Generalized Neonatal Screening of Severe Combined Immunodeficiencies

NCT ID: NCT02244450

Last Updated: 2018-07-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

190539 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2018-04-28

Brief Summary

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Severe combined Immunodeficiencies ( SCID ) are a group of inherited diseases of the immune system by characterised profound abnormalities of T cell development . Infants with SCID require prompt clinical response to Prevent life -threatening infection and studies show significantly improved survival in babies Diagnosed at birth as a result of previous family history . SCID follows criteria for population -based newborn screening since it is asymptomatic at birth and fatal within the first year of life, the confirmation of the disease is easy, there is a curative treatment , and it is known that early stem cell transplantation improves survival . Quantification of TRECs (T- cell receptor excision circles ) in DNA extracted from Guthrie samples is a sensitive screening test for Specific and SCID .

The investigators propose in this study to perform a neonatal screening of SCID , in a population of 200,000 babies over a period of two years .

The investigators propose to study the clinical utility and cost effectiveness ratio, and SCID screening to demonstrate that could result in a broad benefit to Individuals detected , making screening relatively cost-effective in spite of the low incidence of the disease .

Detailed Description

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The project proposes to study the feasibility and cost-effectiveness ratio ( time management and life expectancy to 10 years) of generalized neonatal screening for SCID children by offering this screening to 200 000 children (100 000 children per year) over the entire territory. Prospective control group consists of children diagnosed with SCID out of 700,000 annual births who do not benefit from screening.

The protocol will be leant against the existing newborn screening , that is to say two more drops of blood are placed on a second Guthrie card when current screening (72 hours of life ) is performed after parents' information and consent. Eleven newborn screening regional associations will be involved with the inclusion of children in about 50 maternity hospitals. The card drawn for the protocol will follow the usual network except that the test for quantifying TRECs will be realized in two laboratories instead of eleven laboratories assigned to RA . Investigative Regional Associations (RAs) represent nearly 600,000 births / year and the amount of 200,000 children will be achieved in two years (duration of inclusion) . All children born in the participating maternity may be included if they meet the inclusion criteria. The result of the screening test for SCID will be available within 21 days after birth, provided that there is no need to request a new sample.

At each of eleven RA is associated a pediatrician referent for immune deficiencies, member of the french reference center (CEREDIH) and who will be responsible to call the parents, offer them a consultation and further exploration if the result of screening is assumed positive.

Analysis of cards from 200,000 children will give the following information:

* Number of children with a presumptive positive screening , requiring a call by the referent pediatrician, consultation and exploration of lymphocyte subpopulations
* Number of children with a negative screening
* Number of children with an inconclusive screening (lack of TRECs and lack of amplification of the reference gene) and requiring a new card,

A micro- costing study will be conducted to assess the cost of testing .

This group of 200,000 children is the experimental group to assess the cost of screening , acceptability by parents (participation rate), the recall rate for abnormal or inconclusive result, the rate of follow-up time for results , the incidence of disease . It will also allow to calculate the specificity of the method .

At the end of the inclusions, the vital status at 18 months with cause of death will be sought for the 200 000 children included , with the CESP ( Centre de Recherche en Epidemiologie et Santé des Populations) via RNIPP (Répertoire National d'Identification des Personnes Physiques) and CepiDc ( Centre d'Epidémiologie sur les causes médicales de décès) . This will establish whether there are SCID in this population which were not detected at birth. Furthermore, the investigators include in the study SCID children diagnosed without screening by pediatricians local referents DIP (including Necker main transplant center) . This will enable to approach the sensitivity of the method . All these data allow the calculation of the predictive values of the test.

In this experimental group will be isolated a group of individuals who screened positive and diagnosed as true SCID . Clinical data for these patients will be collected in an electronic CRF ( CRF ) by the pediatrician referral protocol (Dr Thomas C ) , including:

* The dates and results of explorations : lymphocyte subpopulations , blood count, determination of immunoglobulin levels
* The diagnosis made with identification of the genetic defect
* The date of care before curative treatment ( protected area isolation , anti -infective drugs )
* , Bacterial , fungal anti -viral treatments , and other
* The date of transplant, type of transplant or other treatment ... ...

Conditions

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Severe Combined Immunodeficiency, Atypical

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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Screened patients

SCID screening: more drops of blood are placed on a second Guthrie card when current screening (72 hours of life ) is performed after parents' information and consent. The card drawn for the protocol will follow the usual network except that the test for quantifying TRECs will be realized to determine the presence of SCID.

Group Type EXPERIMENTAL

SCID screening

Intervention Type BIOLOGICAL

Control group

SCID children diagnosed without screening by pediatricians local referents DIP

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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SCID screening

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Screening Group: Newborn on day 3 of birth (premature and non premature)
* Control group: Patients diagnosed with SCID without screening at participating centers

Exclusion Criteria

* Lack of parental consent
* Children whose parents are adults under guardianship,
* Children without health insurance, for the screening group:
* The early exit of the child from the maternity hospital
Minimum Eligible Age

3 Days

Maximum Eligible Age

18 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Nantes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Caroline THOMAS, MD

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Marie AUDRAIN, MD

Role: STUDY_DIRECTOR

Nantes University Hospital

Sophie MIRALLIE

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

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Angers Private Hospital Clinique de l'Anjou

Angers, , France

Site Status

Angers University Hospital

Angers, , France

Site Status

Argenteuil Hospital

Argenteuil, , France

Site Status

Aulnay-sous-Bois Hospital CHI Robert Ballanger

Aulnay-sous-Bois, , France

Site Status

Bordeaux Maison de Santé Protestante Bordeaux Bagatelle

Bordeaux, , France

Site Status

Bordeaux Private Hospital Polyclinique Bordeuax Nord Aquitaine

Bordeaux, , France

Site Status

Bordeaux University Hospital

Bordeaux, , France

Site Status

Corbeil Essonnes Hospital Sud Francilien

Corbeil-Essonnes, , France

Site Status

Créteil Hospital

Créteil, , France

Site Status

Dijon University Hospital

Dijon, , France

Site Status

Grenoble University Hospital

Grenoble, , France

Site Status

Le Blanc Mesnil Private Hospital

Le Blanc-Mesnil, , France

Site Status

Lens Hospital

Lens, , France

Site Status

Libourne Maternity Hospital

Libourne, , France

Site Status

Lille University Hospital

Lille, , France

Site Status

Lormont Maternity Hospital Rive Droite

Lormont, , France

Site Status

Lyon Maternity Hospital

Lyon, , France

Site Status

Lyon University Hospital

Lyon, , France

Site Status

Marseille Saint-Joseph Hospital

Marseille, , France

Site Status

Marseille University Hospital La Conception

Marseille, , France

Site Status

Marseille University Hospital Nord

Marseille, , France

Site Status

Marseille University Hospital

Marseille, , France

Site Status

Meaux Hospital

Meaux, , France

Site Status

Montreuil Hospital CHI André Grégroie

Montreuil, , France

Site Status

Nantes University Hospital

Nantes, , France

Site Status

Nantes Private Hospital Clinique Jules Verne

Nantes, , France

Site Status

Nantes University Hospital

Nantes, , France

Site Status

Paris Hospital Saint-Joseph

Paris, , France

Site Status

Paris Necker University Hospital

Paris, , France

Site Status

Paris University Hospital Armand-Trousseau

Paris, , France

Site Status

Paris University Hospital Bichat

Paris, , France

Site Status

Paris University Hospital Bicêtre

Paris, , France

Site Status

Paris University Hospital Béclère

Paris, , France

Site Status

Paris University Hospital Jean Verdier

Paris, , France

Site Status

Paris University Hospital La Pitié Salpétrière

Paris, , France

Site Status

Paris University Hospital Louis Mourier

Paris, , France

Site Status

Paris University Hospital Necker

Paris, , France

Site Status

Poissy Hospital CHI Poissy-Saint-Germain

Poissy, , France

Site Status

Pontoise Hospital René Dubos

Pontoise, , France

Site Status

Rennes Private Hospital Clinique Mutualiste La Sagesse

Rennes, , France

Site Status

Rennes University Hospital

Rennes, , France

Site Status

Saint-Grégoire Private Hospital

Rennes, , France

Site Status

Roubaix Hospital

Roubaix, , France

Site Status

Saint-Herblain Private Hospital Polyclinique de l'Atlantique

Saint-Herblain, , France

Site Status

Saint-Mande Army Hospital Begin

Saint-Mandé, , France

Site Status

Saint-Martin-d'Hère Private Hospital Clinique Belledonne

Saint-Martin-d'Hères, , France

Site Status

Strasbourg Private Hospital Clinique Adassa

Strasbourg, , France

Site Status

Strasbourg University Hospital

Strasbourg, , France

Site Status

Toulouse Private Hospital Clinique Sarrus Teinturiers

Toulouse, , France

Site Status

Toulouse University Hospital P. DE VIGUIER

Toulouse, , France

Site Status

Toulouse University Hospital

Toulouse, , France

Site Status

Countries

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France

References

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Thomas C, Durand-Zaleski I, Frenkiel J, Mirallie S, Leger A, Cheillan D, Picard C, Mahlaoui N, Riche VP, Roussey M, Sebille V, Rabetrano H, Dert C, Fischer A, Audrain M. Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results. Clin Immunol. 2019 May;202:33-39. doi: 10.1016/j.clim.2019.03.012. Epub 2019 Apr 1.

Reference Type DERIVED
PMID: 30946917 (View on PubMed)

Audrain MAP, Leger AJC, Hemont CAF, Mirallie SM, Cheillan D, Rimbert MGM, Le Thuaut AM, Sebille-Rivain VA, Prat A, Pinel EMQ, Divry E, Dert CGL, Fournier MAG, Thomas CJC. Newborn Screening for Severe Combined Immunodeficiency: Analytic and Clinical Performance of the T Cell Receptor Excision Circle Assay in France (DEPISTREC Study). J Clin Immunol. 2018 Oct;38(7):778-786. doi: 10.1007/s10875-018-0550-7. Epub 2018 Sep 24.

Reference Type DERIVED
PMID: 30251145 (View on PubMed)

Other Identifiers

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RC14_0030

Identifier Type: -

Identifier Source: org_study_id

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