- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04285814
Technology Development for Noninvasive Prenatal Genetic Diagnosis Using Whole Fetal Cells From Maternal Peripheral Blood
Study Overview
Status
Intervention / Treatment
Detailed Description
This is a revision to a project entitled "Prenatal Genetic Diagnosis by Genomic Sequencing: A Prospective Evaluation." This study proposes to test the utility and accuracy of a new form of cell-based noninvasive prenatal testing (NIPT), here called noninvasive Single Fetal Cell (SFC) testing. After many years of development work, the researchers published evidence for the feasibility of SFC testing in 2016. Extensive recent preliminary data show considerable improvements in SFC testing. Current forms of cell-free NIPT testing do not provide reliable detection of medium to smaller size deletions and duplications that cause a variety of genetic disabilities. Preliminary data indicate that SFC testing using fetal trophoblasts from mother's blood can detect aneuploidy and subchromosomal deletions and emphasize the importance of analyzing single cells, since some fetal cells are apoptotic and some are in S phase of the cell cycle replicating their DNA. Both apoptosis and S phase interfere with copy number analysis in differing ways, and pooling cells prior to barcoding individual cells results in loss of data quality. Preliminary data from two pilot validation studies demonstrate that reliable data can be collected on the large majority of patients, although data on this point would be greatly expanded by this project.
Preliminary data show very robust detection of all aneuploidies and clear definition of genomic deletions as small as 1 Mb and duplications as small as 1.5 Mb. The first aim is to perform blinded SFC testing on 50 cases per year with congenital anomalies with abnormal karyotype or chromosomal microarray (CMA) and 50 cases per year with congenital anomalies and normal CMA. This will provide a direct measure of success rate and the false positive and false negative rates for SFC testing compared to CMA. The second aim will be to use the WGA products and frozen unamplified cells available from aim 1 to further improve SFC testing to include targeted detection of inherited or de novo pathogenic point mutations in the cases undergoing WGS as part of the parent grant, confirmation of very small CNVs detected by WGS, restudy of false positive or false negative results from aim 1, and in the future could attempt to perform genome wide detection of de novo mutations. Capitalizing on the resources available through the parent grant, there is the opportunity to test whether SFC testing has the potential to transform genetic prenatal diagnosis so that all genetic changes, whether CNV or point mutation, and whether inherited or de novo, could be detected even in low risk pregnancies.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Ronald Wapner, MD
- Phone Number: 212-305-1521
- Email: rw2191@cumc.columbia.edu
Study Contact Backup
- Name: Jessica Giordano, MS
- Phone Number: 516-521-5604
- Email: jlg2197@cumc.columbia.edu
Study Locations
-
-
New York
-
New York, New York, United States, 10032
- Recruiting
- Columbia University
-
Contact:
- Jessica Giordano, MS
- Phone Number: 516-521-5604
- Email: jlg2197@cumc.columbia.edu
-
Contact:
- Ronald Wapner, MD
- Phone Number: 212-305-5191
- Email: rw2191@columbia.edu
-
Principal Investigator:
- Ronald Wapner, MD
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- Baylor College of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Have already had a CVS or amniocentesis (blood sample collected >= 7 days after procedure).
- Have already received an abnormal (case) or normal (control) CMA/karyotype/FISH result from the CVS or amniocentesis.
Exclusion Criteria:
- Unavailability of maternal blood sample at least 7 days post-procedure.
- Language barrier (non-English or Spanish speaking and no adequate interpreter)
- Maternal age of less than 18 years
- Higher order multiple pregnancy (triplet or greater)
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Normal CMA
150 women whose blood samples will be drawn for WFC testing who previously had a CMA performed with normal results.
|
Performing WFC testing on blood specimens.
|
Abnormal CMA
150 women whose blood samples will be drawn for WFC testing who previously had a CMA performed with abnormal results.
|
Performing WFC testing on blood specimens.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Using a population of pregnancies with abnormal and normal karyotypes and CMAs, determine the false positive, false negative, true positive, and true negative rates of WFC testing.
Time Frame: 3 years
|
3 years
|
Determine the technical success rate for WFC testing including number of scorable cells for each sample.
Time Frame: 3 years
|
3 years
|
Determine the level of resolution for detecting deletions/duplications by WFC testing based on "spiked in" samples of known CNVs and on analysis of naturally occurring CNVs in fetal cells.
Time Frame: 3 years
|
3 years
|
Determine capability and success rate for genotyping single gene mutations including de novo and inherited single gene mutations and benign SNPs.
Time Frame: 3 years
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Evaluate WFC testing results according to gestational age at testing, specific anomalies, maternal weight, and multiple gestations.
Time Frame: 3 years
|
3 years
|
Determine whether cells are more frequent in pregnancies resulting in adverse pregnancy outcomes including preeclampsia.
Time Frame: 3 years
|
3 years
|
Improve methods for genotyping single cells including ability to perform genotyping and genome-wide copy number analysis on the same cell.
Time Frame: 3 years
|
3 years
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AAAS9107
- 3R01HD055651 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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