Preterm LaborNCT05864066
Cyclin-dependent Kinase Inhibitor 2A (Placental Senescence Marker) on Labor-related Signals
An observational study of Preterm Labor, run by Assiut University.
Trial summary
Onset of labor in human is initiated by progesterone withdrawal. Over many decades researchers had proposed hypotheses to explain the functional withdrawal of progesterone. These hypotheses were through the sequestration of active progesterone by corticosteroid-binding globulin, a decrease in active progesterone… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Preterm Labor
- How many people
- 81 participants
- Where
- No sites listed yet
- Study dates
- Sep 2023to Feb 2025
- 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
- No healthy volunteers
- Adult
Study population: Pregnant women who will come for termination of pregnancy
Who may be able to join
- Pregnant women who will come for termination of pregnancy by caesarean section or vaginal delivery.
- Gestational age is between 28 to < 37 weeks for preterm labor and 37 to 40 weeks for term labor.
- The age range of women is between18- 40 years.
Who cannot join
- Acute or chronic infectious diseases or other chronic illness
- Autoimmune diseases
- PE complicated with Eclampsia, DIC or HELP syndrome
- Congenital anomaly of the uterus
- History of trauma
- Twins pregnancy
- Congenital anomalies of the fetus
- Fetal growth restriction
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Role of Cyclin-dependent Kinase Inhibitor 2A (P16 INK4a) (Placental Senescence Marker) on Labor-related Signals Through Progesterone Receptors Expression in Human Placenta
Onset of labor in human is initiated by progesterone withdrawal. Over many decades researchers had proposed hypotheses to explain the functional withdrawal of progesterone. These hypotheses were through the sequestration of active progesterone by corticosteroid-binding globulin, a decrease in active progesterone metabolite levels and changes in the ratio of progesterone receptor (PR) isoforms (nuclear progesterone receptors A (nPRA) and nuclear progesterone receptors B (nPRB)). Progesterone performs its action non-genomically through binding to membrane receptors and genomically via binding to nPRs. PRA is the less active or inactive form of progesterone receptors and shorter in amino acid sequence than PRB, the active form of the receptors.
Read the detailed description
Another mechanism was done through transcriptional co-activators, repressors inflammation resulting in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) mediated PR suppression. Previous study had explored that the uterine myometrium as the site of this functional withdrawal. There is also a clock that can determine the length of human pregnancy resides in the placenta and functional progesterone withdrawal likely occurs in this organ as well.
Ageing is a process that causes deterioration in function at the cellular, tissue and organ levels. Telomeres are protective caps made of nucleoprotein molecules located at the end of chromosomes and are necessary for protection against breaks at DNA ends, fusion of chromosome ends and chromosome degradation.
Telomeres are shortened with each cell division. The rate at which this occurs is accelerated by certain stressors such as oxidative stress. When telomeres reach a dangerously short length the process of cellular senescence initiates through which cells irreversibly stop growing and dividing by arresting their cell cycle and gradually ageing (becoming senescent).
Cellular senescence is a state of irreversible cell cycle arrest resulting from high levels of P16 INK4a as well as tumour 15 suppressors p53 and retinoblastoma tumour suppressor protein. Senescent cells markedly have an ability to change gene expression patterns with overexpression of anti-apoptotic Bcl-2 leading to resistance to apoptosis and in parallel increase NFκB activity results in the expression of proinflammatory cytokines and chemokines. As pregnancy comes to term, decidual cells show many features of senescence including secretion of senescence-associated secretory phenotype (SASP) factors such as interleukin-6 (IL-6). A gradual process of decidual senescence may be critical for driving the cellular and tissue changes that contribute to labor onset at term. If ageing of the placenta normally determines pregnancy duration, this means that premature placental ageing will lead to preterm labor onset.
According to World Health Organization (WHO), the American Academy of Pediatrics (AAP), and the American College of Obstetricians and Gynecologists (ACOG), preterm birth is defend as babies born alive before 37 weeks of pregnancy are completed. Each year, 15million babies are born preterm in the world. The National Center for Health Statistics of the Centers for Disease Control and Prevention generally reports data on three categories of preterm birth: overall preterm (< 37 weeks 'gestation), moderately preterm (between 32 and 36 weeks' gestation) and very preterm births (< 32 weeks' gestation). Late preterm infants are born at a gestational age between 34 weeks and less than37 weeks.
- Conditions
- Preterm Labor
- Medical subject headings
- Obstetric Labor, Premature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Women in preterm delivery with GA < 36 weeks. | |
| 2 | Women not in labor undergoing elective C-section with GA between 36 and 40 weeks. | |
| 3 | Women following spontaneous labor (without being induced) with GA between 36 and 40 weeks. |
What is being measured
The primary outcome is the main question the study is designed to answer.
P16 INK4a
1.Evaluating the role of cyclin-dependent kinase inhibitor 2A (P16 INK4a) placental senescence marker to predict time of labor.
Measured: one year
Secondary outcomes (1)
PR
2.Local effect of cyclin-dependent kinase inhibitor 2A (P16 INK4a) placental senescence marker on progesterone receptors expression in human placenta.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2023
- Study startSep 2023 (estimated)
- Primary completionSep 2024 (estimated)
- Study completionFeb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Preterm LaborStudies 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 only
- Time perspective
- Cross-sectional
- Enrolment
- 81 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fatma El-sayed Moustafa, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05864066
- Sponsor's protocol ID
- P16 INK4a and PR
- Status last verified
- May 2023
- First submitted
- 9 May 2023
- Last updated
- 18 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.
PubMed 17695343Grazul-Bilska AT, Thammasiri J, Kraisoon A, Reyaz A, Bass CS, Kaminski SL, Navanukraw C, Redmer DA. Expression of progesterone receptor protein in the ovine uterus during the estrous cycle: Effects of nutrition, arginine and FSH. Theriogenology. 2018 Mar 1;108:7-15. doi: 10.1016/j.theriogenology.2017.11.008. Epub 2017 Nov 20.
PubMed 29175682Jacobsen BM, Horwitz KB. Progesterone receptors, their isoforms and progesterone regulated transcription. Mol Cell Endocrinol. 2012 Jun 24;357(1-2):18-29. doi: 10.1016/j.mce.2011.09.016. Epub 2011 Sep 17.
PubMed 21952082Kidus F, Woldemichael K, Hiko D. Predictors of neonatal mortality in Assosa zone, Western Ethiopia: a matched case control study. BMC Pregnancy Childbirth. 2019 Mar 29;19(1):108. doi: 10.1186/s12884-019-2243-5.
PubMed 30925903Kowalik MK, Rekawiecki R, Kotwica J. Expression of membrane progestin receptors (mPRs) in the bovine corpus luteum during the estrous cycle and first trimester of pregnancy. Domest Anim Endocrinol. 2018 Apr;63:69-76. doi: 10.1016/j.domaniend.2017.12.004. Epub 2018 Jan 11.
PubMed 29413904Kumari R, Jat P. Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype. Front Cell Dev Biol. 2021 Mar 29;9:645593. doi: 10.3389/fcell.2021.645593. eCollection 2021.
PubMed 33855023Martin JA, Hamilton BE, Osterman MJK, Driscoll AK. Births: Final Data for 2018. Natl Vital Stat Rep. 2019 Nov;68(13):1-47.
PubMed 32501202Menon R, Bonney EA, Condon J, Mesiano S, Taylor RN. Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition. Hum Reprod Update. 2016 Sep;22(5):535-60. doi: 10.1093/humupd/dmw022. Epub 2016 Jun 30.
PubMed 27363410
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Cyclin-dependent Kinase Inhibitor 2A (P16 INK4a) (Placental Senescence Marker) on Labor-related Signals Through Progesterone Receptors Expression in Human Placenta
- ClinicalTrials.gov ID
- NCT05864066
- Acronym / sponsor ID
- P16 INK4a and PR
- Conditions
- Preterm Labor
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 81 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Sep 2023 (estimated)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Feb 2025 (estimated)
- First posted
- 18 May 2023 (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.
Onset of labor in human is initiated by progesterone withdrawal. Over many decades researchers had proposed hypotheses to explain the functional withdrawal of progesterone. These hypotheses were through the sequestration of active progesterone by corticosteroid-binding globulin, a decrease in active progesterone metabolite levels and changes in the ratio of progesterone receptor (PR) isoforms (nuclear progesterone receptors A (nPRA) and nuclear progesterone receptors B (nPRB)). Progesterone performs its action non-genomically through binding to membrane receptors and genomically via binding to nPRs. PRA is the less active or inactive form of progesterone receptors and shorter in amino acid sequence than PRB, the active form of the receptors.
Detailed description
Another mechanism was done through transcriptional co-activators, repressors inflammation resulting in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) mediated PR suppression. Previous study had explored that the uterine myometrium as the site of this functional withdrawal. There is also a clock that can determine the length of human pregnancy resides in the placenta and functional progesterone withdrawal likely occurs in this organ as well.
Ageing is a process that causes deterioration in function at the cellular, tissue and organ levels. Telomeres are protective caps made of nucleoprotein molecules located at the end of chromosomes and are necessary for protection against breaks at DNA ends, fusion of chromosome ends and chromosome degradation.
Telomeres are shortened with each cell division. The rate at which this occurs is accelerated by certain stressors such as oxidative stress. When telomeres reach a dangerously short length the process of cellular senescence initiates through which cells irreversibly stop growing and dividing by arresting their cell cycle and gradually ageing (becoming senescent).
Cellular senescence is a state of irreversible cell cycle arrest resulting from high levels of P16 INK4a as well as tumour 15 suppressors p53 and retinoblastoma tumour suppressor protein. Senescent cells markedly have an ability to change gene expression patterns with overexpression of anti-apoptotic Bcl-2 leading to resistance to apoptosis and in parallel increase NFκB activity results in the expression of proinflammatory cytokines and chemokines. As pregnancy comes to term, decidual cells show many features of senescence including secretion of senescence-associated secretory phenotype (SASP) factors such as interleukin-6 (IL-6). A gradual process of decidual senescence may be critical for driving the cellular and tissue changes that contribute to labor onset at term. If ageing of the placenta normally determines pregnancy duration, this means that premature placental ageing will lead to preterm labor onset.
According to World Health Organization (WHO), the American Academy of Pediatrics (AAP), and the American College of Obstetricians and Gynecologists (ACOG), preterm birth is defend as babies born alive before 37 weeks of pregnancy are completed. Each year, 15million babies are born preterm in the world. The National Center for Health Statistics of the Centers for Disease Control and Prevention generally reports data on three categories of preterm birth: overall preterm (< 37 weeks 'gestation), moderately preterm (between 32 and 36 weeks' gestation) and very preterm births (< 32 weeks' gestation). Late preterm infants are born at a gestational age between 34 weeks and less than37 weeks.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Women in preterm delivery with GA < 36 weeks. |
| 2 | – | –Women not in labor undergoing elective C-section with GA between 36 and 40 weeks. |
| 3 | – | –Women following spontaneous labor (without being induced) with GA between 36 and 40 weeks. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Pregnant women who will come for termination of pregnancy
Key inclusion criteria (3 listed)
- Pregnant women who will come for termination of pregnancy by caesarean section or vaginal delivery.
- Gestational age is between 28 to < 37 weeks for preterm labor and 37 to 40 weeks for term labor.
- The age range of women is between18- 40 years.
Key exclusion criteria (8 listed)
- Acute or chronic infectious diseases or other chronic illness
- Autoimmune diseases
- PE complicated with Eclampsia, DIC or HELP syndrome
- Congenital anomaly of the uterus
- History of trauma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
P16 INK4a
Time frame: one year
1.Evaluating the role of cyclin-dependent kinase inhibitor 2A (P16 INK4a) placental senescence marker to predict time of labor.
1 secondary outcome
PR
Time frame: one year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2023.
- Background: PubMed 17695343Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.
- Background: PubMed 29175682Grazul-Bilska AT, Thammasiri J, Kraisoon A, Reyaz A, Bass CS, Kaminski SL, Navanukraw C, Redmer DA. Expression of progesterone receptor protein in the ovine uterus during the estrous cycle: Effects of nutrition, arginine and FSH. Theriogenology. 2018 Mar 1;108:7-15. doi: 10.1016/j.theriogenology.2017.11.008. Epub 2017 Nov 20.
- Background: PubMed 21952082Jacobsen BM, Horwitz KB. Progesterone receptors, their isoforms and progesterone regulated transcription. Mol Cell Endocrinol. 2012 Jun 24;357(1-2):18-29. doi: 10.1016/j.mce.2011.09.016. Epub 2011 Sep 17.
- Background: PubMed 30925903Kidus F, Woldemichael K, Hiko D. Predictors of neonatal mortality in Assosa zone, Western Ethiopia: a matched case control study. BMC Pregnancy Childbirth. 2019 Mar 29;19(1):108. doi: 10.1186/s12884-019-2243-5.
- Background: PubMed 29413904Kowalik MK, Rekawiecki R, Kotwica J. Expression of membrane progestin receptors (mPRs) in the bovine corpus luteum during the estrous cycle and first trimester of pregnancy. Domest Anim Endocrinol. 2018 Apr;63:69-76. doi: 10.1016/j.domaniend.2017.12.004. Epub 2018 Jan 11.
- Background: PubMed 33855023Kumari R, Jat P. Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype. Front Cell Dev Biol. 2021 Mar 29;9:645593. doi: 10.3389/fcell.2021.645593. eCollection 2021.
- Background: PubMed 32501202Martin JA, Hamilton BE, Osterman MJK, Driscoll AK. Births: Final Data for 2018. Natl Vital Stat Rep. 2019 Nov;68(13):1-47.
- Background: PubMed 27363410Menon R, Bonney EA, Condon J, Mesiano S, Taylor RN. Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition. Hum Reprod Update. 2016 Sep;22(5):535-60. doi: 10.1093/humupd/dmw022. Epub 2016 Jun 30.
- 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.
Questions about this trial
What is this clinical trial studying?
An observational study of Preterm Labor, 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 3 inclusion and 8 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 18 May 2023. 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 Fatma El-Sayed Moustafa, Assistant lecturer (01094045199, fatma.taha.elsayed@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
P16 INK4a (time frame: one 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 NCT05864066, which also lists 8 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 18 May 2023.