Trisomy 21 Clinical Trial
Official title:
DNAFirst: Primary Screening for Down Syndrome by Maternal Plasma DNA
This study will explore how maternal plasma circulating cell free DNA (ccfDNA) can be used as
a primary screening test for Down syndrome as part of routine clinical care in the general
pregnancy population. Plasma ccfDNA testing is currently recommended only for use as a
secondary screen for 'high-risk' women (i.e., women whose risk factors for trisomy make them
candidates for invasive testing such as chorionic villous sampling or amniocentesis). Because
most women in this 'high-risk' category are carrying unaffected fetuses, many 'unnecessary'
procedures are completed in order to identify the few women whose fetuses have a chromosomal
disorder. This creates expense, anxiety, and most importantly, loss of unaffected fetuses due
to procedure related miscarriage. Plasma DNA testing is now being used to reduce
significantly the number of women with unaffected fetuses undergoing invasive testing.
Applying such testing as a 'first-line' screen has not been well-explored, despite calls from
several clinical professional societies to do so. The investigators intent is to introduce,
under carefully monitored conditions, ccfDNA testing through Rhode Island primary prenatal
practices to the general pregnancy population. Education/orientation of prenatal care
providers, their staffs, and their patients will be carefully orchestrated, and
implementation issues identified and addressed. Telephone surveys of consented patients will
elicit responses to their understanding of the test, their satisfaction with the process, and
a comparison of their experience with serum screening in a prior pregnancy. Knowledge gained
from this study will help validate new screening paradigms involving ccfDNA testing. The
study is not designed to estimate Down syndrome detection rates with any confidence, but can
provide information on uptake rates, failure rates, screen positive rates, and the
decision-making of women with positive test results.
Maternal plasma ccfDNA testing examines fragments of maternal and fetal (placental) DNA that
are normally found in the mother's circulation. For any targeted chromosome (e.g., chromosome
21) an excess of fragments from that chromosome can strongly suggest trisomy in the fetus
(e.g., trisomy 21 or Down syndrome). This technology has been available since late 2011 but
is mainly offered in the 'high-risk setting with motivated patients, intensive education by
genetic counselors and maternal-fetal medicine professionals, and low patient volumes. As a
secondary screening test in high-risk women, this testing can reduce the frequency of
invasive procedures by 90% or more compared to conventional serum screening. Since CVS and
amniocentesis are associated with procedure-related fetal loss (an important factor among
women refusing these procedures), the use of ccfDNA testing may result in an increase in the
prenatal identification of affected fetuses in the high-risk population. However, this
technology has not been studied in the general risk group where women usually have no known
risk factors when presenting for prenatal care. The investigators' aim is to observe how
prenatal practices in Rhode Island are able to offer this technology in place of conventional
serum/ultrasound screening as early as 10 weeks of pregnancy. The investigators expect that
clinicians and office staff will be challenged by this paradigm shift, as will their
patients. The investigators intend to develop an education program for offices and introduce
the new test - DNAFirst- methodically in the Women & Infants Hospital catchment area. The
test uptake rate, reaction to its availability, and response to screen positive results will
be monitored, along with other measures relevant to implementation and test performance. The
investigators also will be surveying by telephone 100 women who have agreed to DNAFirst
testing and to being contacted to determine their understanding of and satisfaction with the
new test. Many factors may complicate this introduction and these will all need to be
addressed. For example, a screen positive result on the DNAFirst test is associated with a
much higher risk of aneuploidy(e.g., 1:2) than conventional serum screening. The DNAFirst
test is also associated with a higher rate of test failure than serum screening. The DNAFirst
testing protocol includes testing a buccal sample from the father of the baby when available.
It will be important to gauge how offices and patients perceive and accept these changes.
Secondary screening in high-risk women using ccfDNA is becoming more commonplace and is more
often covered by insurers. With expected price reductions due to improvements in sequencing
technology, it is likely that in 12-18 months, insurance coverage for ccfDNA testing will
become more routine. In such a setting expected test uptake and patient decision-making would
not be influenced by the limited insurance currently available. The investigators want to
simulate the patient's cost of ccfDNA testing to be similar to that currently encountered for
serum screening. Towards that end, Natera, Inc., a Clinical Laboratory Improvement Act
certified laboratory in San Carlos, California, has agreed to underwrite the cost of ccfDNA
testing during the study period. By identifying factors influencing patient acceptance and
understanding how patients and providers view this new paradigm compared to established serum
and sonographic screening, this project will provide unbiased evidence regarding
implementation of ccfDNA testing in a general pregnancy population that could translate into
nationwide practice.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02109770 -
Development of Non-invasive Prenatal Test for Microdeletion and Other Genetic Syndromes Based on Cell Free DNA
|
||
Completed |
NCT01925742 -
Study of the Efficacy of New Non-invasive Prenatal Tests for Screening for Fetal Trisomies Using Maternal Blood
|
N/A | |
Completed |
NCT01852708 -
Development of Non-invasive Prenatal Screening Test for Microdeletions Based on Fetal DNA Isolated From Maternal Blood
|
||
Recruiting |
NCT05527652 -
Self-Supporting Nasopharyngeal Airway (ssNPA) Treating Upper Airway Obstruction in Hypotonia
|
N/A | |
Completed |
NCT02278536 -
Multiple Gestation Study
|
||
Completed |
NCT01511458 -
Non-invasive Chromosomal Examination of Trisomy Study
|
N/A | |
Not yet recruiting |
NCT05970965 -
Periodontitis and Inflammation in Children With Down Syndrome/Trisomy 21: Study on Biological Samples
|
N/A | |
Terminated |
NCT03551418 -
Learning by Repetitive Viewing of Peer Modeling Patient Education Videos by Adults With Down Syndrome
|
N/A | |
Enrolling by invitation |
NCT03559374 -
Study of Vanadis® NIPT for Non-invasive Prenatal Screening of Trisomies (T21, T18 and T13)
|
||
Active, not recruiting |
NCT01725438 -
Non Invasive Prenatal Diagnosis of Trisomy 21 by Genetic Analysis of Circulating Fetal Cells
|
N/A | |
Active, not recruiting |
NCT05981521 -
Paternal Age and Fetal Aneuploidy
|
||
Completed |
NCT05004337 -
Verification of Risk Assignment for Whole Chromosome Using SNP-based NIPT in Vanishing Twin Pregnancies
|
||
Recruiting |
NCT02864108 -
The Crnic Institute Human Trisome Project Biobank
|
||
Completed |
NCT01931644 -
At-Home Research Study for Patients With Autoimmune, Inflammatory, Genetic, Hematological, Infectious, Neurological, CNS, Oncological, Respiratory, Metabolic Conditions
|
||
Not yet recruiting |
NCT06200519 -
Assessment of Diastolic Function During the Transitional Period and Infancy Using Serial Echocardiography
|
||
Terminated |
NCT03687866 -
Non-invasive Screening of Fetal Trisomy 21 by Digital PCR
|
||
Terminated |
NCT01545674 -
Prenatal Non-invasive Aneuploidy Test Utilizing SNPs Trial
|
||
Terminated |
NCT04747275 -
Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric Patients
|
Phase 4 | |
Completed |
NCT01821300 -
Down Syndrome Metabolic Health Study
|
||
Completed |
NCT00877292 -
A New Prenatal Blood Test for Down Syndrome
|
N/A |