Optimization of Cervical Collections in Pregnancy (OCCP)

March 14, 2024 updated by: Dr. Sascha Drewlo

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

2600

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Women age, 18-45 who are either pregnant before 30w0d gestation or non-pregnant and not menstruating.

Description

Inclusion Criteria:

  • Confirmed pregnancy Before 30w0d gestation for pregnant participants
  • Regular menses within previous month for non-pregnant participants
  • 18-45 years old

Exclusion Criteria:

  • Bleeding >5 days in first trimester for pregnant participants
  • Ruptured membranes for pregnant participants
  • Currently menstruating for non-pregnant participants

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pregnant Participants
Pregnant participants will be randomly assigned to provide a cervical sample using one of the devices/procedures for cervical fluid collection.
Diagnostic test: Cervical Sampling
Each participant will provide a sample of fluid or mucus collected from the uterine endocervix.
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.
Diagnostic test: Cervical Sampling
Each participant will provide a sample of fluid or mucus collected from the uterine endocervix.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cellular content
Time Frame: 2 weeks
The number of cells in the cervical sample that express markers for extracellular trophoblast will be determined.
2 weeks
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.
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dr. Sascha Drewlo

Investigators

  • Principal Investigator: Sascha Drewlo, PhD, Sunnybrook Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Estimated)

February 28, 2026

Study Completion (Estimated)

February 28, 2031

Study Registration Dates

First Submitted

March 14, 2024

First Submitted That Met QC Criteria

March 14, 2024

First Posted (Actual)

March 21, 2024

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 14, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4656

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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