COVID-19 PandemicNCT05175638
Indicators of Neuronal Insult in Newborns of COVID-19 Positive Mothers.
An observational study of COVID-19 Pandemic, run by Assiut University.
Trial summary
The coronavirus disease (COVID- 19) is now a global pandemic that was first reported in China (Wuhan) in December of 2019. Multiple placental abnormalities including fetal and maternal vascular malperfusion have been described in pregnant women infected with (COVID- 19). Read more about this study
- Who is it for?
- Ages 1 day to 2 days
- Conditions the study is for
- COVID-19 Pandemic
- What is being tested?
- Gene Expression
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Feb 2022to Oct 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 day to 2 days
- All sexes
- Child
Study population: Fifty newborn babies will be recruited from Assiut university hospital and included in this study. Thirty newborn babies delivered for COVID 19 positive mothers, and 20 newborns delivered for normal mothers will be used as control group. Informed consent will be obtained from mothers.
Who may be able to join
- The following inclusion criteria will be used (all necessary): Covid-19 positive mothers, term newborn (>37 completed gestational weeks), free from severe malformations. All infants will be examined generally, systemically and neurologically at birth for clinical assessment of HIE if present and for detection of outcome of these neonates.
Who cannot join
- free from severe malformations
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Macrophage Migration Inhibiting Factor, Enolase and Caspase-3 as Indicators of Neuronal Insult in Newborns of COVID-19 Positive Mothers.
The coronavirus disease (COVID- 19) is now a global pandemic that was first reported in China (Wuhan) in December of 2019. Multiple placental abnormalities including fetal and maternal vascular malperfusion have been described in pregnant women infected with (COVID- 19). To date, there are far fewer reports about the specific effects of (COVID- 19) in the newborns delivered for (COVID- 19) positive mothers.
Read the detailed description
COVID-19 in pregnant women has important impacts on perinatal and neonatal outcomes. Authors reported positive COVID infection in neonates born to COVID-19 positive mother.
The finding of a recent study suggested that intrauterine or intrapartum transmission is possible and recommended for further investigation. Furthermore, reports showed newborns of COVID-19 positive mother that suffered from catastrophic sequelae of hypoxic ischemic encephalopathy (HIE). These events could be attributed to COVID-19 positive status of the mother.
Neuron specific enolase is a biomarker for neuronal injury and synaptic dysfunction and have been correlated with tissue damage in different experimental models. The increased serum levels of neuron specific enolase are associated with the clinical outcome in patients with anoxic encephalopathy. Neuron specific enolase can be a candidate for a diagnostic/prognostic biomarker for neuroinflammation in COVID-19.
Additionally, the cytokines are candidate biomarkers after hypoxic-ischemic injury. Macrophage migration inhibitory factor (MIF) is a multifunctional protein that has been identified as proinflammatory cytokine and activates the production of inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon.
Macrophage migration inhibitory factor plays a central role in controlling the inflammatory and immune response, which may be of particular importance during the development of organ dysfunction in COVID-19 patients. Furthermore, it carries out the apoptosis of the cells. Significant increase of neuronal apoptosis and caspase-3 expression was demonstrated in the brain of neonatal mice exposed to hypoxic injury.
There are a limited number of studies investigating the effect of the pandemic period on the brain of the newborns. With this study, we aim to determine the impact of the COVID-19 outbreak on the neuronal functions in the neonates. The current study searches for a diagnostic/prognostic biomarker for neuroinflammation in neonate born to COVID-19 positive mothers.
- Conditions
- COVID-19 Pandemic
- Being tested
- Gene Expression
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gene ExpressionGenetic
the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers.
| Study group | Role | What they receive |
|---|---|---|
| Control | A total of 20 term newborn infants with a median gestational age of 40 weeks (range: 37-42 weeks) will be selected from the Gynecology and Obstetrics Hospital (Assiut University). All control infants should have an Apgar score of > 9 at 1, 5, and 10 minutes. Receives: Genetic: Gene Expression | |
| Study group | Thirty newborn infants born for Covid-19 positive mothers will be prospectively included in this study. The diagnosis of hypoxia will made based on Apgar score, clinical signs present during the first hours of life and acid-base status.
The following inclusion criteria will be used (all necessary): Covid-19 positive mothers, term newborn (>37 completed gestational weeks), free from severe malformations. All infants will be examined generally, systemically and neurologically at birth for clinical assessment of HIE if present and for detection of outcome of these neonates. Receives: Genetic: Gene Expression |
What is being measured
The primary outcome is the main question the study is designed to answer.
the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers.
RNA extraction Reverse Transcription polymerase chain reaction (RT-PCR) analysis:
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2022
- Study startFeb 2022 (estimated)
- Primary completionJun 2022 (estimated)
- Study completionOct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for COVID-19 PandemicStudies 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
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rasha Mohammed Ali, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05175638
- Sponsor's protocol ID
- NER
- Status last verified
- Jan 2022
- First submitted
- 1 Jan 2022
- Last updated
- 4 Jan 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Aksakal A, Kerget B, Kerget F, Askin S. Evaluation of the relationship between macrophage migration inhibitory factor level and clinical course in patients with COVID-19 pneumonia. J Med Virol. 2021 Dec;93(12):6519-6524. doi: 10.1002/jmv.27189. Epub 2021 Jul 22.
PubMed 34241898Bleilevens C, Soppert J, Hoffmann A, Breuer T, Bernhagen J, Martin L, Stiehler L, Marx G, Dreher M, Stoppe C, Simon TP. Macrophage Migration Inhibitory Factor (MIF) Plasma Concentration in Critically Ill COVID-19 Patients: A Prospective Observational Study. Diagnostics (Basel). 2021 Feb 17;11(2):332. doi: 10.3390/diagnostics11020332.
PubMed 33671433Chaparro-Huerta V, Flores-Soto ME, Merin Sigala ME, Barrera de Leon JC, Lemus-Varela ML, Torres-Mendoza BM, Beas-Zarate C. Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns. Pediatr Neonatol. 2017 Feb;58(1):70-76. doi: 10.1016/j.pedneo.2016.05.001. Epub 2016 May 31.
PubMed 27522459Deng C, Li J, Li L, Sun F, Xie J. Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice. Exp Ther Med. 2019 Jun;17(6):4517-4521. doi: 10.3892/etm.2019.7487. Epub 2019 Apr 15.
PubMed 31086583Florez-Sampedro L, Brandsma CA, de Vries M, Timens W, Bults R, Vermeulen CJ, van den Berge M, Obeidat M, Joubert P, Nickle DC, Poelarends GJ, Faiz A, Melgert BN. Genetic regulation of gene expression of MIF family members in lung tissue. Sci Rep. 2020 Oct 12;10(1):16980. doi: 10.1038/s41598-020-74121-w.
PubMed 33046825Ganti L, Serrano E, Toklu HZ. Can Neuron Specific Enolase Be a Diagnostic Biomarker for Neuronal Injury in COVID-19? Cureus. 2020 Oct 19;12(10):e11033. doi: 10.7759/cureus.11033.
PubMed 33214960Gladkevich A, Kauffman HF, Korf J. Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2004 May;28(3):559-76. doi: 10.1016/j.pnpbp.2004.01.009.
PubMed 15093964Golden TN, Simmons RA. Maternal and neonatal response to COVID-19. Am J Physiol Endocrinol Metab. 2020 Aug 1;319(2):E315-E319. doi: 10.1152/ajpendo.00287.2020. Epub 2020 Jun 23.
PubMed 32574110Haque A, Polcyn R, Matzelle D, Banik NL. New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection. Brain Sci. 2018 Feb 18;8(2):33. doi: 10.3390/brainsci8020033.
PubMed 29463007Hekimoglu B, Akturk Acar F. Effects of COVID-19 pandemic period on neonatal mortality and morbidity. Pediatr Neonatol. 2022 Jan;63(1):78-83. doi: 10.1016/j.pedneo.2021.08.019. Epub 2021 Oct 27.
PubMed 34776364Isgro MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015;867:125-43. doi: 10.1007/978-94-017-7215-0_9.
PubMed 26530364Jain P, Thakur A, Kler N, Garg P. Manifestations in Neonates Born to COVID-19 Positive Mothers. Indian J Pediatr. 2020 Aug;87(8):644. doi: 10.1007/s12098-020-03369-x. Epub 2020 Jun 5. No abstract available.
PubMed 32504454Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, Feng L. A Case Report of Neonatal 2019 Coronavirus Disease in China. Clin Infect Dis. 2020 Jul 28;71(15):853-857. doi: 10.1093/cid/ciaa225.
PubMed 32161941Wu YT, Liu J, Xu JJ, Chen YF, Yang W, Chen Y, Li C, Wang Y, Liu H, Zhang C, Jiang L, Qian ZX, Kawai A, Mol BW, Dennis CL, Xiong GP, Cheng BH, Yang J, Huang HF. Neonatal outcome in 29 pregnant women with COVID-19: A retrospective study in Wuhan, China. PLoS Med. 2020 Jul 28;17(7):e1003195. doi: 10.1371/journal.pmed.1003195. eCollection 2020 Jul.
PubMed 32722722Zeng L, Xia S, Yuan W, Yan K, Xiao F, Shao J, Zhou W. Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr. 2020 Jul 1;174(7):722-725. doi: 10.1001/jamapediatrics.2020.0878.
PubMed 32215598
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Macrophage Migration Inhibiting Factor, Enolase and Caspase-3 as Indicators of Neuronal Insult in Newborns of COVID-19 Positive Mothers.
- ClinicalTrials.gov ID
- NCT05175638
- Acronym / sponsor ID
- NER
- Conditions
- COVID-19 Pandemic
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Feb 2022 (estimated)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Oct 2022 (estimated)
- First posted
- 4 Jan 2022 (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.
The coronavirus disease (COVID- 19) is now a global pandemic that was first reported in China (Wuhan) in December of 2019. Multiple placental abnormalities including fetal and maternal vascular malperfusion have been described in pregnant women infected with (COVID- 19). To date, there are far fewer reports about the specific effects of (COVID- 19) in the newborns delivered for (COVID- 19) positive mothers.
Detailed description
COVID-19 in pregnant women has important impacts on perinatal and neonatal outcomes. Authors reported positive COVID infection in neonates born to COVID-19 positive mother.
The finding of a recent study suggested that intrauterine or intrapartum transmission is possible and recommended for further investigation. Furthermore, reports showed newborns of COVID-19 positive mother that suffered from catastrophic sequelae of hypoxic ischemic encephalopathy (HIE). These events could be attributed to COVID-19 positive status of the mother.
Neuron specific enolase is a biomarker for neuronal injury and synaptic dysfunction and have been correlated with tissue damage in different experimental models. The increased serum levels of neuron specific enolase are associated with the clinical outcome in patients with anoxic encephalopathy. Neuron specific enolase can be a candidate for a diagnostic/prognostic biomarker for neuroinflammation in COVID-19.
Additionally, the cytokines are candidate biomarkers after hypoxic-ischemic injury. Macrophage migration inhibitory factor (MIF) is a multifunctional protein that has been identified as proinflammatory cytokine and activates the production of inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon.
Macrophage migration inhibitory factor plays a central role in controlling the inflammatory and immune response, which may be of particular importance during the development of organ dysfunction in COVID-19 patients. Furthermore, it carries out the apoptosis of the cells. Significant increase of neuronal apoptosis and caspase-3 expression was demonstrated in the brain of neonatal mice exposed to hypoxic injury.
There are a limited number of studies investigating the effect of the pandemic period on the brain of the newborns. With this study, we aim to determine the impact of the COVID-19 outbreak on the neuronal functions in the neonates. The current study searches for a diagnostic/prognostic biomarker for neuroinflammation in neonate born to COVID-19 positive mothers.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | – | Genetic: Gene ExpressionA total of 20 term newborn infants with a median gestational age of 40 weeks (range: 37-42 weeks) will be selected from the Gynecology and Obstetrics Hospital (Assiut University). All control infants should have an Apgar score of > 9 at 1, 5, and 10 minutes. |
| Study group | – | Genetic: Gene ExpressionThirty newborn infants born for Covid-19 positive mothers will be prospectively included in this study. The diagnosis of hypoxia will made based on Apgar score, clinical signs present during the first hours of life and acid-base status. The following inclusion criteria will be used (all necessary): Covid-19 positive mothers, term newborn (>37 completed gestational weeks), free from severe malformations. All infants will be examined generally, systemically and neurologically at birth for clinical assessment of HIE if present and for detection of outcome of these neonates. |
Who may qualify
- Ages
- 1 day to 2 days
- Sex
- All
- Age groups
- Child
- Study population
- Fifty newborn babies will be recruited from Assiut university hospital and included in this study. Thirty newborn babies delivered for COVID 19 positive mothers, and 20 newborns delivered for normal mothers will be used as control group. Informed consent will be obtained from mothers.
Key inclusion criteria (1 listed)
- The following inclusion criteria will be used (all necessary): Covid-19 positive mothers, term newborn (>37 completed gestational weeks), free from severe malformations. All infants will be examined generally, systemically and neurologically at birth for clinical assessment of HIE if present and for detection of outcome of these neonates.
Key exclusion criteria (1 listed)
- free from severe malformations
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 |
|---|---|---|
| Gene Expressionthe expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers. | Genetic | Control, Study group |
Primary outcome
the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers.
Time frame: one month
RNA extraction Reverse Transcription polymerase chain reaction (RT-PCR) analysis:
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2022.
- Background: PubMed 34241898Aksakal A, Kerget B, Kerget F, Askin S. Evaluation of the relationship between macrophage migration inhibitory factor level and clinical course in patients with COVID-19 pneumonia. J Med Virol. 2021 Dec;93(12):6519-6524. doi: 10.1002/jmv.27189. Epub 2021 Jul 22.
- Background: PubMed 33671433Bleilevens C, Soppert J, Hoffmann A, Breuer T, Bernhagen J, Martin L, Stiehler L, Marx G, Dreher M, Stoppe C, Simon TP. Macrophage Migration Inhibitory Factor (MIF) Plasma Concentration in Critically Ill COVID-19 Patients: A Prospective Observational Study. Diagnostics (Basel). 2021 Feb 17;11(2):332. doi: 10.3390/diagnostics11020332.
- Background: PubMed 27522459Chaparro-Huerta V, Flores-Soto ME, Merin Sigala ME, Barrera de Leon JC, Lemus-Varela ML, Torres-Mendoza BM, Beas-Zarate C. Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns. Pediatr Neonatol. 2017 Feb;58(1):70-76. doi: 10.1016/j.pedneo.2016.05.001. Epub 2016 May 31.
- Background: PubMed 31086583Deng C, Li J, Li L, Sun F, Xie J. Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice. Exp Ther Med. 2019 Jun;17(6):4517-4521. doi: 10.3892/etm.2019.7487. Epub 2019 Apr 15.
- Background: PubMed 33046825Florez-Sampedro L, Brandsma CA, de Vries M, Timens W, Bults R, Vermeulen CJ, van den Berge M, Obeidat M, Joubert P, Nickle DC, Poelarends GJ, Faiz A, Melgert BN. Genetic regulation of gene expression of MIF family members in lung tissue. Sci Rep. 2020 Oct 12;10(1):16980. doi: 10.1038/s41598-020-74121-w.
- Background: PubMed 33214960Ganti L, Serrano E, Toklu HZ. Can Neuron Specific Enolase Be a Diagnostic Biomarker for Neuronal Injury in COVID-19? Cureus. 2020 Oct 19;12(10):e11033. doi: 10.7759/cureus.11033.
- Background: PubMed 15093964Gladkevich A, Kauffman HF, Korf J. Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2004 May;28(3):559-76. doi: 10.1016/j.pnpbp.2004.01.009.
- Background: PubMed 32574110Golden TN, Simmons RA. Maternal and neonatal response to COVID-19. Am J Physiol Endocrinol Metab. 2020 Aug 1;319(2):E315-E319. doi: 10.1152/ajpendo.00287.2020. Epub 2020 Jun 23.
- Background: PubMed 29463007Haque A, Polcyn R, Matzelle D, Banik NL. New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection. Brain Sci. 2018 Feb 18;8(2):33. doi: 10.3390/brainsci8020033.
- Background: PubMed 34776364Hekimoglu B, Akturk Acar F. Effects of COVID-19 pandemic period on neonatal mortality and morbidity. Pediatr Neonatol. 2022 Jan;63(1):78-83. doi: 10.1016/j.pedneo.2021.08.019. Epub 2021 Oct 27.
- Background: PubMed 26530364Isgro MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015;867:125-43. doi: 10.1007/978-94-017-7215-0_9.
- Background: PubMed 32504454Jain P, Thakur A, Kler N, Garg P. Manifestations in Neonates Born to COVID-19 Positive Mothers. Indian J Pediatr. 2020 Aug;87(8):644. doi: 10.1007/s12098-020-03369-x. Epub 2020 Jun 5. No abstract available.
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19 Pandemic, run by Assiut University.
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 1 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 4 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
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 Rasha Mohammed, MD. (01010024021, rasha.mohamed94@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers. (time frame: one month). 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 NCT05175638, which also lists 15 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 4 Jan 2022.