Role of Urinary Claudin-2, Caveolin-1, and EGF as Diagnostic Biomarkers of Necrotizing Enterocolitis in Preterm Neonates
Concentrations of Urinary Claudin-2, Caveolin-1, and Epidermal Growth Factor (EGF) as the Prototypes of Non-Invasive Biomarkers in the Diagnosis of Necrotizing Enterocolitis in Preterm Neonates
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observational
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Brief Summary
Our study aims to determine the differences in the concentration of urinary claudin-2, caveolin-1, and epidermal growth factor (EGF) as non-invasive biomarkers in the diagnosis of Necrotizing Enterocolitis (NEC). We compare the concentration of urinary claudin-2, caveolin-1, and EGF between preterm neonates at risk of NEC and healthy term infants as the basis for determining NEC biomarkers with the most optimum sensitivity and specificity. This analytical observational study is based on biomolecular profiling with a prospective cohort design approach. The research subjects are a group of preterm neonates (gestational age of 28-34 weeks) who were admitted in Perinatology Unit, Department of Pediatrics, Saiful Anwar General Hospital, Malang and whom diagnosed with NEC using Bell's criteria and serum TGF-β levels. Subjects are selected by consecutive sampling and single-blind analysis was performed in the Laboratory of Bioscience and Biomedicine, Faculty of Medicine, University of Brawijaya. During the research process, groups of preterm and term neonates would be observed and their clinical development followed. The collection of biologic samples would be taking 10 cc of urine and 40 mg of feces on day-5 (D5) and 7 (D7). The consecutive manner of urinary sampling was regarded to assess whether there was a time-related protein expression in the course of the NEC process. Faecal samples would be assessed for microbiota profile analysis described by the ratio of Proteobacteria: Firmicutes and Bacteroidetes to represent dysbiosis process in NEC. After 7 days, the subjects would be grouped into a group of preterm neonates with NEC, a group of healthy term neonates as a control, while a group of preterm infants at whom during the course of the study did not develop NEC, would be assigned to group of premature neonates without NEC. Urinary protein concentrations from the three groups would then be analyzed and adjusted with normalized creatinine, so that the levels of these three proteins could be assessed quantitatively using the ELISA (Enzyme-Linked Immunosorbent Assay) method. The results would be compared with the microbiota profile as the golden standard for NEC cases. Through statistical tests, sensitivity, specificity and cut-off of selected protein levels would be assessed as diagnostic biomarkers of NEC.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for all trials
Started Mar 2022
Shorter than P25 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 17, 2022
CompletedFirst Submitted
Initial submission to the registry
April 12, 2022
CompletedFirst Posted
Study publicly available on registry
April 19, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2022
CompletedApril 19, 2022
April 1, 2022
2 months
April 12, 2022
April 12, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Change of Urinary Claudin-2 Concentration
Concentrations of claudin-2 protein on Day-5 and Day-7 identified in the urine of neonates with necrotizing enterocolitis (NEC), stated numerically in ng/ml.
Day-5 and Day-7 of age
Change of Urinary Caveolin-1 Concentration
Concentrations of caveolin-1 protein on Day-5 and Day-7 identified in the urine of neonates with necrotizing enterocolitis (NEC), stated numerically in pg/ml.
Day-5 and Day-7 of age
Change of Urinary EGF Concentration
Concentrations of EGF protein on Day-5 and Day-7 identified in the urine of neonates with necrotizing enterocolitis (NEC), stated numerically in pg/ml.
Day-5 and Day-7 of age
Bell's stage of NEC
Bell's stage of NEC are categorized into stage IIa, IIb, IIIa, and IIIb.
Day-1 (Baseline)
Secondary Outcomes (3)
Change of fecal microbiota profile
Day-5 and Day-7 of age
Change of Urinary Normalized Creatinine Level
Day-5 and Day-7 of age
Serum TGF-β Concentration
Day-1 (Baseline)
Study Arms (3)
Preterm neonates with NEC
Preterm neonates with gestational age of 28-32 weeks and diagnosed with Necrotizing Enterocolitis based on Bell's modification criteria.
Preterm neonates without NEC
Preterm neonates with gestational age of 28-32 weeks and without Necrotizing Enterocolitis based on Bell's modification criteria.
Healthy term neonates
Term neonates with gestational age of 37-42 weeks without any comorbidities.
Interventions
A sequential non-invasive urinary molecular profiling for protein, i.e. Claudin-2 as potential marker for enterocyte tight junction disruption, would be analyzed quantitatively with ELISA and then compared between groups to assess the optimum sensitivity and specificity.
A sequential non-invasive urinary molecular profiling for protein, i.e. Caveolin-1 as potential marker for enterocyte tight junction disruption, would be analyzed quantitatively with ELISA and then compared between groups to assess the optimum sensitivity and specificity.
A sequential non-invasive urinary molecular profiling for protein, i.e. epidermal growth factor (EGF) as potential marker for tight junction protective regulator, would be analyzed quantitatively with ELISA and then compared between groups to assess the optimum sensitivity.
Eligibility Criteria
The target population of this study are neonates that would be categorized into three groups, i.e. preterm neonates with NEC, without NEC, and healthy term infants. The subjects are recruited from Perinatology Unit, Saiful Anwar General Hospital from March-May 2022.
You may qualify if:
- Premature neonates with 28-34 weeks' gestational age
- Admitted in Perinatology Unit, Saiful Anwar General Hospital, Malang
- Parents/guardians have agreed and signed the informed consent of the study
- Neonates receive nutrition from breast milk or breast milk predominance
- NEC was diagnosed using Bell's modification criteria.
- Premature neonates with 28-34 weeks' gestational age, admitted in Perinatology Unit, Saiful Anwar General Hospital, Malang. Parents/guardians have agreed and signed the informed consent of the study. Neonates receive nutrition from breast milk or breast milk predominance.
- Term neonates with 37-42 weeks' gestational age, admitted in Perinatology Unit, Saiful Anwar General Hospital, Malang. Parents/guardians have agreed and signed the informed consent of the study. Neonates receive nutrition from breast milk or breast milk predominance.
You may not qualify if:
- Treated neonates who died during the study before the diagnosis of NEC was established
- Neonates whom require surgery during the study
- Parents/guardians stated that they were not willing to participate in the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Saiful Anwar General Hospital
Malang, East Java, 65111, Indonesia
Biospecimen
Biospecimen to be retained are urine with volume of 10 cc, feces with mass of ±40 mg, and serum with volume of 3 cc in EDTA vacutainer.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Brigitta IRV Corebime, M.D.(Paed)
Saiful Anwar General Hospital
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Target Duration
- 7 Days
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- dr. Brigitta Ida Resita Vebrianti Corebima, Sp.A(K), M.Kes, M.D.(Paed), Neonatology Division, Department of Pediatrics, Faculty of Medicine, Saiful Anwar General Hospital-University of Brawijaya
Study Record Dates
First Submitted
April 12, 2022
First Posted
April 19, 2022
Study Start
March 17, 2022
Primary Completion
May 1, 2022
Study Completion
July 1, 2022
Last Updated
April 19, 2022
Record last verified: 2022-04