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Neonatal Screening of Severe Combined Immunodeficiencies

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02590328
Recruitment Status : Recruiting
First Posted : October 29, 2015
Last Update Posted : March 30, 2018
Information provided by (Responsible Party):
Jinqiao Sun, Children's Hospital of Fudan University

Brief Summary:
The goal of the proposed research is to observe the prevalence and establish the validity of a newborn screening method for severe combined immunodeficiency (SCID). The assay to be used is developed on the basis of PCR quantification of T-cell receptor excision circles (TRECs) that is absent in SCID patients, thus correlating with the disease.

Condition or disease
Severe Combined Immunodeficiency Neonatal Screening

Detailed Description:

Severe combined Immunodeficiencies (SCID) are a group of inherited diseases of the immune system by characterized profound abnormalities of B and 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.To show that early diagnosis of SCID with a TREC screening assay can warrant timely treatment of the disease and avoid life-threatening infections on patients. Babies with SCID are unable to fight infections. They become severely ill in their first months of life and do not survive unless their immune systems can be restored. SCID can be treated by bone marrow transplant if recognized early. We undertake the task of newborn screening in the whole region of Shanghai, So the newborn screening test to be employed in this study is designed to diagnose SCID before infections occur. Through this study, we hope to confirm the prevalence of SCID in China and the benefits of newborn screening for early diagnosis of SCID.

Quantification of TRECs (T-cell receptor excision circles) in DNA extracted from Guthrie samples is a sensitive screening test for Specific and SCID. TRECs are small-circle DNA molecules which are by-products of T cell maturation in the thymus, and their numbers reflect the number of recently emigrated T-cells from the thymus. Since all infants with SCID have a profound decrease in T-lymphocytes no matter what gene mutations are involved, logically the number of TRECs present in blood collected via dried blood spots 1-2 days post delivery on SCID babies should be very low when compared with healthy newborns. The TREC assay includes DNA extraction from a 3 mm punch of dried blood specimen in a 96-well plate format. The extracted DNA undergoes Real-time qPCR procedure on 7900 HT Fast Real-time PCR System (ABI). The TREC copy number is calculated relative to a standard curve generated from serially diluted plasmids which contain a known number of TREC. The investigators propose in this study to perform a neonatal screening of SCID, in a population of 200,000 babies over a period of three years. The investigators propose to study the incidence of SCID, mortality & rate of disability, clinical utility and SCID screening to demonstrate that could result in a broad benefit to individuals detected, making screening relatively efforts in spite of the low incidence of the disease.

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Study Type : Observational
Estimated Enrollment : 200000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Generalized Neonatal Screening for Severe Combined Immunodeficiencies (SCID) by Quantification of TRECs
Actual Study Start Date : December 2015
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Screened patients
SCID screening: some drops of blood are placed on a second Guthrie card when current screening 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.

Primary Outcome Measures :
  1. prevalence of SCID [ Time Frame: At 28 days after birth ]

Secondary Outcome Measures :
  1. Number of detected SCID patients [ Time Frame: At 28 days after birth ]

Biospecimen Retention:   Samples With DNA
Some drops of blood stored on the neonatal screening card (Guthrie card) as a source of DNA to screening. Samples 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 28 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Screening newborns will be selected from all cooperative hospitals of Neonatal Screening Programme in Shanghai who was born from 2016 to 2020.

Inclusion Criteria:

  1. No more than 28 days old
  2. Newborns who was born in Shanghai and in 2016 to 2020
  3. Blood sample card was collected in 72 hours after birth

Exclusion Criteria:

  1. Lack of parental consent
  2. Sample card was damaged

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): NCT02590328

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Contact: Jinqiao Sun, Ph.D.,M.D
Contact: Xiaochuan Wang, Ph.D.,M.D

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China, Shanghai
Children's Hospital of Fudan University Recruiting
Shanghai, Shanghai, China
Sponsors and Collaborators
Children's Hospital of Fudan University


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Responsible Party: Jinqiao Sun, Professor, Children's Hospital of Fudan University Identifier: NCT02590328     History of Changes
Other Study ID Numbers: NSSCID
First Posted: October 29, 2015    Key Record Dates
Last Update Posted: March 30, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Jinqiao Sun, Children's Hospital of Fudan University:
Neonatal Screening
Severe Combined Immunodeficiency
Immunologic Deficiency Syndromes
DNA Repair-Deficiency Disorders
T-cell Receptor Excision Circle

Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Severe Combined Immunodeficiency
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases