Clinical Research Directory

Vagal Stimulation Therapy and Preeclampsia

Preeclampsia is one of the most common and serious complications of pregnancy, affecting both the mother and baby. It is a condition characterized by high blood pressure and can lead to severe complications, including neurological issues and reduced blood flow to the placenta. Preeclampsia is responsible for a significant number of maternal and perinatal deaths worldwide, with an estimated 14% of maternal mortality in Mexico linked to this condition. Recent research suggests that disruptions in the body's autonomic nervous system, specifically the balance between the sympathetic and parasympathetic systems, play a role in the development of preeclampsia. The vagus nerve, which is part of the parasympathetic system, has been shown to regulate inflammation and blood pressure. Stimulating this nerve through pharmacological, magnetic, electrical, or physical therapy techniques has shown promise in preclinical models for improving blood pressure control and reducing complications associated with preeclampsia. Trigger point release therapy modulates the nervous system by reducing sympathetic activity, promoting blood vessel relaxation, lowering heart rate, and enhancing circulation. When combined with standard antihypertensive treatment, this approach may offer additional benefits for blood pressure regulation. This study aims to evaluate the effects of vagal autonomic stimulation physiotherapy using trigger point release therapy as a complementary treatment for pregnant women with preeclampsia. Participants will be randomly assigned to receive either standard antihypertensive treatment with positional release therapy (control group) or the same treatment combined with vagal stimulation physiotherapy (intervention group). Researchers will assess the intervention's effectiveness in controlling blood pressure and improving overall maternal and fetal health outcomes. By investigating this non-invasive, drug-free approach, this study aims to offer new strategies for managing preeclampsia, potentially improving maternal and fetal health while reducing reliance on medication.

PI4 - A Trial Assessing Metformin to Prolong Gestation in Preterm Preeclampsia

Preterm preeclampsia is a severe condition for both the mother and the fetus. Currently, the only treatment available to stop disease progression is termination/delivery of the fetus and placenta. Therefore, preterm preeclampsia carries the highest rates of neonatal morbidity and mortality due to iatrogenic preterm birth. There is evidence suggesting metformin, a drug commonly used to treat diabetes in and outside pregnancy, may be able to counter the pathophysiology of preeclampsia, raising the possibility that it could be used to treat the condition. This multi centre double blind randomised controlled trial aims to investigate if metformin can prolong gestation, lower neonatal length of stay and increase birthweight in a Nordic setting.

Assessment of Volume Status in Preeclampsia Post- SpinalAnasthesia:Utilizing Ultrasound " Evaluation of Lung and Inferior Vena Cava"

Primary aim Assess the accuracy and reliability of ultrasound evaluation of lung and inferior vena cava in determining volume status post-spinal anesthesia in pre-eclampsia patients. Measure the correlation between ultrasound findings and the traditional methods. Determine if ultrasound evaluation can predict fluid responsiveness and guide fluid management in this population. Secondary aim The secondary outcomes are: Investigate the association between volume status as determined by ultrasound and clinical outcomes such as maternal morbidity, neonatal outcomes, and length of hospital stay. Explore the feasibility and practicality of incorporating ultrasound evaluation into routine clinical practice for volume assessment in pre-eclampsiapatients post-spinal anesthesia. Consider patient satisfaction and acceptance of ultrasound evaluation compared to traditional methods.

Continuous Positive Airway Pressure (CPAP) for Sleep Apnea in Pregnancy

A randomized controlled trial of 1,500 women to assess whether treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) in pregnancy will result in a reduction in the rate of hypertensive disorders of pregnancy.

Vitamin D Supplementation Among Pregnant Women in Uganda for the Prevention of Hypertensive Disorders in Pregnancy, and Other Adverse Maternal and Foetal Outcomes

The goal of this randomised controlled trial is to investigate if vitamin D supplementation among pregnant women in Uganda prevents adverse maternal and foetal outcomes, with special emphasis on preeclampsia. The main question it aims to answer is if Vitamin D supplementation, administered as oral vitamin D₃ at a dose of 2,000 IU once daily, from the time of recruitment to the time of delivery, reduces the incidence of preeclampsia, eclampsia and HELLP syndrome in pregnant women attending ANC at St. Mary's Hospital, Lacor, such incidence being monitored up to six (6) weeks after delivery. Researchers will compare the effect of oral 2.000 IU vitamin D daily (intervention group) vs. oral placebo daily (control group) on the prevalence of adverse maternal and foetal outcomes.

Spironolactone to Improve Pregnancy-Associated Hypertension Trajectories

The hypertensive disorders of pregnancy (preeclampsia and gestational hypertension) are associated with increased long-term maternal risk of developing cardiovascular disease. Recent evidence suggests that activation of the mineralocorticoid receptor promotes ongoing susceptibility to hypertension in women following hypertensive disorders of pregnancy. In addition, women with overweight/obesity are at increased risk for progression to chronic hypertension after experiencing hypertensive disorders of pregnancy. Among women with hypertensive disorders of pregnancy and pre-pregnancy overweight/obesity, the investigators will conduct a randomized trial to test the effect of pharmacologically blocking the mineralocorticoid receptor for three months after delivery on blood pressure and cardiac remodeling at nine months postpartum.

Dietary Salicylates and Preeclampsia

Preeclampsia (PE) is an important pregnancy complication and cause of maternal and perinatal mortality and morbidity. The underlying etiology and pathophysiology of preeclampsia is incompletely understood but it involves dysfunctional cytotrophoblastic invasion, placental ischemia, and release of inflammatory and endothelial mediators. Placenta dysfunction in PE is related to angiogenic balance. Currently, therapeutic options for the prevention and treatment of PE are limited. It is known that the risk of PE is reduced by low-dose aspirin. Therefore, the influence of salicylates on the development of PE seems to need to be investigated. This project plans to examine the preventive effects of food sources of salicylic acid and compare their effects with aspirin. Therefore, the aim of the present study is thus answer the following questions. whether the maternal dietary intake of salicylates is related to placental angiogenesis; 2. whether naturally occurring salicylates have the same effects on preeclampsia development and placental angiogenesis as aspirin. To answer these questions we plan to carry out a human study with pregnant women. Due to the above the planned research aims to determine the association between maternal dietary intake of salicylates and placental angiogenesis and the risk of preeclampsia development. Although PE remains an incurable disease, the results of this project will enable the development of dietary recommendations for the prevention and treatment of preeclampsia. Moreover, the results of this study may be useful in lowering the cost of maternal and fetal complications from preeclampsia and the cost of their hospitalization.

Investigation of the Role of Internal Jugular Vein Collapsibility Index in Predicting Spinal Anesthesia-Induced Hypotension in Preeclamptic Parturients

This prospective, single-center observational study aims to evaluate the predictive value of the internal jugular vein collapsibility index (IJVCI) for spinal anesthesia-associated hypotension in preeclamptic parturients (gestational age ≥28 weeks) undergoing cesarean delivery classified as Lucas category 3-4. Preoperative IJVCI will be measured using ultrasonography before spinal anesthesia during spontaneous and deep respiration. The incidence of hypotension within the first 20 minutes after spinal anesthesia will be recorded. The diagnostic performance of IJVCI in predicting hypotension will be analyzed.

Placental Imaging Techniques

The goal of this proof-of-concept, case-control, clinical trial is to evaluate the efficacy of using two newer ultrasound technologies, quantitative ultrasound (QUS) and ultrafast power Doppler imaging (uPDI), to evaluate the health of the placenta, visualize blood flow through the placental vasculature by color Doppler imaging in singleton pregnancies with and without fetal growth restriction (FGR). * Our primary objective is to investigate the ability of using these ultrasound technologies to distinguish healthy pregnancies from those affected by FGR, a condition characterized by a fetal weight below the 10th percentile for the gestational age or abdominal circumference of the pregnancy. * Secondary aims include longitudinal evaluation of differences in QUS and uPDI imaging over gestation and changes in these measures with evolution of utero-placental insufficiency including with the development of abnormal umbilical-artery Doppler testing, diagnosis of severe FGR, identification of stillbirth, and detection of preeclampsia or preterm birth. Investigators will compare QUS/uPDI imaging and values in pregnancies determined to be healthy by approved, standard-of-care growth ultrasounds to those diagnosed with FGR. Participants will receive research ultrasounds with the experimental Verasonics Vantage 256 system (Verasonics, Inc, Kirkland, WA) utilizing uPDI/QUS every three weeks following their routine growth ultrasound evaluation until delivery. Demographic, obstetric, and delivery-related information, as well as portions of subjects' past medical history will be utilized by researchers to further contextualize imaging and variables gathered during the research ultrasounds.

Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes

This multicenter observational cohort study aims to evaluate whether estimated first-trimester risk of preeclampsia (PE) is associated with subclinical atherosclerosis, cardiovascular risk profile, and cardiovascular events in women with type 1 diabetes (T1D) at least 3 years after pregnancy. Women with T1D and at least one prior pregnancy with documented first-trimester PE screening will be classified as high or low PE risk according to validated multivariable algorithms. The presence of carotid plaques, cardiometabolic risk factors, and incident cardiovascular events will be assessed during a study visit.

Progesterone Preeclampsia

This randomized controlled trial evaluates whether nightly vaginal micronized progesterone (400 mg) initiated before 12 weeks' gestation reduces the incidence of preeclampsia in low-risk pregnant individuals. Participants will be randomly assigned (1:1) to receive either vaginal progesterone through 16 weeks' gestation or routine prenatal care without progesterone. Maternal and neonatal outcomes-including development of preeclampsia, obstetric complications, gestational diabetes, preterm birth, and neonatal morbidity-will be collected via chart review. The study aims to determine whether early progesterone supplementation decreases the risk of preeclampsia.

MumCare: Mum's Cardiovascular Health for Life

The goal of this randomized clinical trial study is to test the potential benefits of eHealth-assisted follow-up after pregnancy complications that confer and increased risk for premature cardiovascular (CV) disease. The overarching aim is to improve short- and long-term CV health in women following pregnancy complications associated with increased risk of CV disease (hypertensive disorders of pregnancy and gestational diabetes). The investigators will develop and test a novel, personalized and user co-designed digital eHealth companion ("app") and test the app in a clinical randomized control trial. The group randomized to app use will get access to the app prior to delivery or within the first weeks postpartum, whereas the control group will not get access to the app, but receive ordinary follow-up. Both groups are invited to a comprehensive cardiovascular follow-up 14-18 months post delivery. The primary objective is to assess whether the rate of 1-year postpartum follow-up at the general practitioner's is increased with MumCare app access. Secondary objectives are to assess: 1. expectations of (and satisfaction with) postpartum eHealth-assisted technologies, 2. if health perception, sense of empowerment (self-management evaluation and general self-efficacy), modifiable risk factors for CV disease (including hypertension, dyslipidemia, blood sugar control, smoking, weight, physical activity), CV findings (including non-invasive hemodynamics) and biomarkers are affected by MumCare app use.

HOME: Home Monitoring of High-risk Pregnancies

High-risk pregnancies often require long-term hospitalization or outpatient maternal and/or fetal monitoring, placing a burden on patients, hospital resources and society. The demand for intensified pregnancy surveillance and interventions is increasing, due to the increased prevalence of risk factors like obesity and advanced maternal age, as well as altered guidelines resulting in increasing labor induction rates.The main aims of the HOME study (Home monitoring of pregnancies at risk) are to assess if home monitoring of selected high-risk pregnancies for maternal and fetal wellbeing is feasible, safe (in a clinical trial), cost-efficient, and simultaneously empowers the users.

Kynurenine Concentrations During Pregnancy in Women With or Without Chronic Kidney Disease - A Prospective Multicenter Study

Chronic kidney disease (CKD) affects more than 10% of the population worldwide and represents the second most important risk factor for preeclampsia, a life-threatening complication of pregnancy responsible for approximately 80,000 maternal and 500,000 perinatal deaths each year. Experimental studies have suggested a causal link between CKD, relative kynurenine deficiency during pregnancy, and preeclampsia development. Kynurenine, a tryptophan metabolite, plays a central role at the materno-fetal interface, supporting placental energy production, maternal-fetal immune tolerance, and placental perfusion. This study will prospectively assess and compare longitudinal kynurenine concentrations in pregnant women with and without CKD, and evaluate their associations with maternal and fetal outcomes.

Vascular Effects of High-Salt After Preeclampsia

Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy. Importantly, women who had preeclampsia have an exaggerated vascular responsiveness to hypertensive stimuli, such as high-salt intake, compared to women who had a healthy pregnancy. The reason why this occurs is unclear but may be related to impaired endothelial function and dysregulation of the angiotensin system that occurs during the preeclamptic pregnancy and persists postpartum, despite the remission of clinical symptoms. While the association between a history of preeclampsia and vascular dysfunction leading to elevated CVD risk is well known, the mechanisms underlying this dysfunction remains unclear. The purpose of this study is to examine the role of vascular mineralocorticoid receptor, the terminal receptor in the angiotensin system that contributes to blood pressure regulation, in mediating exaggerated microvascular endothelial dysfunction before and after a high-salt stimulus. This will help us better understand the mechanisms of microvascular dysfunction these women, and how inhibition of these receptors may improve microvascular function. In this study, we use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) we examine the blood vessels in a nickel-sized area of the skin.

Effects of High Altitude on AMPK Activation

Pregnancy elicits adaptive changes in uteroplacental blood flow, which are altered at high altitude and may contribute to the observed 3-fold increase in intrauterine growth restriction (IUGR) and preeclampsia (PreE). The investigators propose to collect myometrial, cord blood, and placental tissue samples from women at high altitude (Summit County) and low altitude (Denver) in Colorado in order to determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries (MA). If altered MA vasoreactivity is found, further studies may be able to link these changes to the increased rates of PreE and IUGR at altitude and contribute to the understanding of these two disorders.

Topefilgrastim Injection in the Treatment of High-Risk Pregnant Patients With Preeclampsia

This study is an open-label, prospective investigation designed to enroll 100 high-risk pregnant subjects with preeclampsia (PE). Participants will be allocated in a 2:2:1 ratio to one of three groups: the Topefilgrastim 0.5mg/biweekly group, the Topefilgrastim 1mg/biweekly group, or the control group, based on investigator judgment and patient preference. The overall study consists of three parts: a screening period, a treatment period, and a follow-up period.

LDA and LMWH vs LDA Alone in High-risk Patients for Preeclampsia Prevention

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. Low-dose aspirin started in the first trimester reduces the risk of preeclampsia in high-risk women. Low molecular weight heparin (LMWH) has shown potential benefits in addition to aspirin for preventing preeclampsia through its anticoagulant, anti-inflammatory, and endothelial protective effects. However, current evidence is limited and conflicting regarding the added value of LMWH to aspirin. This randomized controlled trial aims to evaluate the efficacy of combined aspirin and LMWH, compared to aspirin alone, for reducing the incidence of preeclampsia in high-risk gravidas.

Optimizing Preeclampsia Postpartum With Point-of-care Ultrasound

This study explores a novel approach to improving care for postpartum patients with preeclampsia, a pregnancy-related condition characterized by high blood pressure, protein in the urine, and organ dysfunction. Preeclampsia affects up to 9% of pregnancies and can progress to include complications of seizures, stroke, and even death. Over 60% of patients with preeclampsia continue to experience high blood pressure at the time of discharge from their delivery hospitalization, and many of these patients require blood pressure medications for up to 6 months postpartum. Even with blood pressure medications, many of these patients are readmitted to the hospital within six weeks of delivery. In this study, the investigators will utilize point-of-care ultrasound (POCUS), a quick and non-invasive, bedside imaging strategy, to look for signs of excess fluid accumulating in the lungs and venous system of postpartum patients with preeclampsia. Because excess fluid has the potential to worsen blood pressure, subjects with evidence of this on POCUS would be treated with a diuretic medication called furosemide (either orally or intravenously) within 24 hours of delivery. The investigators' main goal is to determine whether using POCUS can help physicians make better treatment decisions and improve short-term outcomes for postpartum patients with preeclampsia. The investigators' aim to achieve faster recovery of blood pressure, reduce the need for blood pressure medication at hospital discharge, and lower the rates of hospital readmission for those with preeclampsia. This study could significantly enhance the overall care and health of postpartum patients.

Multiparametric Assessment of Maternal Vascular Function in the Prediction of Hypertensive Disorders of Pregnancy

The present study is a single-centre prospective study that will enrol pregnant women during their first trimester of pregnancy (11+0 - 13+6 weeks of gestation). During pregnancy, women will undergo standard clinical evaluation and management. During the two study visits (enrollment and 24+0 - 27+6 weeks of gestation) the investigators will perform arterial tonometry (Pulsepen) and in vivo darkfield microscopy (Glycocheck) to evaluate endothelial and vascular function. A urine sample and a blood sample for specific study analyses on metabolic profile, endothelial and angiogenic markers will be collected. Pregnancy outcomes will be collected at delivery and five years after delivery all the participants will be interview to collect long-term cardiovascular outcomes. Serum endothelial and angiogenic markers will be evaluated only in participants who will develop hypertensive disorders of pregnancy and in an equal number of controls matched for age and body mass index at the time of conception.

Personalized Care for Prenatal Stress Reduction & Prevention of Preterm Birth (PTB) Disparities

The goal of this clinical trial is to learn if a personalized prenatal support program \[(Personalized Toolkit Building a Comprehensive Approach to Resource optimization and Empowerment in Pregnancy \& Beyond, (PTBCARE+)\] works to lower stress and lower the risk of early delivery in pregnant individuals at high-risk for delivering preterm. The main question\[s\] it aims to answer are: * Does the PTBCARE+ patient support program lower patient-reported stress levels during pregnancy? * Does the PTBCARE+ patient support program improve biologic measures of stress during pregnancy? * Does the PTBCARE+ patient support program result in a higher chance of delivering a healthy baby at or close to full term? Researchers will compare people who participate in the PTBCARE+ patient support program to those receive usual care to see if the PTBCARE+ patient support program lowers patient-reported stress, improves biologic measures of stress, and increases the chance of delivering a healthy baby at or close to full term. Participants will be randomly assigned to receive the PTBCARE+ patient support program or usual prenatal care. All participants will be asked to: * complete 2 study visits during pregnancy - including completing electronic surveys, providing a blood and urine sample, measuring the heart rate variability by a clip or the ear or finger, and body composition evaluation using a simple scale-like device. * complete one study visit postpartum that includes completing electronic surveys, and measuring heart rate variability. Blood and urine sample collection and body composition evaluation via InBody scale are optional at the postpartum visit. People who are randomly assigned to receive the PTBCARE+ support program will receive several resources to help them during pregnancy. These things include items such as: * a stress reduction toolkit; * access to an online website that can also be downloaded as a smart phone app; * the option to receive an electronic massage while in clinic, and more. * additional support gifts provided at routine clinical appointments People who are randomly assigned to receive usual prenatal care will not receive any additional support resources from the study during pregnancy.

Evaluation of sFlt-1/PlGF Ratio ,OPG and sEng as Predictive Biomarkers in the Diagnosis and Treatment Evaluation of Preeclampsia

his study investigates the effectiveness of three specific biological markers (biomarkers) in the blood-the sFlt-1/PlGF ratio, soluble endoglin (sEng), and osteoprotegerin (OPG)-to better diagnose and monitor preeclampsia. Preeclampsia is a serious pregnancy complication characterized by high blood pressure and potential organ damage that affects 2-8% of pregnancies worldwide

MR and Inflammation After Preeclampsia

The purpose of this investigation is to examine the role of inappropriate mineralocorticoid receptor activation in endothelial dysfunction and vascular inflammation in otherwise healthy women with a history of preeclampsia. The main questions it aims to answer are: 1. Does overactivation of the mineralocorticoid receptor contribute to reduced endothelial function in women who had preeclampsia? 2. To what extent does the mineralocorticoid receptor mediated exaggerated production of inflammatory cytokines in immune cells from women who had preeclampsia? Participants will visit the research laboratory for 2 experimental visits: * Visit 1: Skin blood flow will be measured using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) to examine blood vessels in a nickel-sized area of the skin. * Visit 2: Endothelial cells will be collected from an antecubital vein.

Exosome Cargo From Preeclampsia Patients

Although extensively studied, the cause of preeclampsia remains uncertain other than it is thought that the placenta plays a critical role in the development of preeclampsia. Recent data revealed that exosomes released from the placenta could cause preeclampsia by transporting specific cargo responsible for the pathophysiological changes associated with the systemic disease. By isolating these exosomes from maternal blood and placental tissue in patients diagnosed with preeclampsia and studying their biochemical, cellular and molecular mechanism in an animal model, the investigators hope to elucidate the critical role that exosomal cargo plays in the development of preeclampsia and cardiovascular remodeling. This will be accomplished by obtaining patient samples from volunteers delivering at the Women and Infants Center and taking the samples to the lab for quantification, characterization, and identification of key functional roles through in/ex vivo, in vitro, and profiling studies. The investigators believe this work will be valuable as hope exists to define the functional role exosomes play in the development of preeclampsia that leads to cardiovascular remodeling. Data from this study will shed more light on the functional role of exosomal cargo in normal and pathological pregnancies and point towards novel therapeutic intervention strategies for preeclampsia associated with cardiovascular disease.