15 Clinical Trials for Various Conditions
Multiple births in the United States are rapidly increasing in large part due to assisted reproductive technologies. Recent data indicate that multiple births now comprise 3-4.5% of all births in the United States. Pregnant women are at risk for iron (Fe) deficiency anemia yet there are virtually no data on Fe status in women carrying multiples and current recommendations do not necessitate Fe screening among this high risk group. Maternal anemia is known to increase the risk of adverse birth outcomes including preterm birth and low birth weight. Moreover, the developing brain is increasingly recognized to be susceptible to Fe insufficiency in utero and growing data support that suboptimal Fe stores at birth are associated with long-term irreversible cognitive deficits in the offspring. To address these gaps in knowledge the investigators will monitor weight gain, hematological measures, Fe status indicators and serum hepcidin across pregnancy in approximately 120 women carrying twins and triplets. Determinants of maternal anemia will be identified. Neonatal hematological measures will be assessed in cord blood from each neonate at birth for assessment of hematological measures, Fe status and hepcidin. Determinants of neonatal anemia will be identified. Inflammatory markers will be measured in all blood samples and related to outcomes. Stable iron isotopes will be given to a subset of women to assess maternal Fe absorption and fetal Fe uptake.
Neonatal anemia is the most commonly encountered hematologic problem among all neonates cared for in the neonatal intensive care unit (NICU). This project seeks to better understand the pathophysiology and treatment of this challenging and important condition, especially as it affects premature, critically ill very low birth weight (VLBW) infants who require intensive laboratory blood monitoring leading to the need for multiple red blood cell (RBC) transfusions (RBCTX). In the research strategy proposed in Study 1, Aims 1, 2 and 3, recombinant human erythropoietin (Epoetin Alpha, PROCRIT, provided by Janssen Scientific Affairs) will first be administered to 1.0 to 1.5 kg VLBW infants; then comprehensive pharmacokinetics (PK) and pharmacodynamics (PD) data will be systematically gathered and analyzed to identify clinical and laboratory covariate parameters differentiating the infants based on their level of Epoetin Alpha responsiveness. Finally the Epoetin Alpha responsiveness predictors thus determined will be applied prospectively in the Aim 4 Study, a 2 x 2 design in which VLBW infants will be identified as good or poor Epoetin Alpha responders, based on the predictors, and then randomly assigned to receive Epoetin Alpha treatment or no treatment. This will test the central hypothesis: RBCTX can be eliminated in the majority of good Epoetin Alpha responders by optimal administration of Epoetin Alpha, but only marginal reductions in RBCTx will occur in the poor Epoetin Alpha responders. This project challenges the prevailing thinking that the efficacy of Epoetin Alpha dosing in stimulating erythropoiesis is insufficient to eliminate the need for RBC transfusions in VLBW infants. Based on extensive preclinical and clinical PK/PD studies by our PPG team, we contend that previous Erythropoietin treatment studies in VLBW infants were not able to realize the full potential of Erythropoietin to eliminate RBCTX (in contrast to the very successful use of Erythropoietin in adult renal failure patients) because previous VLBW studies were conducted 1) without Epoetin Alpha dosing individualized for the complexities of neonatal erythropoiesis and PK/PD of Epoetin Alpha and 2) without consistent criteria for RBC transfusion, Epoetin Alpha dosing, and patient enrollment. Net Epoetin Alpha responsiveness as reflected in Hb level depends on two components: Epoetin Alpha PD and RBC lifespan (Fig 15). By determining RBC lifespan, we will explain inter-subject variability of Epoetin Alpha responsiveness resulting from one of these components. The fetal lifespan data will be examined for its correlation with gestational age. If the correlation is statistically significant, gestational age will be included in the final selection of covariates for the population PK/PD model to be developed at the end of Infant Study 1. To fully understand the correlation of RBC lifespan with gestational age infants ranging from 22-42 weeks gestational age will be studied. The overall impact of Project 1 will be significant and potentially transformative: the development of a personalized, mechanism-driven approach built on sound principles will improve understanding of neonatal anemia and will be applicable to the care of premature, anemic infants. RELEVANCE Project 1 results confirming our hypothesis that PK/PD optimized Epo treatment is effective in eliminating RBC transfusions administered to a select sub-group of NICU infants will provide fundamental knowledge about neonatal anemia that will reduce the burden of illness and disability caused by this condition. In addition, our results will stimulate researchers to extend our findings to other sub-groups with neonatal anemia, ie, smaller and sicker infants, and will stimulate novel treatments with similar, new biotechnology-produced protein drugs.
OUR OVERALL HYPOTHESIS is that post-transfusion survival of allogeneic and autologous RBCs can be accurately quantified in anemic human infants using biotin-labeled RBCs combined with mathematical modeling that adjusts for confounding factors commonly encountered in neonates. These confounding factors include 1) dilution of labeled RBC as a result of growth stimulated erythropoiesis, anemia stimulated erythropoiesis, and blood transfusion; 2) loss of labeled RBC due to laboratory phlebotomy; and 3) variable RBC life spans resulting from RBCs having been produced at different developmental periods and under varying rates of erythropoiesis. In contrast to infants, adjustment for these factors is not necessary in healthy adults under conditions of steady state erythropoiesis. Instead in adults, RBC survival is typified by a linear decline in concentration of labeled RBCs over time. When this line is extrapolated to zero concentration, the intercept with the time axis represents the mean potential lifespan (MPL) of RBCs. (\<7 d) and stored (\>21 d) allogeneic adult RBCs transfused in the same infant.
Objectives: 1) To determine risk factors for fetomaternal hemorrhage. 2) To identify a cost-effective method to detect fetomaternal hemorrhage prior to significant fetal anemia. Significance/Background: Fetomaternal hemorrhage (FMH) is a condition in which occurs when the placenta transfers blood from the fetus to the mother. Normally, nutrition and gasses pass from mother to baby through the placenta and only waste products pass from baby to mother through the placenta. Whole blood cells do not normally cross the placenta in significant amounts. Mild FMH, where a small amount of whole blood passes from fetus to mother but does not hurt the mother or baby, occurs in about 75% of pregnancies. A pregnant woman does not know this occurs. It is only discovered if a special blood test that is labor-intensive to perform and difficult to interpret called the Kleihauer-Betke acid elution test is done. As mild FMH hurts no one, this test is not part of routine care. In most cases, testing is done only if a baby is born sick with unexplained anemia. Severe FMH, which can cause the baby to become sick from anemia (low red blood cell count) is caused by large blood loss into the mother, occurs in only 1-3 per 1000 births. Severe anemia caused by FMH can result in death of the baby before or after birth, or significant illness in the newborn period. Short term problems for the baby include difficulty breathing, difficulty maintaining blood pressure, and difficulty providing oxygen to all parts of the body. This can cause multiple problems with the function of internal organs including the liver, kidneys, intestines, and brain. Babies who become sick from severe FMH can develop long-term problems including cerebral palsy (a lifelong problem with body movements) and/or mental retardation. It is not known why some pregnancies are affected by FMH and others are not. It is thought that FMH may occur more frequently now than in the past, but no one knows why. If identified early, FMH is readily treatable by blood transfusion of the baby before or after birth and/or early delivery. Current laboratory testing for FMH is difficult and expensive. There is great need identify high risk patients early in pregnancy in order to treat the condition before the baby gets sick. Approach: Five hundred women will be asked to participate in the study at the time they are admitted to the Mount Sinai labor floor for delivery at term. After birth, newborns of study mothers will be tested for anemia. Mothers of anemic babies will donate blood for confirmation of FMH by established laboratory methods as well as for development of a new laboratory screening protocol. All mothers will provide medical, social, environmental, and full pregnancy history. Risk factors for FMH will be identified by statistical analysis of this information.
This study evaluates the relationship between anemia and stool microbiota in premature infants. It also evaluates the relationship between blood transfusion and stool microbiota.
The objective of this trial is to compare both strategies (Expectative Vs Fetoscopic laser surgery) for patients with stage 1 TTTS and favorable obstetrical parameters in an international randomized controlled trial. This trial will answer an important question and will help in the management and tailoring of surgical indications in stage 1 TTTS.
This study tested the safety and efficacy of transfusing erythropoietin (Epo) and iron in infants of \<1,250g birth weight. For infants 401-1,000g birth weight, we tested whether early erythropoietin (Epo) and iron therapy would decrease the number of transfusions received. For infants 1,001-1,250g birth weight, we tested whether early erythropoietin (Epo) and iron therapy would decrease the percentage of infants who received any transfusions.
This is a Phase 2, multiple ascending, dose-finding, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, health-related quality of life, tolerability, pharmacokinetic, pharmacodynamic, and immunogenicity, of up to 3 dose regimens of ALXN1830 administered subcutaneous(ly) (SC) in the treatment of WAIHA. This study will include 2 randomized, double-blind, placebo-controlled cohorts (Cohorts 1 and 2) to evaluate an 8-week treatment regimen, and an optional third open-label cohort (Cohort 3) to evaluate an alternative 12-week dosing regimen. Participants may continue participation in this study at the participant's and investigator's discretion in an open-label extension (OLE) period, consisting of monthly visits to observe participants for relapse, which will require going back on active treatment.
Erythroferrone (ERFE) is a recently identified iron-regulatory hormone that couples iron homeostasis to erythropoiesis but at this time there are no human data on this hormone in pregnant women and their neonates. The investigators hypothesize that ERFE is a sensitive biomarker of iron deficiency and anemia in pregnancy and neonates, and that it mediates the feedback mechanism to correct iron deficiency and anemia. To address this research gap, the investigators will measure ERFE in maternal serum, umbilical cord serum and placental tissue using an existing biospecimen archive.
Assess ability of Masimo SpHb sensor to demonstrate robust performance on various sensor application sites on neonates/infants
This study aims to determine how maternal Fe status influences placental and neonatal Fe status in pregnant adolescents and to assess the impact of the Fe endowment of birth on functional outcomes as assessed by auditory brainstem responses within 48 h of delivery in neonates born to these adolescents.
The purpose of this research study is to evaluate the safety of the drug Etanercept (Enbrel) and to determine if this drug can help in the treatment of early bone marrow failure in patients with Fanconi anemia.
The purpose of this study is to determine whether the timing of the clamping of the umbilical cord after delivery has an impact on neonatal hemoglobin and hematocrit, tests that determine the number of red cells in the blood and their ability to carry oxygen. The study hypothesis is that delaying cord clamping until cord pulsation has ceased will increase the neonatal blood volume and thereby increase the hemoglobin and hematocrit. We propose to recruit 150 women who present for vaginal delivery at Tulsa Regional Medical Center. Half of the women will be randomly assigned to the immediate clamping group, which will entail clamping of the umbilical cord within six seconds of delivery of the fetal shoulders. The other half of the volunteers will be assigned to the delayed clamping group, which will entail clamping the cord after a palpable pulse has ceased, or after 10 minutes. The infants of mothers in both groups will have blood drawn for a hemoglobin and hematocrit at the time of the routine PKU heel stick, usually is performed within 18-24 hours of delivery. Statistical differences between the blood counts of infants in the control and study groups will be compared using independent samples t tests.
Hypothesis: That a high hemoglobin threshold for transfusion in extremely low birth weight (ELBW) infants is associated with a lower rate of survival without severe morbidity (defined as one or more of retinopathy of prematurity, bronchopulmonary dysplasia, or periventricular leukomalacia/ventriculomegaly). Primary Objective: To determine whether either a liberal or more restrictive threshold of hemoglobin level for red cell transfusion in ELBW infants is safer, by randomizing to either a high transfusion hemoglobin threshold or a low transfusion hemoglobin threshold. Follow-up at a corrected age of 18 months represents a conventional age at which to first assess neurodevelopmental outcomes, and to predict long-term outcomes.
The objective of the TOP trial is to determine whether higher hemoglobin thresholds for transfusing ELBW infants resulting in higher hemoglobin levels lead to improvement in the primary outcome of survival and rates of neurodevelopmental impairment (NDI) at 22-26 months of age, using standardized assessments by Bayley.