Severe Combined ImmunodeficiencyNCT02590328
Neonatal Screening of Severe Combined Immunodeficiencies
An observational study of Severe Combined Immunodeficiency and Neonatal Screening, run by Children's Hospital of Fudan University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 28 days
- Conditions the study is for
- Severe Combined Immunodeficiency, Neonatal Screening
- How many people
- 180,000 participants
- Where
- 1 siteChina
- Study dates
- Dec 2015to Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 28 days
- All sexes
- No healthy volunteers
- Child
Study population: Screening newborns will be selected from all cooperative hospitals of Neonatal Screening Programme in Shanghai who was born from 2016 to 2020.
Who may be able to join
- No more than 28 days old
- Newborns who was born in Shanghai and in 2016 to 2020
- Blood sample card was collected in 72 hours after birth
Who cannot join
- Lack of parental consent
- Sample card was damaged
Trial locations and contacts
1 site in 1 country.
China1 site
Children's Hospital of Fudan University
Shanghai, Shanghai Municipality
About this study
Official title: Generalized Neonatal Screening for Severe Combined Immunodeficiencies (SCID) by Quantification of TRECs
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.
Read the 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.
- Keywords
- Neonatal Screening, Severe Combined Immunodeficiency, Immunologic Deficiency Syndromes, DNA Repair-Deficiency Disorders, T-cell Receptor Excision Circle
- Medical subject headings
- Severe Combined Immunodeficiency, Immunologic Deficiency Syndromes, DNA Repair-Deficiency Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
prevalence of SCID
Measured: At 28 days after birth
Secondary outcomes (1)
Number of detected SCID patients
Measured: At 28 days after birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2015 (estimated)
- Study startDec 2015
- Primary completionDec 2020
- Study completionDec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Severe Combined ImmunodeficiencyStudies of the same condition, open and under way.
- More trials run by Children's Hospital of Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 180,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jinqiao Sun, Children's Hospital of Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02590328
- Sponsor's protocol ID
- NSSCID
- Status last verified
- Jan 2021
- First submitted
- 27 Oct 2015
- Last updated
- 5 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Kobrynski L. Newborn screening for severe combined immune deficiency (technical and political aspects). Curr Opin Allergy Clin Immunol. 2015 Dec;15(6):539-46. doi: 10.1097/ACI.0000000000000221.
PubMed 26485096de Pagter AP, Bredius RG, Kuijpers TW, Tramper J, van der Burg M, van Montfrans J, Driessen GJ; Dutch Working Party for Immunodeficiencies. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening. Eur J Pediatr. 2015 Sep;174(9):1183-8. doi: 10.1007/s00431-015-2518-4. Epub 2015 Apr 1.
PubMed 25875249Rozmus J, Junker A, Thibodeau ML, Grenier D, Turvey SE, Yacoub W, Embree J, Haddad E, Langley JM, Ramsingh RM, Singh VA, Long R, Schultz KR. Severe combined immunodeficiency (SCID) in Canadian children: a national surveillance study. J Clin Immunol. 2013 Nov;33(8):1310-6. doi: 10.1007/s10875-013-9952-8.
PubMed 24122030Puck JM, Routes J, Filipovich AH, Sullivan K. Expert commentary: practical issues in newborn screening for severe combined immune deficiency (SCID). J Clin Immunol. 2012 Feb;32(1):36-8. doi: 10.1007/s10875-011-9598-3. Epub 2011 Oct 20. No abstract available.
PubMed 22012274Burroughs L, Woolfrey A. Hematopoietic cell transplantation for treatment of primary immune deficiencies. Cell Ther Transplant. 2010 Aug 31;2(8):10.3205/ctt-2010-en-000077.01. doi: 10.3205/ctt-2010-en-000077.01.
PubMed 21152385Puck JM. Neonatal screening for severe combined immune deficiency. Curr Opin Allergy Clin Immunol. 2007 Dec;7(6):522-7. doi: 10.1097/ACI.0b013e3282f14a2a.
PubMed 17989529Puck JM; SCID Newborn Screening Working Group. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol. 2007 Oct;120(4):760-8. doi: 10.1016/j.jaci.2007.08.043.
PubMed 17931561de Silva R, Gunasena S, Ratnayake D, Wickremesinghe GD, Kumarasiri CD, Pushpakumara BA, Deshpande J, Kahn AL, Sutter RW. Prevalence of prolonged and chronic poliovirus excretion among persons with primary immune deficiency disorders in Sri Lanka. Vaccine. 2012 Dec 14;30(52):7561-5. doi: 10.1016/j.vaccine.2012.10.035. Epub 2012 Oct 22.
PubMed 23099333
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Generalized Neonatal Screening for Severe Combined Immunodeficiencies (SCID) by Quantification of TRECs
- ClinicalTrials.gov ID
- NCT02590328
- Acronym / sponsor ID
- NSSCID
- Keywords
- Neonatal Screening, Severe Combined Immunodeficiency, Immunologic Deficiency Syndromes, DNA Repair-Deficiency Disorders, T-cell Receptor Excision Circle
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 180,000 participants (actual)
- Lead sponsor
- Children's Hospital of Fudan UniversityUniversity, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2021 (actual)
- First posted
- 29 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- Up to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Screening newborns will be selected from all cooperative hospitals of Neonatal Screening Programme in Shanghai who was born from 2016 to 2020.
Key inclusion criteria (3 listed)
- No more than 28 days old
- Newborns who was born in Shanghai and in 2016 to 2020
- Blood sample card was collected in 72 hours after birth
Key exclusion criteria (2 listed)
- Lack of parental consent
- Sample card was damaged
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
prevalence of SCID
Time frame: At 28 days after birth
1 secondary outcome
Number of detected SCID patients
Time frame: At 28 days after birth
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2022.
- Background: PubMed 26485096Kobrynski L. Newborn screening for severe combined immune deficiency (technical and political aspects). Curr Opin Allergy Clin Immunol. 2015 Dec;15(6):539-46. doi: 10.1097/ACI.0000000000000221.
- Background: PubMed 25875249de Pagter AP, Bredius RG, Kuijpers TW, Tramper J, van der Burg M, van Montfrans J, Driessen GJ; Dutch Working Party for Immunodeficiencies. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening. Eur J Pediatr. 2015 Sep;174(9):1183-8. doi: 10.1007/s00431-015-2518-4. Epub 2015 Apr 1.
- Background: PubMed 24122030Rozmus J, Junker A, Thibodeau ML, Grenier D, Turvey SE, Yacoub W, Embree J, Haddad E, Langley JM, Ramsingh RM, Singh VA, Long R, Schultz KR. Severe combined immunodeficiency (SCID) in Canadian children: a national surveillance study. J Clin Immunol. 2013 Nov;33(8):1310-6. doi: 10.1007/s10875-013-9952-8.
- Background: PubMed 22012274Puck JM, Routes J, Filipovich AH, Sullivan K. Expert commentary: practical issues in newborn screening for severe combined immune deficiency (SCID). J Clin Immunol. 2012 Feb;32(1):36-8. doi: 10.1007/s10875-011-9598-3. Epub 2011 Oct 20. No abstract available.
- Background: PubMed 21152385Burroughs L, Woolfrey A. Hematopoietic cell transplantation for treatment of primary immune deficiencies. Cell Ther Transplant. 2010 Aug 31;2(8):10.3205/ctt-2010-en-000077.01. doi: 10.3205/ctt-2010-en-000077.01.
- Background: PubMed 17989529Puck JM. Neonatal screening for severe combined immune deficiency. Curr Opin Allergy Clin Immunol. 2007 Dec;7(6):522-7. doi: 10.1097/ACI.0b013e3282f14a2a.
- Background: PubMed 17931561Puck JM; SCID Newborn Screening Working Group. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol. 2007 Oct;120(4):760-8. doi: 10.1016/j.jaci.2007.08.043.
- Background: PubMed 23099333de Silva R, Gunasena S, Ratnayake D, Wickremesinghe GD, Kumarasiri CD, Pushpakumara BA, Deshpande J, Kahn AL, Sutter RW. Prevalence of prolonged and chronic poliovirus excretion among persons with primary immune deficiency disorders in Sri Lanka. Vaccine. 2012 Dec 14;30(52):7561-5. doi: 10.1016/j.vaccine.2012.10.035. Epub 2012 Oct 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Combined Immunodeficiency and Neonatal Screening, run by Children's Hospital of Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
prevalence of SCID (time frame: At 28 days after birth). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02590328, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2022.