Cervix; PregnancyOCCPNCT06323187
Optimization of Cervical Collections in Pregnancy
An observational study of Cervix; Pregnancy and Inherited Genetic Conditions (Diagnosis), run by Dr. Sascha Drewlo.
Trial summary
Fetal cells are not easily obtained from pregnant patients; this curtails testing to assess the health of the fetus and the mother. Currently, the only way of diagnosing fetal genetic or chromosomal abnormalities is by invasive techniques, such as chorionic villous sampling (CVS) and amniocentesis performed at 10 to… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Cervix; Pregnancy, Inherited Genetic Conditions (Diagnosis), Preeclampsia
- What is being tested?
- Cervical Sampling
- How many people
- 2,600 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2024to 28 Feb 2031
- How long will I take part?
- 9 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Women age, 18-45 who are either pregnant before 30w0d gestation or non-pregnant and not menstruating.
Who may be able to join
- Confirmed pregnancy Before 30w0d gestation for pregnant participants
- Regular menses within previous month for non-pregnant participants
- 18-45 years old
Who cannot join
- Bleeding >5 days in first trimester for pregnant participants
- Ruptured membranes for pregnant participants
- Currently menstruating for non-pregnant participants
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Fetal cells are not easily obtained from pregnant patients; this curtails testing to assess the health of the fetus and the mother. Currently, the only way of diagnosing fetal genetic or chromosomal abnormalities is by invasive techniques, such as chorionic villous sampling (CVS) and amniocentesis performed at 10 to 13 weeks and after 15 weeks of gestation, respectively. Although small, there is a risk for fetal loss with these procedures. Transcervical cell sampling (TCS), similar to a Pap smear, is a platform that meets the requirements for prenatal genetic testing (genetic testing with fetal cells obtained before birth), as well as diagnosis of maternal pregnancy complication, at a very early stage of pregnancy (as early as 5 weeks) and carries low risk for the mother and the developing fetus.
This study will examine cervical fluid collected using various noninvasive methods for TCS in pregnant women. The number of placental cells will be assessed against similarly obtained samples from nonpregnant women of reproductive age who lack cells derived from a placenta. Participating volunteers will provide written informed consent. Only standard medical procedures and approved devices will be used for collection of cervical fluid, minimizing risk to the participants and their fetuses. No test results or other benefits will be available to the participants.
Read the detailed description
The study will be non-interventional and designed for prospective sample collection and concurrent analysis. The primary endpoint will be a determination of the number of extravillous trophoblast (EVT) cells (placental cells that migrate into the reproductive tract) obtained by each device and procedure. The number of EVT cells, adjusted for purity (expression of a fetal marker, e.g., cytokeratin 7) directly determines the amount of fetal DNA that will be available for prenatal genetic testing. Secondary endpoints will include the total number of cells in the initial cervical samples and the amount of fetal DNA, RNA and/or protein isolated from the EVT cells. Where fetal DNA is obtained, we will sequence the fetal and maternal DNA for comparison of single nucleotide variant (SNV) and short tandem repeat (STR) loci to assess the purity of the fetal DNA (fetal fraction) or perform whole genome sequencing. Cell-free biomolecules present in cervical fluid will also be assessed for proteins or RNAs associated with adverse pregnancy outcomes, or cell-free fetal DNA. These parameters will be compared between the various collection methods to describe an optimal collection protocol for the purpose of analyzing fetal cells and their components.
Cohort: We will follow a group of pregnant individuals over time, collecting cervical secretions at various stages throughout pregnancy and then comparing these data to the pregnancy outcomes.
Control: We will collect cervical fluid from non-pregnant, non-menstruating women of reproductive age for comparison to the cohort participant samples. It is expected that cells or biomolecules produced by the placenta will be absent and that any signals detected would define background levels.
Descriptive: The study aims to observe and describe the properties of cervical secretions throughout pregnancy and their association with pregnancy outcomes or fetal genotype.
Establishing a registry/database: The researchers need to create a database to organize and analyze the information collected from participants, such as the properties of their cervical secretions and the outcomes of their pregnancies.
Pregnant women (N=2000) will be enrolled in this study because it is an investigation of a method for prenatal testing and the endpoint is detection of EVT cells or their products that are of fetal origin, specifically from the placenta. The age range of 18 to 45 years was chosen because this is the principal range for reproductive activity in women. Nonpregnant women (N=600) will also be enrolled to control for EVT cells in pregnant samples and determine the respective number of cells obtained in the study protocol when no EVT cells are present.
There will be no enrollment restriction based on racial or ethnic origins. The aim is to include sufficient diversity in enrollment to ensure that the benefits and burdens of research participation are distributed in an equitable manner. It is also desirable that the findings are reproducible across all racial and ethnic groups.
If the sample is taken at the time of a Pap smear, the healthcare professional will follow recommended procedures. The initial excess mucus from the canal and ectocervix, will be deposited in the collection containers provided by the PI rather than being discarded. If sample collection is conducted at a different time than the pregnancy cervical cytology, a cervical brush in addition may be obtained. Sample collection kits using devices used for Pap smears (including during pregnancy) and other methods to be investigated will be provided to the clinics. These kits will contain all devices for sample collection and shipment back to the PI. Kits will also contain a participant data sheet and instructions for sample collection. All kit materials will be coded to identify each participant. The key to the codes will be retained by each clinical site collaborator in a locked cabinet in their office so that personnel working with the PI will only have the de-identified code for each participant. To link laboratory data to clinical data, the clinical site collaborator will conduct the analysis using the key to the codes. No information from the analysis of the cervical fluid will be returned to the participant or their doctor since the study is designed to evaluate the procedures for sample procurement, not the test results.
- Conditions
- Cervix; Pregnancy, Inherited Genetic Conditions (Diagnosis), Preeclampsia, Fetal Growth Retardation
- Being tested
- Cervical Sampling
- Medical subject headings
- Disease, Pre-Eclampsia, Fetal Growth Retardation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cervical SamplingDiagnostic test
Each participant will provide a sample of fluid or mucus collected from the uterine endocervix.
| Study group | Role | What they receive |
|---|---|---|
| Pregnant Participants | Pregnant participants will be randomly assigned to provide a cervical sample using one of the devices/procedures for cervical fluid collection. Receives: Diagnostic Test: Cervical Sampling | |
| Non-Pregnant Participants | Non-pregnant participants will be randomly assigned to provide a cervical sample using one of the devices/procedures for cervical fluid collection. Receives: Diagnostic Test: Cervical Sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cellular content
The number of cells in the cervical sample that express markers for extracellular trophoblast will be determined.
Measured: 2 weeks
Cell-free content
The concentration of placental biomarkers (e.g., HLA-G, KRT7) in the cell-free supernatant of the cervical sample will be determined. Also nucleic acids derived from the placenta, including fetal DNA and placental RNAs.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2024
- Study start1 May 2024 (estimated)
- Primary completion28 Feb 2026 (estimated)
- Study completion28 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cervix; PregnancyStudies of the same condition, open and under way.
- 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
- 2,600 participants (estimated)
- Target duration
- 9 Months
Sponsor and investigators
- Lead sponsor
- Dr. Sascha Drewlo
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Sascha Drewlo, Sunnybrook Health Sciences Centre
- Investigators
- Sascha Drewlo, PhD, Principal investigator, Sunnybrook Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06323187
- Sponsor's protocol ID
- 4656
- Acronym
- OCCP
- Status last verified
- Mar 2024
- First submitted
- 14 Mar 2024
- Last updated
- 21 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is currently no plan to share IPD outside of the study team as per institutional REB guidelines. Any researchers wishing to access study IPD can contact the PI.
Publications
Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders. Obstet Gynecol. 2016 May;127(5):e108-e122. doi: 10.1097/AOG.0000000000001405.
PubMed 26938573Drewlo S, Armant DR. Quo vadis, trophoblast? Exploring the new ways of an old cell lineage. Placenta. 2017 Dec;60 Suppl 1(Suppl 1):S27-S31. doi: 10.1016/j.placenta.2017.04.021. Epub 2017 Apr 26.
PubMed 28483162Moser G, Drewlo S, Huppertz B, Armant DR. Trophoblast retrieval and isolation from the cervix: origins of cervical trophoblasts and their potential value for risk assessment of ongoing pregnancies. Hum Reprod Update. 2018 Jul 1;24(4):484-496. doi: 10.1093/humupd/dmy008.
PubMed 29608700
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Cervical Collections in Pregnancy
- ClinicalTrials.gov ID
- NCT06323187
- Acronym / sponsor ID
- OCCP / 4656
- Conditions
- Cervix; Pregnancy, Inherited Genetic Conditions (Diagnosis), Preeclampsia, Fetal Growth Retardation
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 2,600 participants (estimated)
- Lead sponsor
- Dr. Sascha DrewloUniversity, hospital or other
- Study start
- 1 May 2024 (estimated)
- Primary completion
- 28 Feb 2026 (estimated)
- Study completion
- 28 Feb 2031 (estimated)
- First posted
- 21 Mar 2024 (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.
Fetal cells are not easily obtained from pregnant patients; this curtails testing to assess the health of the fetus and the mother. Currently, the only way of diagnosing fetal genetic or chromosomal abnormalities is by invasive techniques, such as chorionic villous sampling (CVS) and amniocentesis performed at 10 to 13 weeks and after 15 weeks of gestation, respectively. Although small, there is a risk for fetal loss with these procedures. Transcervical cell sampling (TCS), similar to a Pap smear, is a platform that meets the requirements for prenatal genetic testing (genetic testing with fetal cells obtained before birth), as well as diagnosis of maternal pregnancy complication, at a very early stage of pregnancy (as early as 5 weeks) and carries low risk for the mother and the developing fetus.
This study will examine cervical fluid collected using various noninvasive methods for TCS in pregnant women. The number of placental cells will be assessed against similarly obtained samples from nonpregnant women of reproductive age who lack cells derived from a placenta. Participating volunteers will provide written informed consent. Only standard medical procedures and approved devices will be used for collection of cervical fluid, minimizing risk to the participants and their fetuses. No test results or other benefits will be available to the participants.
Detailed description
The study will be non-interventional and designed for prospective sample collection and concurrent analysis. The primary endpoint will be a determination of the number of extravillous trophoblast (EVT) cells (placental cells that migrate into the reproductive tract) obtained by each device and procedure. The number of EVT cells, adjusted for purity (expression of a fetal marker, e.g., cytokeratin 7) directly determines the amount of fetal DNA that will be available for prenatal genetic testing. Secondary endpoints will include the total number of cells in the initial cervical samples and the amount of fetal DNA, RNA and/or protein isolated from the EVT cells. Where fetal DNA is obtained, we will sequence the fetal and maternal DNA for comparison of single nucleotide variant (SNV) and short tandem repeat (STR) loci to assess the purity of the fetal DNA (fetal fraction) or perform whole genome sequencing. Cell-free biomolecules present in cervical fluid will also be assessed for proteins or RNAs associated with adverse pregnancy outcomes, or cell-free fetal DNA. These parameters will be compared between the various collection methods to describe an optimal collection protocol for the purpose of analyzing fetal cells and their components.
Cohort: We will follow a group of pregnant individuals over time, collecting cervical secretions at various stages throughout pregnancy and then comparing these data to the pregnancy outcomes.
Control: We will collect cervical fluid from non-pregnant, non-menstruating women of reproductive age for comparison to the cohort participant samples. It is expected that cells or biomolecules produced by the placenta will be absent and that any signals detected would define background levels.
Descriptive: The study aims to observe and describe the properties of cervical secretions throughout pregnancy and their association with pregnancy outcomes or fetal genotype.
Establishing a registry/database: The researchers need to create a database to organize and analyze the information collected from participants, such as the properties of their cervical secretions and the outcomes of their pregnancies.
Pregnant women (N=2000) will be enrolled in this study because it is an investigation of a method for prenatal testing and the endpoint is detection of EVT cells or their products that are of fetal origin, specifically from the placenta. The age range of 18 to 45 years was chosen because this is the principal range for reproductive activity in women. Nonpregnant women (N=600) will also be enrolled to control for EVT cells in pregnant samples and determine the respective number of cells obtained in the study protocol when no EVT cells are present.
There will be no enrollment restriction based on racial or ethnic origins. The aim is to include sufficient diversity in enrollment to ensure that the benefits and burdens of research participation are distributed in an equitable manner. It is also desirable that the findings are reproducible across all racial and ethnic groups.
If the sample is taken at the time of a Pap smear, the healthcare professional will follow recommended procedures. The initial excess mucus from the canal and ectocervix, will be deposited in the collection containers provided by the PI rather than being discarded. If sample collection is conducted at a different time than the pregnancy cervical cytology, a cervical brush in addition may be obtained. Sample collection kits using devices used for Pap smears (including during pregnancy) and other methods to be investigated will be provided to the clinics. These kits will contain all devices for sample collection and shipment back to the PI. Kits will also contain a participant data sheet and instructions for sample collection. All kit materials will be coded to identify each participant. The key to the codes will be retained by each clinical site collaborator in a locked cabinet in their office so that personnel working with the PI will only have the de-identified code for each participant. To link laboratory data to clinical data, the clinical site collaborator will conduct the analysis using the key to the codes. No information from the analysis of the cervical fluid will be returned to the participant or their doctor since the study is designed to evaluate the procedures for sample procurement, not the test results.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 9 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pregnant Participants | – | Diagnostic Test: Cervical SamplingPregnant participants will be randomly assigned to provide a cervical sample using one of the devices/procedures for cervical fluid collection. |
| Non-Pregnant Participants | – | Diagnostic Test: Cervical SamplingNon-pregnant participants will be randomly assigned to provide a cervical sample using one of the devices/procedures for cervical fluid collection. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Women age, 18-45 who are either pregnant before 30w0d gestation or non-pregnant and not menstruating.
Key inclusion criteria (3 listed)
- Confirmed pregnancy Before 30w0d gestation for pregnant participants
- Regular menses within previous month for non-pregnant participants
- 18-45 years old
Key exclusion criteria (3 listed)
- Bleeding >5 days in first trimester for pregnant participants
- Ruptured membranes for pregnant participants
- Currently menstruating for non-pregnant participants
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 |
|---|---|---|
| Cervical SamplingEach participant will provide a sample of fluid or mucus collected from the uterine endocervix. | Diagnostic test | Non-Pregnant Participants, Pregnant Participants |
Primary outcome
Cellular content
Time frame: 2 weeks
The number of cells in the cervical sample that express markers for extracellular trophoblast will be determined.
Cell-free content
Time frame: 2 weeks
The concentration of placental biomarkers (e.g., HLA-G, KRT7) in the cell-free supernatant of the cervical sample will be determined. Also nucleic acids derived from the placenta, including fetal DNA and placental RNAs.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2024.
- Background: PubMed 26938573Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders. Obstet Gynecol. 2016 May;127(5):e108-e122. doi: 10.1097/AOG.0000000000001405.
- Background: PubMed 28483162Drewlo S, Armant DR. Quo vadis, trophoblast? Exploring the new ways of an old cell lineage. Placenta. 2017 Dec;60 Suppl 1(Suppl 1):S27-S31. doi: 10.1016/j.placenta.2017.04.021. Epub 2017 Apr 26.
- Background: PubMed 29608700Moser G, Drewlo S, Huppertz B, Armant DR. Trophoblast retrieval and isolation from the cervix: origins of cervical trophoblasts and their potential value for risk assessment of ongoing pregnancies. Hum Reprod Update. 2018 Jul 1;24(4):484-496. doi: 10.1093/humupd/dmy008.
- Individual participant dataSharing planned: No. There is currently no plan to share IPD outside of the study team as per institutional REB guidelines. Any researchers wishing to access study IPD can contact the PI.
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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.
Sascha Drewlo, PhD principal investigator
Sunnybrook Research Institute
Questions about this trial
What is this clinical trial studying?
An observational study of Cervix; Pregnancy and Inherited Genetic Conditions (Diagnosis), run by Dr. Sascha Drewlo.
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 3 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: opening soon, as of the sponsor's last update on 21 Mar 2024. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sascha Drewlo, PhD (1-416-480-6100 ext. 683853, sascha.drewlo@sri.utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cellular content (time frame: 2 weeks). The study lists 2 primary outcomes in all. 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 NCT06323187, which also lists 3 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 21 Mar 2024.