Hif-1α Covid-19NCT05158868
Effect of Post Covid-19 Hypoxia on Placenta of Normal Pregnant Women: A Possible Role of Hypoxia Inducible Factor-1α.
An observational study of Hif-1α Covid-19, run by Assiut University.
Trial summary
To study the risk of hypoxia in placenta of normal pregnant women infected with covid-19 during third trimester of pregnancy. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Hif-1α Covid-19
- What is being tested?
- HiF-1 alpha measurement
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2022to 30 Jun 2023
- 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 18 to 40 years
- Women only
- Adult
Study population: * Pregnant women who come for termination of pregnancy by CS or vaginal delivery * Gestational age is between 28-40 weeks.
Who may be able to join
- * Pregnant women who come for termination of pregnancy by CS or vaginal delivery
- Gestational age is between 28-40 weeks.
- The women will be divided into two groups:
- Covid-19 infection during 3rd trimester group (n = 25)
- Control normal pregnancy group (n = 25).
Who cannot join
- 1) Diabetes mellitus 2) Chronic hypertension 3) Preeclampsia 4) Acute or chronic infectious diseases or other chronic illness 5) Twins pregnancy 6) Anti phospholipid antibody syndrome
Trial locations and contacts
No sites are listed yet.
About this study
To study the risk of hypoxia in placenta of normal pregnant women infected with covid-19 during third trimester of pregnancy.
Read the detailed description
Hypoxaemia is an ominous sign of COVID-19, and it is usually an indicator of disease severity. An oxygen saturation above 90% is associated with better outcomes. Hypoxia indicates an imbalance of oxygen delivery to tissues and leads to compromised function.
The hypoxia-inducible factors (HIF) are considered master regulators of oxygen homeostasis and are oxygen level sensitive. HIF1a is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology.
PIGF is a proangiogenic protein and member of the vascular endothelial growth factor (VEGF) family. It is one of the key molecules in angiogenesis and vasculogenesis especially during embryogenesis and placental trophoblast is the main source of PIGF throughout the gestational period of pregnancy. It shares structural as well as amino acid sequence similarity with VEGF, but PIGF has binding affinity only for VEGF receptor1(VEGFR-1). The inter-and intramolecular cross-talk between the VEGFR-1 and VEGFR-2 is regulated by PIGF. It binds toVEGFR-1 and displaces VEGF from this receptor, which results in activation and intermolecular trans phosphorylation of VEGFR-2 thereby amplify the VEGF-induced angiogenesis.
Hypoxic environment is essential for the proliferation and differentiation of cytotrophoblast for maintenance of materno-fetal circulation at early periods of pregnancy. But its prevalence in later stages of pregnancy causes several complications that may lead to maternal and fetal morbidity and mortality.
Several researchers have proved that the overexpression of HIF-1α is associated with the increased maternal serum concentration of soluble Fms-like tyrosine kinase 1 (sFlt1) during hypoxic conditions. High circulating levels of sFlt1 exerts an antiangiogenic state that is associated with low levels of proangiogenic factors, such as PIGF, and inhibition of PIGF with its receptor VEGFR-1.
Currently, there is no information regarding the expression of HIF-1a in normal pregnant women with COVID-19 infection and its potential involvement in the placentation of this condition. Therefore, in the present work we will detect the expression of hypoxia induced factor 1a (HIF1a) and possible molecular link between the expression of HIF-1α and PIGF based on previous studies which show significant negative association between HIF-1α and PIGF expression in patients suffering from preeclampsia.
- Conditions
- Hif-1α Covid-19
- Being tested
- HiF-1 alpha measurement
- Keywords
- Hif-1α covid-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HiF-1 alpha measurementDiagnostic test
HIF1- α is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology
| Study group | Role | What they receive |
|---|---|---|
| Post covid infected group | normal pregnant women infected by covid during 3rd trimester Receives: Diagnostic Test: HiF-1 alpha measurement | |
| Control group | normal pregnant women Receives: Diagnostic Test: HiF-1 alpha measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
The mean difference between HIF-1 between study groups
real time PCR and Immunohistochemistery of Hif-1α
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2021
- Study start1 Jan 2022 (estimated)
- Primary completion30 Sep 2022 (estimated)
- Study completion30 Jun 2023 (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 Hif-1α Covid-19Studies 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
- Retrospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, FYAli, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05158868
- Sponsor's protocol ID
- Hif-1cov
- Status last verified
- Dec 2021
- First submitted
- 14 Dec 2021
- Last updated
- 15 Dec 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC; Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Apr 21;323(15):1488-1494. doi: 10.1001/jama.2020.3204.
PubMed 32125362Kashani KB. Hypoxia in COVID-19: Sign of Severity or Cause for Poor Outcomes. Mayo Clin Proc. 2020 Jun;95(6):1094-1096. doi: 10.1016/j.mayocp.2020.04.021. Epub 2020 Apr 23. No abstract available.
PubMed 32498766Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 2010 Oct 22;40(2):294-309. doi: 10.1016/j.molcel.2010.09.022.
PubMed 20965423Iyer S, Leonidas DD, Swaminathan GJ, Maglione D, Battisti M, Tucci M, Persico MG, Acharya KR. The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 A resolution. J Biol Chem. 2001 Apr 13;276(15):12153-61. doi: 10.1074/jbc.M008055200. Epub 2000 Nov 7.
PubMed 11069911Autiero M, Waltenberger J, Communi D, Kranz A, Moons L, Lambrechts D, Kroll J, Plaisance S, De Mol M, Bono F, Kliche S, Fellbrich G, Ballmer-Hofer K, Maglione D, Mayr-Beyrle U, Dewerchin M, Dombrowski S, Stanimirovic D, Van Hummelen P, Dehio C, Hicklin DJ, Persico G, Herbert JM, Communi D, Shibuya M, Collen D, Conway EM, Carmeliet P. Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med. 2003 Jul;9(7):936-43. doi: 10.1038/nm884.
PubMed 12796773FOX H. THE VILLOUS CYTOTROPHOBLAST AS AN INDEX OF PLACENTAL ISCHAEMIA. J Obstet Gynaecol Br Commonw. 1964 Dec;71:885-93. doi: 10.1111/j.1471-0528.1964.tb04375.x. No abstract available.
PubMed 14243207Kingdom JC, Kaufmann P. Oxygen and placental villous development: origins of fetal hypoxia. Placenta. 1997 Nov;18(8):613-21; discussion 623-6. doi: 10.1016/s0143-4004(97)90000-x.
PubMed 9364596Nevo O, Soleymanlou N, Wu Y, Xu J, Kingdom J, Many A, Zamudio S, Caniggia I. Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R1085-93. doi: 10.1152/ajpregu.00794.2005. Epub 2006 Apr 20.
PubMed 16627691Li H, Gu B, Zhang Y, Lewis DF, Wang Y. Hypoxia-induced increase in soluble Flt-1 production correlates with enhanced oxidative stress in trophoblast cells from the human placenta. Placenta. 2005 Feb-Mar;26(2-3):210-7. doi: 10.1016/j.placenta.2004.05.004.
PubMed 15708122
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Post Covid-19 Hypoxia on Placenta of Normal Pregnant Women: A Possible Role of Hypoxia Inducible Factor-1α.
- ClinicalTrials.gov ID
- NCT05158868
- Acronym / sponsor ID
- Hif-1cov
- Conditions
- Hif-1α Covid-19
- Keywords
- Hif-1α covid-19
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Jan 2022 (estimated)
- Primary completion
- 30 Sep 2022 (estimated)
- Study completion
- 30 Jun 2023 (estimated)
- First posted
- 15 Dec 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.
To study the risk of hypoxia in placenta of normal pregnant women infected with covid-19 during third trimester of pregnancy.
Detailed description
Hypoxaemia is an ominous sign of COVID-19, and it is usually an indicator of disease severity. An oxygen saturation above 90% is associated with better outcomes. Hypoxia indicates an imbalance of oxygen delivery to tissues and leads to compromised function.
The hypoxia-inducible factors (HIF) are considered master regulators of oxygen homeostasis and are oxygen level sensitive. HIF1a is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology.
PIGF is a proangiogenic protein and member of the vascular endothelial growth factor (VEGF) family. It is one of the key molecules in angiogenesis and vasculogenesis especially during embryogenesis and placental trophoblast is the main source of PIGF throughout the gestational period of pregnancy. It shares structural as well as amino acid sequence similarity with VEGF, but PIGF has binding affinity only for VEGF receptor1(VEGFR-1). The inter-and intramolecular cross-talk between the VEGFR-1 and VEGFR-2 is regulated by PIGF. It binds toVEGFR-1 and displaces VEGF from this receptor, which results in activation and intermolecular trans phosphorylation of VEGFR-2 thereby amplify the VEGF-induced angiogenesis.
Hypoxic environment is essential for the proliferation and differentiation of cytotrophoblast for maintenance of materno-fetal circulation at early periods of pregnancy. But its prevalence in later stages of pregnancy causes several complications that may lead to maternal and fetal morbidity and mortality.
Several researchers have proved that the overexpression of HIF-1α is associated with the increased maternal serum concentration of soluble Fms-like tyrosine kinase 1 (sFlt1) during hypoxic conditions. High circulating levels of sFlt1 exerts an antiangiogenic state that is associated with low levels of proangiogenic factors, such as PIGF, and inhibition of PIGF with its receptor VEGFR-1.
Currently, there is no information regarding the expression of HIF-1a in normal pregnant women with COVID-19 infection and its potential involvement in the placentation of this condition. Therefore, in the present work we will detect the expression of hypoxia induced factor 1a (HIF1a) and possible molecular link between the expression of HIF-1α and PIGF based on previous studies which show significant negative association between HIF-1α and PIGF expression in patients suffering from preeclampsia.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Post covid infected group | – | Diagnostic Test: HiF-1 alpha measurementnormal pregnant women infected by covid during 3rd trimester |
| Control group | – | Diagnostic Test: HiF-1 alpha measurementnormal pregnant women |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Age groups
- Adult
- Study population
- * Pregnant women who come for termination of pregnancy by CS or vaginal delivery * Gestational age is between 28-40 weeks.
Key inclusion criteria (5 listed)
- * Pregnant women who come for termination of pregnancy by CS or vaginal delivery
- Covid-19 infection during 3rd trimester group (n = 25)
- Control normal pregnancy group (n = 25).
Key exclusion criteria (1 listed)
- 1) Diabetes mellitus 2) Chronic hypertension 3) Preeclampsia 4) Acute or chronic infectious diseases or other chronic illness 5) Twins pregnancy 6) Anti phospholipid antibody syndrome
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 |
|---|---|---|
| HiF-1 alpha measurementHIF1- α is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology | Diagnostic test | Control group, Post covid infected group |
Primary outcome
The mean difference between HIF-1 between study groups
Time frame: 1 week
real time PCR and Immunohistochemistery of Hif-1α
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2021.
- Background: PubMed 32125362Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC; Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Apr 21;323(15):1488-1494. doi: 10.1001/jama.2020.3204.
- Background: PubMed 32498766Kashani KB. Hypoxia in COVID-19: Sign of Severity or Cause for Poor Outcomes. Mayo Clin Proc. 2020 Jun;95(6):1094-1096. doi: 10.1016/j.mayocp.2020.04.021. Epub 2020 Apr 23. No abstract available.
- Background: PubMed 20965423Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 2010 Oct 22;40(2):294-309. doi: 10.1016/j.molcel.2010.09.022.
- Background: PubMed 11069911Iyer S, Leonidas DD, Swaminathan GJ, Maglione D, Battisti M, Tucci M, Persico MG, Acharya KR. The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 A resolution. J Biol Chem. 2001 Apr 13;276(15):12153-61. doi: 10.1074/jbc.M008055200. Epub 2000 Nov 7.
- Background: PubMed 12796773Autiero M, Waltenberger J, Communi D, Kranz A, Moons L, Lambrechts D, Kroll J, Plaisance S, De Mol M, Bono F, Kliche S, Fellbrich G, Ballmer-Hofer K, Maglione D, Mayr-Beyrle U, Dewerchin M, Dombrowski S, Stanimirovic D, Van Hummelen P, Dehio C, Hicklin DJ, Persico G, Herbert JM, Communi D, Shibuya M, Collen D, Conway EM, Carmeliet P. Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med. 2003 Jul;9(7):936-43. doi: 10.1038/nm884.
- Background: PubMed 14243207FOX H. THE VILLOUS CYTOTROPHOBLAST AS AN INDEX OF PLACENTAL ISCHAEMIA. J Obstet Gynaecol Br Commonw. 1964 Dec;71:885-93. doi: 10.1111/j.1471-0528.1964.tb04375.x. No abstract available.
- Background: PubMed 9364596Kingdom JC, Kaufmann P. Oxygen and placental villous development: origins of fetal hypoxia. Placenta. 1997 Nov;18(8):613-21; discussion 623-6. doi: 10.1016/s0143-4004(97)90000-x.
- Background: PubMed 16627691Nevo O, Soleymanlou N, Wu Y, Xu J, Kingdom J, Many A, Zamudio S, Caniggia I. Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R1085-93. doi: 10.1152/ajpregu.00794.2005. Epub 2006 Apr 20.
- Background: PubMed 15708122Li H, Gu B, Zhang Y, Lewis DF, Wang Y. Hypoxia-induced increase in soluble Flt-1 production correlates with enhanced oxidative stress in trophoblast cells from the human placenta. Placenta. 2005 Feb-Mar;26(2-3):210-7. doi: 10.1016/j.placenta.2004.05.004.
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 Hif-1α Covid-19, 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 5 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 15 Dec 2021. 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 Walaa Ragab, MBBCh (00201099531966, fatma_y25@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The mean difference between HIF-1 between study groups (time frame: 1 week). 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 NCT05158868, 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 15 Dec 2021.