Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06323187
Other study ID # 4656
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date May 1, 2024
Est. completion date February 28, 2031

Study information

Verified date March 2024
Source Sunnybrook Health Sciences Centre
Contact Sascha Drewlo, PhD
Phone 1-416-480-6100
Email sascha.drewlo@sri.utoronto.ca
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical 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 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 2600
Est. completion date February 28, 2031
Est. primary completion date February 28, 2026
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years to 45 Years
Eligibility 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 Design


Intervention

Diagnostic Test:
Cervical Sampling
Each participant will provide a sample of fluid or mucus collected from the uterine endocervix.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Dr. Sascha Drewlo

References & Publications (3)

Drewlo 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. — View Citation

Moser 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. — View Citation

Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders. Obstet Gynecol. 2016 May;127(5):e108-e122. doi: 10.1097/AOG.0000000000001405. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Cellular content The number of cells in the cervical sample that express markers for extracellular trophoblast will be determined. 2 weeks
Primary 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. 2 weeks
See also
  Status Clinical Trial Phase
Completed NCT03510286 - Validation of a PrCr Dipstick Diagnostic Test in Ghana
Recruiting NCT03313024 - Berlin-Brandenburg Pregnancy Cohort
Active, not recruiting NCT04990141 - Molecular Screening Method for Preeclampsia (PREMOM)
Completed NCT02147626 - Heart Health 4 Moms Trial to Reduce CVD Risk After Preeclampsia N/A
Not yet recruiting NCT05999851 - Multiparametric Assessment of Maternal Vascular Function in the Prediction of Hypertensive Disorders of Pregnancy N/A
Recruiting NCT02923206 - Proof-of-Concept Trial on Selective Removal of sFlt-1 in Pregnant Women With Preeclampsia Via Apheresis N/A
Completed NCT02384226 - User Testing and Feedback for a Mobile Health Program for Postpartum Women: A Pilot Study
Not yet recruiting NCT02541110 - Prediction of Preeclampsia & Other Obstetric Complications by Serum Homocysteine & Doppler N/A
Withdrawn NCT05016440 - Lisinopril for Renal Protection in Postpartum Preeclamptic Women N/A
Terminated NCT02558023 - The Treatment of Hypertension Associated With Severe Preeclampsia (PE). A Trial of Urapidil Versus Nicardipine Phase 3
Completed NCT02554604 - Identifying HDL Composition and Function in Preeclamptic and Normal Pregnancies
Completed NCT02854501 - Second Trimester Maternal Serum Homocysteine Levels and Uterine Artery Doppler for Prediction of Preeclampsia and Placentation Disorders
Recruiting NCT02247297 - Pancreatic Stone Protein (PSP) in Pregnant Women
Recruiting NCT02337049 - Preeclampsia Subtypes and Surrogate Markers of CVD Risk N/A
Completed NCT02238704 - Cornell University-Micronutrient Initiative Calcium Supplementation Study N/A
Withdrawn NCT01179542 - The Involvement of Eukaryotic Translation Initiation Factor 4E (eIF4E) in Human Placental Implantation and in the Pathological Pregnancies: Preeclampsia and IUGR N/A
Completed NCT01195441 - Prediction and Prevention of Preeclampsia by First Trimester Ultrasound N/A
Completed NCT00456118 - Study of the Role of Tissular Maternofetal Alloimmunization in Placentation Pathologies
Recruiting NCT00117546 - Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia Phase 4
Completed NCT00787241 - Platelet Count Trends in Pre-eclamptic Parturients N/A