Clinical Research Directory

Study to Assess the Safety, Tolerability, and Preliminary Efficacy of ST266 in Infants With Necrotizing Enterocolitis

The primary objective of this study is to determine the safety and tolerability of two dose levels (0.5 mL/kg and 1.0 mL/kg) of once daily (QD) via IV route of administration of ST266 in treating patients with Bell's stage IIA or higher medical NEC by incidence of treatment emergent adverse events (TEAEs) and SAEs, with a secondary objective to assess preliminary efficacy of the same two dose levels (0.5 mL/kg and 1.0 mL/kg) of QD via IV route of administration of ST266 in treating patients with Bell's stage IIA or higher medical NEC.

A Cohort Study of the Intestinal Microbiota of Premature Infants

Premature infants are at risk for a variety of diseases, the investigators would like to learn more about why some premature babies are at higher risk and some are protected from these diseases. Scientists at UC Davis and other universities have developed new ways to measure the bacteria and a large number of small molecules in specimens of infant blood, urine, stomach fluid and poop and in mother's milk. These discoveries allow us to consider questions that were impossible to answer before these new techniques were developed. One such question is whether the bacteria in the poop of a premature baby can help us predict the baby's risk for developing infection or a common and serious disease of premature infants called necrotizing enterocolitis. A second question is whether the DNA of a premature baby (obtained from saliva with a q-tip) can predict higher risk for diseases of premature babies.

Study of Normal Intestinal Development and Disease in Premature and Term Neonates

Current research on early intestinal development is primarily performed in mouse models. While useful in many other ways, mouse models are not ideal for studying human intestine development as the timing of this process differs between the two species. Further, prior research has demonstrated that some proteins and pathways that are critical in human development have no clear role in mice. This study aims to improve the overall understanding of critical aspects of intestinal development in humans. In addition, this study will investigate the impact of intestinal diseases that are found in the early stages of life such as necrotizing enterocolitis (NEC).

RBC Irradiation, Anemia and Gut Injury

The purpose of this trial is to study the effect that anemia and red blood cell (RBC) transfusions have on oxygen levels in the digestive tracts of extremely low birth weight (ELBW) infants and to look for possible markers in a baby's blood, urine and/or stool that may lead to a better understanding of what makes an ELBW infant at risk for digestive tract problems such as necrotizing enterocolitis.

RIC-NEC Randomized Controlled Trial

Necrotizing enterocolitis (NEC) is a serious intestinal disease of preterm and term neonates which remains a major cause of intestinal failure, and an unsolved clinical challenge in pediatrics. While overall mortality of preterm infants continues to decrease due to improvements in general neonatal care, mortality caused by NEC remains high (up to 30-50%) and survivors suffer from reduced quality of life, and long-term disabilities such as debilitating complications of intestinal failure, poor growth and neurodevelopmental delay. Besides prevention, there have been hardly any innovations in the treatment of NEC which underwent trial evaluation. NEC pathogenesis is multifactorial, but bowel ischemia is known to play an essential role in the development of NEC. Remote ischemic conditioning (RIC) is a therapeutic maneuver that involves brief cycles of non-lethal ischemia and reperfusion applied to a limb, which protects distant organs (such as the intestine) from ischemic damage. The investigators have shown that in preclinical models of NEC, RIC effectively reduces intestinal damage and prolongs survival. The investigators have also demonstrated the safety of RIC in preterm neonates with NEC. Before the investigators can evaluate the effectiveness of RIC in treating neonates with NEC in a Phase III randomized clinical trial (RCT), a Phase II Feasibility RCT must be conducted to evaluate issues related to the enrollment and randomization of neonates, masking of the RIC intervention, and measurement of clinical outcomes. The investigators hypothesize that it is feasible to conduct a multicenter RCT to evaluate RIC during the management of neonates with medical NEC.

WithHolding Enteral Feeds Around Blood Transfusion (International)

The WHEAT International trial is a comparative effectiveness trial exploring whether withholding enteral feeds around the time of blood transfusion in very premature infants (\<30 weeks) will reduce the occurrence of Necrotizing Enterocolitis (NEC). Currently both continued feeding and withholding feeding are approved care practices. The current study will randomize infants from Neonatal Intensive Care Units (NICUs) across Canada and the United Kingdom (UK) into one of the two care approaches (withholding or continued feeds) to determine if any significant outcomes are found.

Early Predictors of Necrotizing Enterocolitis in Neonates

The goal of this project is to identify neonates who are predisposed to Necrotizing Enterocolitis (NEC). the investigators will determine the effectiveness of non-invasive measures as well as biochemical markers to identify neonates early in the disease process. Thus, the investigators aim to identify infants with NEC prior to the onset of symptoms to institute or test treatments in the long term to prevent the progression of the disease in these infants.

A Genome-Wide Association Study for Neonatal Diseases

This is an observational study to identify genetic risks for neonatal diseases, necrotizing enterocolitis (NEC) using genome-wide association study (GWAS) and enterotype investigation. We hypothesize that specific genetic factors and microbiome could predispose preterm neonates for the development of NEC.

Application of Transcriptome Sequencing Combined With Family-Based Whole Genome Sequencing in Improving Precise Diagnosis of Critically Ill Newborns in Northeast China

Background: Birth defects and genetic diseases are major threats to infant health. Many genetic diseases present atypically in newborns, who often have critical conditions, rapid progression, and high mortality. Early diagnosis is crucial but challenging. While next-generation sequencing (NGS) technologies like whole genome sequencing (WGS) and whole exome sequencing (WES) have significantly advanced genetic disease diagnosis, conventional WES/WGS has a long detection cycle. Rapid/ultra-rapid sequencing technologies (rWES/urWES, rWGS/urWGS) offer far-reaching clinical value. Study Objective: This study aims to explore the application of transcriptome sequencing in clinically diagnosing neonatal genetic diseases with negative rWGS results, improve diagnostic rates, assist in early determination of disease causes, provide genetic counseling, and achieve targeted, personalized treatment guidance and prognosis evaluation. Study Design: This is a multi-center cohort study led by the First Hospital of Jilin University, involving at least five clinical medical institutions. The planned sample size is 1,000 cases over three years. The study will include critically ill newborns under three months old, suspected of having genetic diseases based on clinical manifestations or family history, with informed consent from parents or legal guardians. Methods: The study will conduct RNA-seq and joint analysis on 1,000 critically ill newborns with negative family-based rWGS results. The goal is to improve the interpretation of variants of uncertain significance (VUS) and the gene-positive diagnostic rate. It will accumulate disease research big data and conduct integrative genomic analyses based on Pathway and protein-protein interaction (PPI) networks to discover potential new molecular genetic mechanisms and guide new treatment developments. Data Management: Data will be promptly, completely, accurately, and clearly recorded in case report forms and entered into a database system. Data verification, cleaning, and archiving will follow strict procedures to ensure data quality and integrity. Data Analysis: Bioinformatics analysis of sequencing data will include quality control, data filtering, sequence alignment, mutation annotation, variant screening, single-gene mode analysis, and joint transcriptome analysis. Statistical analysis will follow traditional clinical trial methods, with a focus on controlling biases and confounding factors.

Milk Temperature Control and Necrotizing Enterocolitis Risk in Extremely Preterm Infants

Necrotizing enterocolitis (NEC) is one of the most common and severe gastrointestinal emergencies during the neonatal period, especially among preterm infants. In high-income countries such as Finland and the USA, the prevalence of NEC ranges from 2% to 16.58% among very preterm infants (VPIs) and from 6.8% to 10.0% among extremely preterm infants (EPIs). According to the 2022 Annual Report of the China Newborn Collaboration Network (CHNN) from 89 tertiary hospitals, the prevalence of NEC was reported at 14.2% among VPIs and EPIs. Up to half of NEC cases in infants require surgical intervention, with 39.1% of VPIs and 44.5% of EPIs needing surgery. Consequently, NEC-related mortality rates vary significantly, ranging from 21.9% to 42.3% in preterm infants weighing less than 1500 grams (equivalent to VPIs) and from 33.0% to 50.5% in those weighing 500-1000 grams (equivalent to EPIs).

Necrotizing Enterocolitis and Bowel Perforation in Very Preterm Infants - Long-term Follow up

Necrotizing enterocolitis (NEC) is a gastrointestinal syndrome characterized by transmural inflammation and necrosis of the large and/or small bowel and subsequent intramural gas-forming organisms into the intestinal wall. Some preterm infants also develop spontaneous intestinal perforations (SIP) without the classical bowel inflammation/necrosis seen in NEC. NEC and SIP can be challenging to differentiate. Severe cases of both conditions require surgery and often bowel resection, but mortality due to SIP seems lower. Studies looking at "long-term prognosis" of infants with NEC and bowel perforation have mainly assessed outcome until 2-7 years of age. The primary school years is a vulnerable period for ex-preterm children. Disruption in learning and social integration is of great importance for their quality of life (QoL), but little data exist in this age group. Moreover, nutritional deficits (e.g. cobalamin- or iron-deficiency may impact cognitive development, but this has not been investigated in this "high-risk" population in school age. Authors of a recent systematic review on gastrointestinal sequel after NEC-surgery thus called for "more high-quality studies assessing long-term follow-up". In this project we will study the long-term impact of surgery for NEC and bowel perforation in preterm infants, both with a quality of life (QoL) perspective and with a focus on development, growth, nutrition and persistent gastrointestinal problems.

Primary Anastomosis Versus Enterostomy in the Surgical Treatment of Necrotising Enterocolitis

Necrotizing enterocolitis (NEC) is a devastating disease that affects the intestine of premature infants and is the most common surgical emergency in newborns. It is estimated that up to 10% of premature babies can suffer from this condition. Despite aggressive medical treatment, surgical intervention is necessary in up half of the cases for bowel necrosis or perforation and these often represent the more severe form of the disease. The advances in neonatal intensive care and surgical knowledge have resulted in improved survival rate in recent years. For NEC patients with severe disease (i.e.) those with intestinal perforation or gangrenous bowel not responding to medical therapy, surgery with resection of diseased segments is the treatment of choice. Traditional surgical approach would be to resect the diseased bowel segment with formation of enterostomy. However, in a few advanced centres, primary anastomosis after the resection of diseased bowel segment is practised. Retrospective reports of the primary anastomosis approach have shown that this is also a viable option with no increased rate of peri-operative morbidity. It also has the advantage of avoiding a second operation for enterostomy closure. Nonetheless, prospective studies comparing the two approaches are lacking. The proposed study will fill up the following knowledge gap on what the best surgical option for NEC at laparotomy is. The findings will help guide our practice for NEC patients in the future in order to provide them with the best possible and evidence-based care. In this study, the investigators hypothesize that neonates with major NEC undergoing primary anastomosis after surgical resection is not inferior to neonates who have enterostomy, in terms of peri-operative morbidities. Aim of the study is to compare the short term and medium term outcomes of NEC patients requiring surgical intervention who either receive primary anastomosis or enterostomy creation.

PrePhage - Faecal Bacteriophage Transfer for Enhanced Gastrointestinal Tract Maturation in Preterm Infants

PrePhage - Fecal bacteriophage transfer for enhanced gastrointestinal tract maturation in preterm infants This pilot triol has the primary goal of demonstrating the safety of transferring viruses and proteins from healthy term infants to preterm infants born between gestational age (GA) 26 + 0 and 30+6. The long-term goal is to develop a safe and effective treatment to prevent the severe gut disease called necrotizing enterocolitis (NEC). NEC is a common disease in neonatal intensive care units affecting 5-10% of all admitted patients. 15-30% of the affected children die from the disease, and many of the survivors suffer from the effects of extensive gut surgery. While the disease is caused by many different factors, recent research has shown the gut microbiome to be a central factor in the development of NEC. Furthermore, in the recent years special viruses called bacteriophages have shown potential in the treatment of various diseases. By collecting feces from healthy, term infants and filtering it thoroughly, the investigators can provide a treatment that contains practically only viruses, proteins and nutrients. It is our belief that giving the preterm infants a mix of viruses including bacteriophages will prevent NEC. To do this, the investigators will go through 3 stages: 1. Recruiting and following healthy donor infants to study the microbiota and use feces from them to donate in stage 2 and 3 2. Examining the safety of the treatment as well as how it works in preterm piglets 3. Testing the treatment in preterm infants. 10 preterm infants will receive the treatment and 10 preterm infants will receive placebo. The investigators expect to see no serious side effects to the treatment. The investigators hope, but do not expect to be able to see a beneficial effect of the treatment. If this pilot trial shows promising results, it will be followed be a larger clinical trial.

Identification of Clostridium Butyricum and Clostridium Neonatal in the Digestive Microbiota of Premature Infants Before 34 Weeks and Developing or Not Ulcerative Necrotizing Enterocolitis (NEC) During Hospitalization

The study investigators hypothesize that Clostridium butyricum and Clostridium neonatal will be more frequently found in the stool of preterm infants with ulcerative necrotizing enterocolitis compared to healthy matched control infants. Systematic daily samples should show that the kinetics of colonization precedes the onset of the pathology. Finally, the systematic ecological survey at the time of infection could help understand the mode of acquisition and transmission of these bacteria.

Impact of Standardized Skin-to-Skin Care on Clinical Outcomes in Infants Born ≤ 32 Weeks: A Multicenter Study

This study is a multi-center, prospective pre-post clinical study conducted under the leadership of the Turkish Neonatal Society. It aims to investigate the effects of a standardized skin-to-skin care in NICU, initiated early and applied regularly, on recieving exclusive mothers' milk at discharge and clinical outcomes for preterm infants born ≤ 32 weeks of gestation. 1. Primary Objective: To evaluate the rate of receiving exclusive mothers' milk at discharge for infants born ≤ 32 weeks of gestation who have received skin-to-skin care in accordance with the study protocol. 2. Secondary Objective: To evaluate the rates of neonatal sepsis, intraventricular hemorrhage, and necrotizing enterocolitis (stage 2 and above) as well as the length of hospital stay for infants born at or below 32 weeks of gestation who have received skin-to-skin care in accordance with the study protocol.

Human Milk Fortification in Extremely Preterm Infants

This is a randomised controlled multi-centre trial comparing the effect of diet supplementation of a human breast milk-based nutrient fortifier (H2MF®) with standard bovine protein-based nutrient fortifier in 222 extremely preterm infants (born before gestational week 28+0) exclusively fed with human breast milk (own mother´s milk and/or donor milk). The infants will be randomised to receive either the human breast-milk based H2MF® or the standard bovine protein-based nutrient fortifier when oral feeds have reached \<100 ml/kg/day. The randomised intervention, stratified by centre, will continue until the target gestational week 34+0. The infant must not be fed with formula during the intervention period. The allocation will be concealed before inclusion, but after randomisation the study is not blinded. Primary endpoint of the intervention is the composite variable necrotizing enterocolitis (NEC), sepsis and mortality. The enrolled infants are characterised with clinical data including growth, feeding intolerance, use of enteral and parenteral nutrition, treatment, antibiotics and complications collected daily in a study specific case report form from birth until discharge from the hospital (not longer than gestational week 44+0). A follow up focusing on neurological development, growth and feeding problems will be performed at 2 years of age (corrected) and 5.5 years of age.

Spectral Analysis of Bowel Sounds in Preterm Babies of Less Than 32 Weeks of Amenorrhea (WA) as Predictive Factor of Enterocolitis

The recording or bowels is easy and cheap. The investigators wonder if these sounds are modified in babies with high risk of necrotizing enterocolitis. In this study, the investigators suggest to record and do a spectral analysis of 30 seconds of bowel sounds in preterm babies of less than 32WA before and after enteral nutrition, every day until the end of hospitalization. A spectral analysis will be made for each record to determine frequencies of the signal. The investigators will try to determine physiological frequencies and look for modifications in pathological situations.

Qualitative Study of Surgeons With Prospective Patient Follow-up

Necrotising enterocolitis (NEC) is a devastating disease which causes severe bowel inflammation resulting in babies becoming critically unwell. It mainly affects premature babies (who can be born as early as 22 weeks) in the first few weeks of life. A quarter of babies don't respond to intensive care treatment and require surgery to remove bowel which has died to prevent them from getting sicker. Sadly, about a third of the most unwell babies don't survive and those that do have a high incidence of significant long-term health problems. Deciding which babies will benefit from surgery is challenging and there are no objective methods used to do this currently. Surgeons must weigh up the risks and benefits of performing major surgery on a tiny baby in the knowledge that surgery itself may cause harm. This uncertainty causes delays in performing surgery. Those that have a delay are more likely to have a poor outcome. In order to improve these unfavourable outcomes it is essential to understand and define current practice in detail (i.e. indications and timing for surgery) and understand how this may be associated with outcome. These outcomes are both short term, including mortality and ability to tolerate enteral nutrition, and long term which include neurodevelopmental outcomes at 2 years of life. To do this the investigators will undertake a multicentre mixed methods study with qualitative interview of consultant paediatric surgeons shortly after making a decision to operate, or not, on a baby with NEC. The investigators will then take consent from the parents/guardian of the infant to follow-up their clinical outcomes using data linkage to routinely collected data, within the national neonatal research database. Outcomes of interest include survival, feeding outcomes, further surgical procedures and neurodevelopment at 2 years.

IBP-9414 for the Prevention of Necrotizing Enterocolitis - The Connection Study

IBP-9414 will be evaluated in preterm infants with a birth weight of 500-1500g, compared to placebo with regards to efficacy and safety in the prevention of necrotizing enterocolitis.

Probiotic Supplementation in Extremely Preterm Infants in Scandinavia

The primary aim of this research is to determine whether supplementation with probiotics during the first weeks of life reduces the risk of necrotizing enterocolitis (NEC) and neonatal mortality and is safe to use among extremely preterm (EPT) infants born before gestational week 28. P: The study population include EPT infants (n= 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. I: This is a double-blinded multicenter randomized controlled trial where infants in the intervention group will as soon as they tolerate 3 mL breastmilk per feed receive a probiotic combination of Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus diluted in 3 mL breastmilk and given once daily until gestational week 34. C: The control group will receive 3 mL breastmilk without probiotic supplementation (blinded) daily. O: Primary outcome variables is a composite endpoint of incidence of NEC and mortality. Secondary outcomes include incidence of sepsis, duration of hospital stay, use of antibiotics, feeding tolerance, growth, and body composition after hospital discharge. Patient benefit: To provide evidence on the usage of probiotics among EPT infants that are not currently covered by clinical recommendations. As EPT infants have the highest risk for NEC and mortality our results have the potential to change current recommendations and improve patient outcomes, decrease mortality, shorten hospitalization, and decrease overall health-care costs.

PUFAs in Preterm Infants

The research endeavors to examine the critical composition of Polyunsaturated Fatty Acids (PUFAs) in premature infants across different gestational stages and under varying disease conditions, and delineate the metabolic attributes of PUFAs in premature infants and their interplay with the onset of diseases. This study anticipates furnishing a theoretical foundation for the rationalization of PUFAs supplementation in premature infants and for informing strategies related to disease prevention and management.

Early Routine vs. Selective Human Milk Fortification in Extremely Preterm Infants

The aim of the project is to study the effects of fortification (using a Human Milk Donor Fortifier) of an exclusive preterm human milk diet on outcome of extremely preterm neonates, born at less or equal to 27 weeks.

Intestinal Lavage to Promote Enteral Feeding and Prevent Necrotizing Enterocolitis in Extremely Preterm Infants

Optimizing enteral nutrition (EN) is challenging in extremely preterm infants due to feeding intolerance that relates to the functional gastrointestinal immaturity. Early feeding is a safe way to promote postnatal gastrointestinal maturation and, when compared with delayed enteral feeding, provide benefit, such as reduced time to full enteral feedings (TFF) and number of parenteral nutrition (PN) days. Failure to develop oral feeding competence often leads to growth failure, longer hospital stays, dependence on PN and its complications, and influences long-term growth and developmental outcomes. Feeding with human breast milk has a protective effect against necrotizing enterocolitis (NEC) compared with formula, whereas feeding intolerance is one of the early signs of NEC. Delayed passage of meconium is a risk factor for feeding intolerance in preterm very low birth weight neonates and specific meconium microbiota characteristics have been linked to increased risk of NEC. This randomized controlled trial (RCT) aims at evaluating the effect of regular intestinal lavage using normal saline on the TFF and severe complications such as NEC and sepsis, in extremely preterm infants. Investigators aim also to follow children´s neurological development until 5,5 years of age. The study will include one intervention group of 100 subjects that will receive regular rectal washout with normal saline and equal number of control subjects, treated according to current routine. The trial is preliminarily estimated to last between year 2018 and 2022. Investigators will monitor closely for possible adverse events. The results are going to be published in reviewed medical journal.