Neonatal Respiratory DistressNCT04947215
The Association Between LPCAT1 Genetic Polymorphism and Stress Biomarkers in Neonatal Respiratory Distress Syndrome
An observational study of Neonatal Respiratory Distress, run by Assiut University at 2 sites in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 hour to 1 month
- Conditions the study is for
- Neonatal Respiratory Distress
- What is being tested?
- stress biomarkers
- How many people
- 160 participants
- Where
- 2 sitesEgypt
- Study dates
- 1 Aug 2021to 31 Jul 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 1 month
- All sexes
- Child
Study population: A case-control study
Who may be able to join
- neonates who are admitted in the neonatal intensive care unit in Assiut University children hospital suffering from RDS.
Who cannot join
- 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:
- Multiple congenital anomalies
- Severe infection
- Inherited metabolic disorders
- Any systemic disorder (hepatic, renal, cardiovascular, and endocrinal, ...etc)
- Malignancies
- Hypoxic Ischemic Encephalopathy
Trial locations and contacts
2 sites in 1 country.
Egypt2 sites, 2 recruiting
- Recruiting
Assiut university
Asyut
- Recruiting
Assiut University
Asyut
Assuit university
About this study
Aims of the Research
Primary:
Read more
- 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.
- Test the association between LPCAT1 genetic polymorphism and the levels of these biomarkers in neonates suffering from RDS.
- Study the relation between LPCAT1 genetic polymorphism and the risk/severity of neonatal respiratory distress syndrome.
Secondary:
- Help understanding the possible etiology and pathogenesis of neonatal RDS. 2) Help the possibility of early detection, diagnosis and management.
- Help to decrease mortality and morbidity in selective cases. 4) Understand the individual variability in the susceptibility to development of pulmonary pathologies.
Read the 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.
- Conditions
- Neonatal Respiratory Distress
- Being tested
- stress biomarkers
- Keywords
- LPCAT 1
- Medical subject headings
- Pulmonary Atelectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stress biomarkersDiagnostic test
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: stress biomarkers | |
| control group | include 60 neonates without RDS. Receives: Diagnostic Test: stress biomarkers |
What is being measured
The primary outcome is the main question the study is designed to answer.
LPCAT1 genetic polymorphism
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.
Measured: "1 year"
Secondary outcomes (2)
The electrochemiluminescence immunoassay ECLIA:
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
Measured: "1 month"
The electrochemiluminescence immunoassay ECLIA
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
Measured: "2 month"
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2021
- Study start1 Aug 2021 (estimated)
- Primary completion30 Jun 2022 (estimated)
- Study completion31 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Neonatal Respiratory DistressStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmed Abd Elrasoul Sayed, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04947215
- Sponsor's protocol ID
- Neonatal RDS
- Status last verified
- Jun 2021
- First submitted
- 14 Jun 2021
- Last updated
- 1 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
De Bisschop B, Derriks F, Cools F. Early Predictors for INtubation-SURfactant-Extubation Failure in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Systematic Review. Neonatology. 2020;117(1):33-45. doi: 10.1159/000501654. Epub 2019 Aug 22.
PubMed 31437836Ma H, Yan W, Liu J. Diagnostic value of lung ultrasound for neonatal respiratory distress syndrome: a meta-analysis and systematic review. Med Ultrason. 2020 Sep 5;22(3):325-333. doi: 10.11152/mu-2485. Epub 2020 Apr 15.
PubMed 32399541Alemu AY, Belay GM, Berhanu M, Minuye B. Determinants of neonatal mortality at neonatal intensive care unit in Northeast Ethiopia: unmatched case-control study. Trop Med Health. 2020 Jun 3;48:40. doi: 10.1186/s41182-020-00232-9. eCollection 2020.
PubMed 32514229Kim M, Porras-Gomez M, Leal C. Graphene-based sensing of oxygen transport through pulmonary membranes. Nat Commun. 2020 Feb 27;11(1):1103. doi: 10.1038/s41467-020-14825-9.
PubMed 32107376Lin S, Ikegami M, Moon C, Naren AP, Shannon JM. Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) Specifically Interacts with Phospholipid Transfer Protein StarD10 to Facilitate Surfactant Phospholipid Trafficking in Alveolar Type II Cells. J Biol Chem. 2015 Jul 24;290(30):18559-74. doi: 10.1074/jbc.M115.666701. Epub 2015 Jun 5.
PubMed 26048993Shen W, Kuang P, Wang B, Zeng Q, Chen C, Lin X. Genetic Polymorphisms of LPCAT1, CHPT1 and PCYT1B and Risk of Neonatal Respiratory Distress Syndrome among a Chinese Han Population. Pediatr Neonatol. 2020 Jun;61(3):318-324. doi: 10.1016/j.pedneo.2019.12.012. Epub 2020 Jan 3.
PubMed 31964590Rouatbi H, Zigabe S, Gkiougki E, Vranken L, Van Linthout C, Seghaye MC. Biomarkers of neonatal stress assessment: A prospective study. Early Hum Dev. 2019 Oct;137:104826. doi: 10.1016/j.earlhumdev.2019.104826. Epub 2019 Jul 27.
PubMed 31362253Evers KS, Wellmann S. Arginine Vasopressin and Copeptin in Perinatology. Front Pediatr. 2016 Aug 2;4:75. doi: 10.3389/fped.2016.00075. eCollection 2016.
PubMed 27532032Ishibashi M, Takemura Y, Ishida H, Watanabe K, Kawai T. C-reactive protein kinetics in newborns: application of a high-sensitivity analytic method in its determination. Clin Chem. 2002 Jul;48(7):1103-6. No abstract available.
PubMed 12089183
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Association Between LPCAT1 Genetic Polymorphism and Stress Biomarkers in Neonatal Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT04947215
- Acronym / sponsor ID
- Neonatal RDS
- Conditions
- Neonatal Respiratory Distress
- Keywords
- LPCAT 1
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Aug 2021 (estimated)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 31 Jul 2022 (estimated)
- First posted
- 1 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aims of the Research
Primary:
- 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.
- Test the association between LPCAT1 genetic polymorphism and the levels of these biomarkers in neonates suffering from RDS.
- Study the relation between LPCAT1 genetic polymorphism and the risk/severity of neonatal respiratory distress syndrome.
Secondary:
- Help understanding the possible etiology and pathogenesis of neonatal RDS. 2) Help the possibility of early detection, diagnosis and management.
- Help to decrease mortality and morbidity in selective cases. 4) Understand the individual variability in the susceptibility to development of pulmonary pathologies.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases group | – | Diagnostic Test: stress biomarkersIt 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. |
| control group | – | Diagnostic Test: stress biomarkersinclude 60 neonates without RDS. |
Who may qualify
- Ages
- 1 hour to 1 month
- Sex
- All
- Age groups
- Child
- Study population
- A case-control study
Key inclusion criteria (1 listed)
- neonates who are admitted in the neonatal intensive care unit in Assiut University children hospital suffering from RDS.
Key exclusion criteria (7 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| stress biomarkersused 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 | Diagnostic test | Cases group, control group |
Primary outcome
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.
2 secondary outcomes
The electrochemiluminescence immunoassay ECLIA:
Time frame: "1 month"
The electrochemiluminescence immunoassay ECLIA
Time frame: "2 month"
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2021.
- Background: PubMed 31437836De Bisschop B, Derriks F, Cools F. Early Predictors for INtubation-SURfactant-Extubation Failure in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Systematic Review. Neonatology. 2020;117(1):33-45. doi: 10.1159/000501654. Epub 2019 Aug 22.
- Background: PubMed 32399541Ma H, Yan W, Liu J. Diagnostic value of lung ultrasound for neonatal respiratory distress syndrome: a meta-analysis and systematic review. Med Ultrason. 2020 Sep 5;22(3):325-333. doi: 10.11152/mu-2485. Epub 2020 Apr 15.
- Background: PubMed 32514229Alemu AY, Belay GM, Berhanu M, Minuye B. Determinants of neonatal mortality at neonatal intensive care unit in Northeast Ethiopia: unmatched case-control study. Trop Med Health. 2020 Jun 3;48:40. doi: 10.1186/s41182-020-00232-9. eCollection 2020.
- Background: PubMed 32107376Kim M, Porras-Gomez M, Leal C. Graphene-based sensing of oxygen transport through pulmonary membranes. Nat Commun. 2020 Feb 27;11(1):1103. doi: 10.1038/s41467-020-14825-9.
- Background: PubMed 26048993Lin S, Ikegami M, Moon C, Naren AP, Shannon JM. Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) Specifically Interacts with Phospholipid Transfer Protein StarD10 to Facilitate Surfactant Phospholipid Trafficking in Alveolar Type II Cells. J Biol Chem. 2015 Jul 24;290(30):18559-74. doi: 10.1074/jbc.M115.666701. Epub 2015 Jun 5.
- Background: PubMed 31964590Shen W, Kuang P, Wang B, Zeng Q, Chen C, Lin X. Genetic Polymorphisms of LPCAT1, CHPT1 and PCYT1B and Risk of Neonatal Respiratory Distress Syndrome among a Chinese Han Population. Pediatr Neonatol. 2020 Jun;61(3):318-324. doi: 10.1016/j.pedneo.2019.12.012. Epub 2020 Jan 3.
- Background: PubMed 31362253Rouatbi H, Zigabe S, Gkiougki E, Vranken L, Van Linthout C, Seghaye MC. Biomarkers of neonatal stress assessment: A prospective study. Early Hum Dev. 2019 Oct;137:104826. doi: 10.1016/j.earlhumdev.2019.104826. Epub 2019 Jul 27.
- Background: PubMed 27532032Evers KS, Wellmann S. Arginine Vasopressin and Copeptin in Perinatology. Front Pediatr. 2016 Aug 2;4:75. doi: 10.3389/fped.2016.00075. eCollection 2016.
- Background: PubMed 12089183Ishibashi M, Takemura Y, Ishida H, Watanabe K, Kawai T. C-reactive protein kinetics in newborns: application of a high-sensitivity analytic method in its determination. Clin Chem. 2002 Jul;48(7):1103-6. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neonatal Respiratory Distress, run by Assiut University at 2 sites in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ahmed AEL sayed, Master (+201063656071, drahmedabdo1986@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LPCAT1 genetic polymorphism (time frame: "1 year"). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04947215, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2021.