfort care only. 3. Preterm, premature rupture of membranes prior to 22 weeks gestation with concern for pulmonary hypoplasia. 4. Pre-eclampsia, gestational hypertension, or other gestational hypertensive disorder. 5. Fetal arrhythmia. 6. Seizure disorder. 7. Oligohydramnios due to renal anomalies or renal impairment. 8. Current or anticipated use of products that include sodium benzoate. 9. Maternal age \<18 years. 10. Maternal medical conditions in which caffeine or other stimulants would be contraindicated. 11. High likelihood of receiving terbutaline. 12. Use of the following medications, which may affect caffeine metabolism: fluvoxamine, ciprofloxacin, methoxsalen, mexiletine, vemurafenib, phenytoin, rifampin, and teriflunomide. 13. Significant acute or chronic medical, neurologic, or illness in the patient that, in the judgment of the Principal Investigator, could compromise subject safety, limit the ability to complete the study, and/or compromise the objectives of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of caffeine in pregnancy | 3 hours | Caffeine and primary metabolite concentrations will be determined in maternal plasma samples. Caffeine, paraxanthine, theophylline, and theobromine will be analyzed by HPLC-MS/MS (Sciex 6500) by the Indiana University Simon Comprehensive Cancer Center (IUSCCC)Clinical Pharmacology Analytical Core Laboratory. Pharmacokinetic modeling will be supported by the Indiana Clinical and Translational Sciences Institute Pharmacometric Modeling and Simulation Program. This model will be utilized to predict the maternal dose of caffeine required to achieve therapeutic concentrations in the neonate at the time of delivery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Placental transfer of caffeine | 1 hour | Caffeine and primary metabolite concentrations will be determined from cord blood samples. Caffeine, paraxanthine, theophylline, and theobromine will be analyzed by HPLC-MS/MS (Sciex 6500) by the Indiana University Simon Comprehensive Cancer Center (IUSCCC) Clinical Pharmacology Analytical Core Laboratory. Maternal: cord ratios for caffeine and metabolites will be determined for each gestational age range to assess transplacental uptake and compared to predicted maternal: cord ratios determined using physiologically based pharmacokinetic (PBPK) models. |
Countries
United States
Contacts
CONTACTAnna E Thomas, MD
PRINCIPAL_INVESTIGATORAnna Thomas, MD
Indiana University, Riley Hospital for Children
Outcome results
None listed