Diagnosis Accuracy of Noninvasive Screening by PCR Digital for Down Syndrom (DIgiT21)

October 29, 2021 updated by: University Hospital, Grenoble

The main objective of this study is to estimate the intrinsic diagnostic qualities of the digital dPCR in the screening of T21 from a multicentrique sample of patients with pregnancies at high risk of T21 (risk > 1/250).

The profit expected from this technique is to propose to the encircled women a screening more successful than that of the screening combined(organized) of the 1st quarter, simple of realization and in a moderate cost. We thus propose here an original alternative(alternate) method to the exclusive, expensive and binding techniques of top-debit(-flow). The recent technical improvements and his(her,its) advantages medical - economic allow to envisage a reliable, strong and long-lasting use of the dPCR in clinical routine in the DPNI of T21 in most of the laboratories. This pilot project could serve for the later development of a study of clinical validation multicentrique of large scale(big turntable ladder).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Context

Currently, non-invasive screening test for trisomy 21 (Down syndrome) is proposed to every pregnant woman. This first trimester combined test consists of ultrasound nuchal translucency measurement, associated with different maternal serum biochemical assay and maternal age.

Since the discovery of the presence of cell-free fetal DNA in maternal plasma, the noninvasive prenatal testing (NIPT), using mainly a massive parallel sequencing (MPS) approach, has been introduced. The chromosomal origin of each sequenced plasma DNA molecule and the over- or under-representation of any chromosome can be identified by MPS in maternal plasma. The specificity and sensibility of such high-throughput techniques are excellent, close to 100 %. However, MPS remains time-consuming, very expensive (> 1000 euros per patient) and can't be used in clinical routine in most genetics laboratories worldwide.

Digital PCR represents an interesting alternative to the MPS due to its targeted approach, cost (>10x less than MPS), speed and relative simplicity allowing a clinical routine practice. However, its clinical an analytical relevance remains insufficiently demonstrated in literature data . Therefore, our main objective is to evaluate the diagnosis accuracy of noninvasive screening by PCR digital for Down syndrome.

Expected results This study will assess the sensitivity, specificity and likelihood ratio with a satisfactory accuracy. The no call rate will be also evaluated and considered as a positive test.

The optimal number of replicates (leading to a false positive rate <5%) will be determined using a ROC curve. Our hypothesis is that the sensitivity of the screening test will be upper to 95% with a false positive rate <5%.

If results are conclusive, this pilot project will be a strong argument in favor of the development of a further large scale study. It may challenge current screening strategy and allow to propose an inexpensive, fast, and accessible NIPT of trisomy 21 to a large number of laboratories in our territory.

Experimental design We will evaluate this approach on a pregnant women cohort with high risk for T21 (>1/250), prospectively recruited from three regional hospitals with a cytogenetics laboratory. We propose to preform single-blind retrospective analyses of cell free DNA of 100 pregnancies (including 70 euploid and 30 T21fetuses). Results obtained with the dPCR approach will be compared with the fetal karyotype beforehand performed. Digital PCR analyses will be performed at the Grenoble University Hospital, our team having a significant experience in digital PCR technology. Digital PCR reactions will be done on a QuantStudio™ 3D (LifeTechnologies) with the commercial high density chips etched with 20,000 consistently-sized nanoscale reaction wells. To improve the analytical sensitivity, 10 replicates will be performed for each patient.

Study Type

Observational

Enrollment (Actual)

1260

Contacts and Locations

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

Study Locations

  • France
      • Grenoble, France, 38043
        • Hospital center

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

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Sample multicentrique of patients with pregnancies at high risk of T21 (risk > 1/250)

Description

Inclusion Criteria:

  • major Patients
  • unique(only) Pregnancies
  • Screening combined(organized) by the 1st quarter of the trisomy 21 with risk > 1/250
  • Patients wishing to realize a foetal taking with diagnostic aim
  • Sent in maternity(maternity hospital) for this taking between 12 and 17 weeks of amenorrhea

Exclusion Criteria:

  • Patient refusing to participate
  • no Patient beneficiary of the Social Security or other diet
  • Private person of freedom

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
70 euploïdes foeti samples
Patients with foetus euploïde ("no sick")
Genetic: Diagnostic
30 trisomies 21 samples
Patients with foetus reached(affected) by trisomy 21 ("sick")
Genetic: Diagnostic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intrinsic diagnostic qualities of the digital dPCR in the screening of T21 from a sample multicentrique of patients with pregnancies at high risk of T21 (risk > 1/250)
Time Frame: 24 months
The main criterion is the estimation of the intrinsic qualities of the dPCR in the screening of T21. The sensibility of the screening will be favored and the reserved value will be the one giving a rate of acceptable positive forgery fixed to 5 %.
24 months

Collaborators and Investigators

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

Sponsor

University Hospital, Grenoble

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 (Actual)

August 1, 2015

Primary Completion (Actual)

February 1, 2017

Study Completion (Actual)

July 1, 2017

Study Registration Dates

First Submitted

August 16, 2016

First Submitted That Met QC Criteria

August 16, 2016

First Posted (Estimate)

August 19, 2016

Study Record Updates

Last Update Posted (Actual)

November 1, 2021

Last Update Submitted That Met QC Criteria

October 29, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC14.185

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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