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The Association Between LPCAT1 Genetic Polymorphism and Stress Biomarkers in Neonatal Respiratory Distress Syndrome

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ClinicalTrials.gov Identifier: NCT04947215
Recruitment Status : Recruiting
First Posted : July 1, 2021
Last Update Posted : July 1, 2021
Sponsor:
Information provided by (Responsible Party):
Ahmed Abd Elrasoul Sayed, Assiut University

Brief Summary:

Aims of the Research

Primary:

  1. Measure the levels of stress biomarkers in full and preterm neonates with normal and complicated pregnancies and to study the influence of delivery mode on their cord blood concentrations.
  2. Test the association between LPCAT1 genetic polymorphism and the levels of these biomarkers in neonates suffering from RDS.
  3. Study the relation between LPCAT1 genetic polymorphism and the risk/severity of neonatal respiratory distress syndrome.

Secondary:

1) Help understanding the possible etiology and pathogenesis of neonatal RDS. 2) Help the possibility of early detection, diagnosis and management.

3) Help to decrease mortality and morbidity in selective cases. 4) Understand the individual variability in the susceptibility to development of pulmonary pathologies.


Condition or disease Intervention/treatment
Neonatal Respiratory Distress Diagnostic Test: stress biomarkers

Detailed Description:

Neonatal respiratory distress syndrome (RDS) is caused by lung immaturity and deficiency of lung surfactant and dysfunction in preterm newborns . Surfactant is produced by type II pneumocyte that forms a bilayer of lipid over the inner surface of the alveoli. Surfactant deficiency and dysfunction lead to increased alveolar surface tension, which results in alveolar collapse and decreased lung aeration . Respiratory distress syndrome is one of the main causes of neonatal mortality . The risk of RDS increases with decreasing gestational age (GA). The incidence of RDS was estimated to be 90% in preterm neonates (GA 28 weeks or below) and to be 9% in full term neonates born at ≥38 weeks' gestation. Early diagnosis is very essential to optimize the treatment of infants with RDS.

Pathogenesis The primary cause of RDS is deficiency and/or dysfunction of surfactant which is a lipoprotein complex and is vital for normal lung function. Surfactant is synthesized, stored, and secreted by the alveolar type II cells and is primarily composed of phospholipids, which constitute 80-85% of the total mass. The remaining components of surfactant includes neutral lipids (5%-10%) and proteins (10%) . Phosphatidylcholine (PC), the most abundant phospholipid species in surfactant, constitutes 80% of the total phospholipids. There are three key enzymes involved in the PC synthesis: Lysophospholipid acyltransferase (LPCAT1, Gene ID 79888), Cholinephosphotransferase (CHPT1, Gene ID 56994) and Cholinephosphate cytidylyltransferase (PCYT1B, CPCT, Gene ID 9468). LPCAT1 is the most important enzyme in biogenesis and a key enzyme in surfactant production . LPCAT1 composed of 18 exons and is located on chromosome 5p15.33. The study of the genetic polymorphisms of surfactant-lipids related gene provides significant data about individual variability in the susceptibility to development of respiratory distress syndrome.

Neonatal stress biomarkers such as cardiac troponin (CTn) T, CTnI, NT-Terminal-pro-Brain Natriuretic Peptide (NT-pro-BNP), copeptin, and high sensitivity C-reactive protein (hs-CRP)have been considered as an indicator of perinatal asphyxia. Troponin is an inhibitory protein complex located on the actin filament in all striated muscle and consists of three subunits: T, C, and I. The asphyxiated neonate has elevated levels of cardiac troponin I (cTnI). cTnI is thought to be also an indicator of perinatal asphyxia . Neonates born after complicated delivery had significantly higher values of CTnT, CTnI and Copeptin than those born after uncomplicated delivery. The gender influence on copeptin releases . The gestational age, birth weight and duration of active labor, and membrane rupture have significant effect on hs-CRP levels.

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Study Type : Observational
Estimated Enrollment : 160 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: The Association Between LPCAT1 Genetic Polymorphism and Stress Biomarkers in Neonatal Respiratory Distress Syndrome
Estimated Study Start Date : August 1, 2021
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : July 31, 2022


Group/Cohort Intervention/treatment
Cases group
It includes 100 neonates who are admitted in the neonatal intensive care unit in Assiut University children hospital suffering from RDS. The cases will be subdivided into subgroups according to1. Full term or preterm, 2. Type of pregnancy (normal or complicated), 3. Mode of delivery, and 4. LPCAT1 genetic polymorphism.
Diagnostic Test: stress biomarkers
used to estimate the reference values of putative biomarkers of birth stress such asCTnT, CTnI, copeptin, NT-proBNP and hs-CRP in the cord blood of full term neonates

control group
include 60 neonates without RDS.
Diagnostic Test: stress biomarkers
used to estimate the reference values of putative biomarkers of birth stress such asCTnT, CTnI, copeptin, NT-proBNP and hs-CRP in the cord blood of full term neonates




Primary Outcome Measures :
  1. LPCAT1 genetic polymorphism [ Time Frame: "1 year" ]
    The LPCAT1genetic polymorphism work will be performed using an improved multiplex ligation detection reaction (iMLDR) technique .Genomic DNA from patients will be extracted from peripheral blood by DNA mini extraction kit.


Secondary Outcome Measures :
  1. The electrochemiluminescence immunoassay ECLIA: [ Time Frame: "1 month" ]
    This method will be used to estimate the reference values of putative biomarkers of birth stress CTnT in the cord blood of full term neonates

  2. The electrochemiluminescence immunoassay ECLIA [ Time Frame: "2 month" ]
    This method will be used to estimate the reference values of putative biomarkers of birth stress hs-CRP in the cord blood of full term neonates


Biospecimen Retention:   Samples With DNA
  • Two and half mL of cord blood will be obtained from umbilical cord artery immediately after delivery on tube after centrifugation the serum will be separated and frozen at -70oC until analysis of stress biomarker.
  • Two and half mL of peripheral blood will be obtained from neonates on EDTA tube that was preserved at -70 C for DNA extraction for genetics work.


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Ages Eligible for Study:   up to 1 Month   (Child)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
A case-control study
Criteria

Inclusion Criteria:

  • neonates who are admitted in the neonatal intensive care unit in Assiut University children hospital suffering from RDS.

Exclusion Criteria:

  • The newborn will be excluded from the study when his/her parents refuses to participate or when the neonate presented with one or more of the following:

    1. Multiple congenital anomalies
    2. Severe infection
    3. Inherited metabolic disorders
    4. Any systemic disorder (hepatic, renal, cardiovascular, and endocrinal, ...etc)
    5. Malignancies
    6. Hypoxic Ischemic Encephalopathy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04947215


Contacts
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Contact: Ahmed AEL sayed, Master +201063656071 drahmedabdo1986@gmail.com
Contact: Khalid Mo Mohany, MD +201146007069 khalidmohany@aun.edu.eg

Locations
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Egypt
Assiut university Recruiting
Assiut, Egypt
Assiut University Recruiting
Assiut, Egypt
Contact: Assuit university         
Sponsors and Collaborators
Assiut University
Publications:

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Responsible Party: Ahmed Abd Elrasoul Sayed, clinical pharmacist, Assiut University
ClinicalTrials.gov Identifier: NCT04947215    
Other Study ID Numbers: Neonatal RDS
First Posted: July 1, 2021    Key Record Dates
Last Update Posted: July 1, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ahmed Abd Elrasoul Sayed, Assiut University:
LPCAT 1
Additional relevant MeSH terms:
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Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Hyaline Membrane Disease
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases