Clinical Research Directory

Resources, Inspiration, Support and Empowerment (RISE) for Black Pregnant Women

Perinatal Mood and Anxiety Disorders (PMADs) encompass a range of mental health disorders that occur during pregnancy and up to one year postpartum. Approximately 13% of women experience PMADs. This rate doubles for those with adverse perinatal outcomes (APO) and triples in Black women. Recent research points to racism as one significant source of these health disparities. Cultural adaptations to improve communication with providers decrease rates of depression in minority patients as well as improve adherence to treatment, insight and alliance. Discrimination stress and worries about experiencing medical consequences are thought to increase systemic inflammation, a mechanism known to drive mental and physical symptoms. Inflammation has been implicated in both PMADs and APO, suggesting a shared underlying etiology. Evidence from our work suggests that inflammation contributes to the pathophysiology of PMADs. The proposed pilot randomized control trial will allow the investigators to build on promising preliminary results and identify whether our culturally relevant mobile Health (mHealth) intervention is effective in improving outcomes among Black pregnant women randomized to the intervention compared to a control group. The culturally relevant modules include building communication and self-advocacy skills and provide a support network. The primary objective of this research is to provide guidance for clinical care of Black women during the perinatal period, with the goal to improve mental health and physical health outcomes. A secondary goal is to examine novel inflammatory signatures that change as a function of the intervention to reduce PMADs in this population. As inflammation may be diagnostic of PMADs, identification of its role may shed light of potential intervention targets and provide critical knowledge to improve women's long-term health. PMAD symptoms will be assessed prospectively in 150 Black pregnant women, half of whom will be randomized to receive the culturally relevant mHealth intervention. The investigators hypothesize that women in the intervention group will have reduced rates of PMADs and APOs, an increase in adherence to mental health treatment and will report increased self-advocacy skills, increased communication with providers, and reduced levels of discrimination related stress. Participants will also have improved biological risk indicators including lower circulating C-reactive protein and a transcription profile of differentially expressed inflammatory genes, marked by a decreased activity of inflammatory transcription factors from blood spots. Given the high burden of both PMADs and APOs among Black mothers and the numerous consequences on maternal and child outcomes, it is imperative that investigators develop and implement effective interventions, and test the biological mechanisms that might drive these effects. This work is interdisciplinary, building on a network of community advocates to implement a novel mHealth intervention informed by real world experiences designed to enhance self-advocacy, reduce stress and prevent adverse outcomes

Early Detection of Gestational Diabetes Mellitus in Pregnancy

The purpose of this study is to develop an implementation protocol and test the feasibility and acceptability of a first trimester screening protocol for the early detection of gestational diabetes mellitus (GDM).

Permissive Versus Strict Intrapartum Glucose Management in Type 1 Diabetes (PRISM-T1D)

PRISM-TID is a single center non-inferiority randomized controlled trial of permissive intrapartum glucose management (intervention) versus strict intrapartum glucose management (standard of care) among pregnant individuals with type 1 diabetes (T1D) using hybrid closed loop therapy (HCL) who are admitted for labor management. Participants will be randomized in a 1:1 fashion to one of two intrapartum glycemic control options: permissive (70-140 mg/dL) or strict (70-110 mg/dL). The primary aim of this trial it to demonstrate that permissive intrapartum glucose management is not associated with an increased risk of neonatal dysglycemia compared with strict intrapartum glucose management.

Glycemic Control After Antenatal Corticosteroids in Women With Pregestational and Gestational Diabetes

There is a fundamental gap in understanding the maternal and neonatal effects of antenatal corticosteroid (ACS) administration in women with threatened preterm birth (PTB) who have diabetes. Since the initial discovery of ACS for neonatal benefit in 1972, more than 40 randomized controlled trials have been performed evaluating its efficacy. However, none of these trials have included women with T2DM, and there is limited data among women with gestational diabetes. While ACS have been shown to reduce neonatal morbidity associated with PTB in non-diabetic women, the side effects of ACS (maternal hyperglycemia and fetal hyperinsulinemia) may mitigate the neonatal benefit of ACS in women with diabetes. Before neonatal benefit of ACS can be evaluated in this population, the first step is to optimize maternal glycemic control after ACS. Previous studies evaluating maternal hyperglycemia after ACS have been limited by small sample size, retrospective study design, or insufficient glucose data. Use of continuous glucose monitoring (CGM) in a randomized clinical trial provides a unique opportunity to overcome these challenges. Our long-term goal is to improve maternal and child health among women with diabetes as an independently funded clinical researcher. The research objectives of this proposal are to test the efficacy of three treatment strategies at achieving maternal glycemic control after ACS and evaluate the association between maternal glycemic control and neonatal outcomes. Our central hypothesis is that treatment with a continuous insulin infusion will improve maternal glycemic control, which is key to improving neonatal outcomes, but at the cost of less patient satisfaction and more health resource utilization. This hypothesis will be tested by pursuing the following specific aims: 1) Test the efficacy of three treatment strategies (addition of sliding scale insulin, up-titration of home insulin, and continuous insulin infusion) at achieving maternal glycemic control after ACS and 2) Quantify the association between maternal glycemic control after ACS and neonatal morbidity. Completion of these aims will determine the optimal strategy to achieve maternal glycemic control after ACS and inform a larger, multicenter trial to improve neonatal outcomes among women with diabetes and threatened PTB.

Improvement of PPROM Management With Prophylactic Antimicrobial Therapy (iPROMPT)

To conduct an unblinded pragmatic randomized controlled trial (pRCT) "Improvement of PPROM Management with Prophylactic Antimicrobial Therapy (iPROMPT)" of a seven-day course of ceftriaxone, clarithromycin, and metronidazole versus the current standard of care of a seven-day course of ampicillin/amoxicillin and azithromycin or erythromycin to prolong pregnancy and decrease adverse perinatal outcomes among hospitalized pregnant individuals undergoing expectant management of PPROM \<34 weeks.

DECIDE: A Comparative Effectiveness Trial of Metformin Versus Insulin for the Treatment of Gestational Diabetes

This is a non-inferiority patient-centered and pragmatic comparative-effectiveness pregnancy randomized controlled trial (RCT) with postpartum maternal and child follow-up through 2 years of 1,572 individuals with gestational diabetes mellitus (GDM) randomized to oral metformin versus injectable insulin. This study will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. A total of 1,572 pregnant individuals with GDM who need pharmacotherapy will be recruited at 20 U.S. sites using consistent treatment criteria to metformin versus insulin. Participants and their children will be followed through delivery to two years postpartum.

Psychobiological Interventions in Pregnancy

This randomized control trial will evaluate whether a physical activity intervention can improve mental health and biologic markers of stress in pregnant people with depressive or anxiety symptoms. The study will enroll participants if they are presenting for prenatal care at Stanford Children's Health Obstetrics Clinic with a singleton gestation.

A Randomized Controlled Trial of Diabetes Screening Immediately Postpartum (DIP) and Follow Up PP CARE

DIP : To conduct a pragmatic, non-blinded randomized controlled trial (pRCT) of immediate in-patient postpartum OGTT prior to delivery discharge (intervention) versus 4-12 week outpatient postpartum OGTT (current standard care) to improve the frequency of post-partum diabetes screening among individuals with a pregnancy complicated by GDM. Follow up PP CARE: To engage with individuals with a history of GDM through a patient-centered mixed-methods survey and qualitative assessment to evaluate the barriers to and facilitators of Cardiovascular health (CVH) counseling and risk-reduction postpartum at the patient and healthcare system levels inclusive of Social determinants of health (SDOH) and structural factors, as well as patient preferences and perspectives on CVH and wellness interventions

Anticoagulation Profile in Pregnant Women Treated With Three Times a Day of Low Molecular Weight Heparin (LMWH)

Pregnancy is associated with a increased risk of developing blood clots. There is nearly a 5 times greater risk of developing a blood clot in pregnancy. Lovenox is a medication that helps to prevent the body from developing clots. It is safe to use in pregnancy. Previous studies have demonstrated that despite recommendation of Lovenox, to prevent blood clots, the majority of patient's (70 to 90%) did not receive adequate levels of Lovenox at times throughout the day, which likely increases the risk of developing clots. The increase in blood volume and increase in kidney function that occurs in pregnancy may contribute to the inadequate levels. Currently the recommendation for pregnant and nonpregnant patients requiring Lovenox, is to calculate the daily dose of Lovenox and split the dose, giving half in the morning and the other half in the evening. This research study proposes that due to changes in the body during pregnancy that the daily Lovenox dosing be split into three times a day to achieve more consistent levels of Lovenox than twice a day in pregnant women.

Transdermal Patch for BupRenorphine Induction DurinG PrEgnancy (Patch BRIDGE)

The goal of this clinical trial is to compare buprenorphine patch for induction (starting) of buprenorphine in pregnant patients with opioid use disorder. The main questions it aims to answer are: 1. Is there a buprenorphine induction method that results in the least moderate-to-severe opioid withdrawal symptoms in pregnant patients with opioid use disorder? 2. Is there a buprenorphine induction method that results in a higher treatment success rate? Under normal circumstances, patients who are planning to start sublingual (under the tongue) buprenorphine for opioid use disorder must first go into withdrawal to start the medication safely. Study participants will be given a buprenorphine patch during the required withdrawal period before starting sublingual treatment, and be surveyed daily by phone to assess their withdrawal symptoms. They will also be followed at prenatal appointments to evaluate treatment success based on urine drug screen results. Researchers will compare patients receiving no buprenorphine patch according to the current standard care protocol.

Relationship of DV Doppler Parameters to Perinatal Outcomes in IUGR vs Non-IUGR

This observational study investigates whether blood flow in the ductus venosus, a small fetal vein measured by Doppler ultrasound, is related to pregnancy outcomes. A total of pregnant women with and without intrauterine growth restriction (IUGR) will be examined between 24 and 37 weeks of gestation. Ductus venosus Doppler parameters will be recorded and compared with perinatal outcomes such as Apgar scores, neonatal intensive care unit admission, and perinatal mortality. The aim of this research is to improve the early identification of high-risk pregnancies and to support better monitoring and management strategies for fetal health.

Continuous Glucose Monitor Use in Pregnancy

The purpose of this study is to perform a randomized controlled trial among 180 pregnant women with type 2 diabetes mellitus (T2DM) comparing continuous glucose monitor (CGM) use to the standard of care of multiple daily fingerstick glucose monitoring and its impact on large for gestational age infants, maternal glycemic control, patient satisfaction, and additional adverse perinatal outcomes.

Relugolix Pregnancy Registry: An Observational Study of the Safety of Relugolix-Containing Therapy Exposure in Pregnant Women and Their Offspring

The Relugolix Pregnancy Registry is a prospective, observational cohort study designed to evaluate the association between relugolix-containing therapy exposure during pregnancy and subsequent maternal, fetal, and infant outcomes. Data will be collected from enrolled pregnant women and the healthcare providers (HCPs) involved in their care or the care of their infants, if applicable.

Intensive Glycemic Targets in Overweight and Obese Women With Gestational Diabetes

This is a multicenter randomized clinical trial of 828 overweight and obese individuals with gestational diabetes designed to compare standard to intensive glycemic targets.

MYFEMBREE®: A Retrospective Cohort Study Using an Administrative Healthcare Database to Assess Pregnancy Outcomes in Women Treated With Relugolix Combination Therapy

This is a retrospective cohort study that will be conducted using secondary de-identified electronic healthcare data (EHD) that originally were collected for the purposes of health insurance billing and/or routine patient care from healthcare providers (HCPs). The study is designed to evaluate the association between relugolix combination therapy (relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) exposure during pregnancy and subsequent fetal and infant outcomes.

PRISMA Maternal and Newborn Health Study

Access to quality antenatal care (ANC) and postnatal care (PNC), including maternal, newborn, and infant services, is integral to reducing adverse pregnancy-related health outcomes and promoting positive birth experiences. The World Health Organization (WHO) recommends a total of eight ANC visits for pregnant women. However, the ANC coverage rate remains considerably lower among more vulnerable populations, and the quality of care that women receive is inconsistent, often poor, and frequently fails to detect risks in a timely fashion or adequately prepare women for the birth process. While rates of facility-based delivery are on the rise worldwide, disparities persist and the quality of care across facilities remains uneven. Even less information is available on PNC, where services beyond routine immunizations may not be widely available, especially in resource-poor regions. Additionally, limited evidence exists on innovative service delivery approaches and how to effectively scale tested maternal and newborn health (MNH) interventions. This coupled with the fragmented datasets from smaller studies limit our ability to advocate for policy change. The Pregnancy Risk Stratification Innovation and Measurement Alliance (PRiSMA) is implementing a harmonized open cohort study that seeks to evaluate pregnancy risk factors and their associations with adverse pregnancy outcomes, including stillbirth, neonatal mortality and morbidity, and maternal mortality and severe morbidity. The goals are to develop a harmonized data set to improve understanding of pregnancy risk factors, vulnerabilities, and morbidity and mortality and to estimate the burden of these risk factors and outcomes in LMICs. Ultimately, these data will inform development of innovative strategies to optimize pregnancy outcomes for mothers and their newborns.

Patients Pregnant Women With or Without Primary Antiphospholipid Antibody Syndrome

The purpose of the study is to evaluate the ability of placental angiogenesis markers to predict the risk of PE in pregnancy in women with primary APS. To construct reference intervals of placental angiogenesis markers specific to women affected by primary APS in pregnancy by measuring the levels of sFlt-1and PlGF in serum maternal serum and their sFlt-1/PlGF ratio during the trimesters of gestation (I TM, II TM and III TM). For this aim the study will involve recruiting two groups of subjects, one will be cases and one will be controls.

Medically Assisted Fertilization Techniques in Systemic Immunoreumatologic Diseases

Systemic rheumatological diseases often occur in young women of childbearing age and can therefore impact fertility. There are diseases, such as arthritis, which present no contraindication to assisted reproductive techniques (ARTs), because there is no influence on the disease itself if the disease activity at conception is stable. On the other hand, patients suffering from connective tissue diseases, primarily Systemic Lupus Erythematosus (SLE) and patients suffering from primary or SLE-related Anti-Phospholipid Antibody Syndrome (APS), deserve more targeted therapies both in the context of ARTs and in the ensuing pregnancy. To evaluate the response to ARTs in patients with systemic rheumatological diseases, both in terms of reactivation of the underlying pathology and in terms of ARTs outcome.

Successfully Achieving and Maintaining Euglycemia During Pregnancy for Type 2 Diabetes Through Technology and Coaching

The ACHIEVE RCT will measure the effect of the intervention (mHealth app with CGM, provider dashboard, and care team coaching) compared to current standard care (prenatal visits, self-monitored blood glucose, and certified diabetes care and education specialist) on achieving glycemic control (hemoglobin A1c \<6.5% in the third trimester). We hypothesize a 25% absolute increase in the proportion of participants in the intervention group who will meet the target hemoglobin A1c \<6.5% in the third trimester compared to the standard care group

Gestational Diabetes Monitoring and Management

The primary goal is to predict the clinical outcomes of mother and baby using blood glucose and other routinely collected clinical data in pregnancy to predict adverse outcomes at birth in women with GDM. The secondary goal is to develop models to predict optimal blood glucose testing schedules for pregnant women. Exploratory Objectives are (1) to understand patterns of dosage and / or medication choice and (2) to describe different phenotypes of gestational diabetes based on multiple data input.

Commercial or Open Source Closed Loop Impact on Pregnancy Study

The goal of this observational study is to better understand what happens when pregnant people with type 1 diabetes (T1D) use automated insulin delivery (AID) systems. The main questions this study aims to answer are: * What are the maternal and neonatal outcomes with AID system use in pregnancy? * What are the glycemic outcomes with AID system use in pregnancy? * What are the behavioral and emotional outcomes with AID system use in pregnancy? Researchers will compare pregnant people who use commercial AID systems and pregnant people who use open source AID systems to see if outcomes are different with these different types of systems. Participants will be asked to remotely share their AID system data with the research team; complete online surveys regarding behavioral and emotional health; and sign an authorization to release health information to allow the research team to access medical records.

SCRIPT: Sickle Cell Risk in Pregnancy Tool

Sickle Cell Disease (SCD), common in persons of Black ancestry, affects the shape of hemoglobin, the oxygen-carrying part of red blood cells (RBC). It is characterized by many complications, the most dreaded of which are related to pregnancy - affecting both the mother and unborn child. Compared to those without SCD, people with SCD have more adverse pregnancy outcomes (APO): 6x maternal mortality, 2x preeclampsia \& preterm birth, 4x risk of having a baby not growing well in the womb \& stillbirth. There is also greater need for access to care (7x higher hospitalization often multiple times lasting days to months). Yet up to 30% of SCD pregnancies are uncomplicated. Treatments in pregnancy are limited and carry risks. A method to distinguish pregnancies at high-risk of APO that may benefit from these potentially risky treatments, from those likely to be uncomplicated, is urgently needed. To meet this need, the investigators developed a calculator to estimate pregnancy complication risk, using single-centre data. Its accuracy and precision will now be evaluated with international information from several centers by testing the calculator, and adjusting it as needed, using already available pregnancy-data from study centres in several countries. Those age \>16 years, who have a confirmed SCD genotype, pregnancy with one baby, and pregnancy care and birth at a participating study centre will be included. Pregnancy care for the participants will be up to their doctors, with no changes based on the study. SCRIPT - the new tool - will guide future care by predicting who may benefit from specific treatments, reducing harm to low-risk individuals \& will allow selection of high-risk patients for a future trials to determine whether currently available and novel treatments in well-selected patients can improve APO sufficiently to balance treatment-related harms.

Defining, Recognising and Escalating Maternal Early Deterioration (DREaMED)

Every year more than 700,000 women give birth in the United Kingdom. Of these at least 8700 nearly die - called a "near-miss", and 70 die. Many more women suffer harm, often with effects lasting for life. Women from less wealthy areas and particular ethnic groups are more likely to come to harm. "Vital signs" include measurements of blood pressure, heart and breathing rates. Doctors and midwives use tools that score vital signs to spot women becoming unwell. These tools are called "Modified Obstetric Early Warning Scores" (MOEWS). Despite their use, poor outcomes still occur. This may be because MOEWS use only the most recent vital signs. Using extra data like blood tests may help spot unwell people earlier. The study aims to reduce poor outcomes for women giving birth. The study will find better ways of describing, spotting, and treating women becoming unwell. The study have planned four linked projects to develop an electronic advanced maternal obstetric early warning system (eMOEWS). Patient and Public (PPIE) collaborators have developed this work with CI's. The study work closely with them throughout this project. Once the study has completed these four projects, they plan to carry out a trial to assess whether the new eMOEWS leads to better outcomes than the existing tools.