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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02872948
Recruitment Status : Unknown
Verified August 2016 by University Hospital, Grenoble.
Recruitment status was:  Recruiting
First Posted : August 19, 2016
Last Update Posted : August 19, 2016
Information provided by (Responsible Party):
University Hospital, Grenoble

Brief Summary:

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).

Condition or disease Intervention/treatment
Trisomy 21 Genetic: Diagnostic

Detailed Description:


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
Estimated Enrollment : 1260 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Diagnosis Accuracy of Noninvasive Screening by PCR Digital for Down Syndrom
Study Start Date : August 2015
Estimated Primary Completion Date : February 2017
Estimated Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Down Syndrome

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

Primary Outcome Measures :
  1. 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 %.

Biospecimen Retention:   Samples With DNA
It is DNA samples of 100 pregnancies including 70 euploïdes foeti and 30 trisomies 21, the diagnosis of which will beforehand have been made by the foetal karyotype.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Sample multicentrique of patients with pregnancies at high risk of T21 (risk > 1/250)

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02872948

Hospital center Recruiting
Grenoble, France, 38043
Contact: Charles Coutton    04 76 76 26 31   
Sub-Investigator: Anne Ego         
Sponsors and Collaborators
University Hospital, Grenoble

Publications of Results:
Other Publications:
Responsible Party: University Hospital, Grenoble Identifier: NCT02872948     History of Changes
Other Study ID Numbers: 38RC14.185
First Posted: August 19, 2016    Key Record Dates
Last Update Posted: August 19, 2016
Last Verified: August 2016

Keywords provided by University Hospital, Grenoble:
Non invasive prenatal testing
Down Syndrome
Digital PCR

Additional relevant MeSH terms:
Down Syndrome
Chromosome Aberrations
Pathologic Processes
Chromosome Duplication
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn