OPRC Protocols

Northwestern University

Clinical Study

Title: Optimizing Medication Management for Mothers with Depression (OPTI-MOM)

Lead PI: Katherine Wisner, MD, MS

Objectives/Description: The purpose of this multicenter, prospective, opportunistic study is to develop guidelines to determine the optimal use of SSRI antidepressants (i.e., sertraline, fluoxetine, citalopram/escitalopram) in 200 pregnant women already taking SSRI antidepressants. The multi-faceted approach will include the evaluation of changes over time in biomarkers (e.g., plasma SSRI and metabolite concentrations), self-reported depression and anxiety symptoms, as well as related side effects. Pregnant women will be approached to participate in two optional studies: 1) assessment of metabolic phenotypes using a probe drug cocktail to evaluate the activities of enzymes involved in antidepressant metabolism (target n=100) and 2) assessment of neonatal SSRI discontinuation syndrome (target n=80). The study team will investigate the impact of genomic variability on inter-individual differences, with focus on genes involved in the metabolism, elimination and therapeutic efficacy and drug transporters to the central nervous system.

Significance: Major Depressive Disorder is one of the one of the most common medical complications of pregnancy, with 7.5% of women having the onset of an episode. The goal of this Obstetric-Fetal Pharmacology Research Center is to support an interdisciplinary team to develop guidelines for optimal treatment of pregnant women with SSRI antidepressants. The impact of genetic factors on individual differences antidepressant dose requirements, plasma concentrations, and adverse effects in the newborn will be evaluated.

Link: www.clinicaltrials.gov/ct2/show/NCT02519790

Pilot Study

Title: SSRI Neonatal Discontinuation Syndrome

Lead PI: Laura J. Rasmussen-Torvik, PhD

Objectives/Description: This project will determine the maternal-fetal plasma concentrations and pharmacogenetic characteristics associated with neonatal SSRI discontinuation syndrome. Maternal and fetal CYP and P-glycoprotein genotypes will be assessed for their relationship to SSRI drug concentrations and neonatal abstinence syndrome.

Basic/Translational Research Study

Title: Pharmacogenomics of SSRI Optimization

Lead PI: Alfred L. George, Jr, MD

Objectives/Description: The goals of this study are: to understand mechanisms of pregnancy related changes in drug response and disposition; to investigate the impact of genomic variability on inter- individual difference in SSRI dosing, plasma concentrations and phamacodynamics during pregnancy; and to focus on genes involved in the metabolism and elimination of SSRIs, drug transporters responsible for SSRI access to the central nervous system, and genes encoding critical SSRI targets involved in therapeutic efficacy.
University of Pittsburgh
Clinical Study

Title: Impact of Pregnancy on Buprenorphine Pharmacokinetics and Pharmacodynamics

Lead PI: Steve Caritis, MD

Objectives/Description: This is a multicenter PK and pharmacodynamic (PD) opportunistic evaluation of sublingual buprenorphine (BUP) in pregnant women already taking BUP for opioid addiction. The primary research questions are whether BUP and metabolite exposure (reflected as the dose-adjusted area under curve) differs during pregnancy and between pregnancy and the postpartum state. The goal of the study is to define the pharmacokinetics of BUP and determine if there is a better way to gauge dosing based on objective, physiological parameters of satiety. The study will also aim to determine which maternal, placental or fetal factors impact the risk of Neonatal Abstinence Syndrome (NAS) and will define neonatal exposure to BUP through breast milk. A total of 40 participants will be recruited to participate in the main protocol; ancillary studies are planned.

Significance: This center proposes to address a pressing need in Obstetric Pharmacology related to buprenorphine treatment of opioid-addicted women. Pregnancy commonly motivates these women to stop use of “street drugs” such as heroin so they seek assistance by coming to drug centers and being converted to either methadone or buprenorphine. These medications are also addicting but pregnancy outcomes are better with use of these medications than with use of street heroin or other opioid substances. The health care system commonly fails these women as the transition to methadone and buprenorphine is difficult, demeaning and at times does not satisfy their cravings. The failure rate with buprenorphine is 20% with most failures occurring during this transition period. Minimal data exists on dosing of buprenorphine in pregnancy and this may explain the high initial failure rate. This research will determine the pharmacokinetics of buprenorphine and determine if there is a better way to gauge dosing based on objective and physiological parameters of satiety. We will also determine which maternal, placental or fetal factors impact the risk of Neonatal Abstinence Syndrome.

Link: www.clinicaltrials.gov/ct2/show/NCT02863601

Pilot Study

Title: Safety and Feasibility of Vaginal Administration of 17- hydroxy Progesterone Caproate for Treatment of Preterm Delivery

Lead PI: Raman Venkataramanan, PhD

Objectives/Description: This pilot study will evaluate the safety and feasibility of short and long term intravaginal administration of 17-hydroxy progresterone caproate.

Basic/Translational Research Study

Title: Pharmacokinetics of Buprenorphine (BUP) in Pregnant Rats

Lead PI: Raman Venkataramanan, PhD

Objectives/Description: The goals of this study are: to evaluate the impact of pregnancy on hepatic metabolism, as measured by IV administration of BUP; to evaluate the impact of pregnancy on gut metabolism, as measured by PO administration of BUP; and to determine the degree of hepatobiliary disposition of BUP and its metabolites in pregnancy using isolated organ perfusion system.
University of Texas Medical Branch
Clinical Study

Title: Pravastatin for the Prevention of Preeclampsia in High-Risk Women: A Phase I Pilot Study

Lead PI: Maged Costantine, MD

Objectives/Description: The purpose of this multi-center, phase I, double-blinded, randomized controlled trial (RCT) is to evaluate the maternal-fetal safety and pharmacokinetic (PK) profiles of pravastatin (20 mg/day) when used in pregnant women at high-risk of developing preeclampsia. The goals of this research are: to determine the maternal-fetal safety profile of pravastatin during pregnancy; to determine whether early prophylactic (preventive) treatment with pravastatin in high-risk women reverses the angiogenic imbalance associated with PE; to determine how pravastatin is metabolized during pregnancy (compared to the postpartum period); and to determine how genetic variations effect how pravastatin works in pregnant women. Twenty high-risk pregnant women will be randomized into treatment or placebo group and followed through pregnancy and delivery. Post-delivery PK data will be collected as well as umbilical cord and placenta samples. An additional consent is requested to contact the child’s pediatrician at or around 5-years post-delivery age for medical record access to obtain growth data, major medical problems and neurodevelopmental milestones.

Significance: Preeclampsia (PE) affects 3% to 8% of pregnant women and remains a major cause of morbidity and mortality. With no effective therapy for PE, the only approach to prevent maternal morbidity is delivery. Due to the similarities between PE and cardiovascular disease, we and others have demonstrated the ability of pravastatin to reverse several pathophysiologic pathways and phenotypic features of PE.

Link: www.clinicaltrials.gov/ct2/show/NCT01717586

Pilot Study

Title: Transplacental transfer of doxorubicin nanoformulations

Lead PI: Erik Rytting, PhD

Objectives/Description: This pilot study will determine the transplacental transfer of existing (marketed) and emerging nanoparticle formulations containing doxorubicin.

Basic/Translational Research Study

Title: Role of placental transporters and metabolizing enzymes in bio-disposition of pravastatin

Lead PI: Tatiana Nanovskaya, DDS, PhD

Objectives/Description: The goal of the proposed investigation is to identify and determine the activity of trophoblast transporters and metabolic enzymes that are involved in the placental biodisposition of pravastatin and define the extent of fetal exposure to pravastatin.

Obstetric-Fetal Pharmacology Research Centers

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OPRC Protocols

OPRC Protocols

Northwestern University

University of Pittsburgh

University of Texas Medical Branch