Type1diabetesBABYSCREENNCT04958356
Newborn Screening for Genetic Susceptibility to Type 1 Diabetes and Celiac Disease and Prospective Follow-up Study
An observational study of Type1diabetes and Celiac Disease, run by University of Helsinki at 1 site in Finland.
Trial summary
This is an observational study, in which newborn infants from the general population are screened at birth for HLA-conferred susceptibility to type 1 diabetes and celiac disease. Read more about this study
- Who is it for?
- Ages 1 minute to 10 yearsHealthy volunteers can take part
- Conditions the study is for
- Type1diabetes, Celiac Disease
- How many people
- 9,690 participants
- Where
- 1 siteFinland
- Study dates
- 19 Nov 2018to 31 Dec 2032
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 1 minute to 10 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Delivery hospitals in the Helsinki region. The number of annual births is approximately 13,000. Close to half of the newborn infants will be girls. The investigators expect that around 80% of the families (10,400) will give their informed consent to the genetic screening of their infant. About 9.5% of the infants screened (n=988) will carry HLA-conferred susceptibility to type 1 diabetes and approximately 14% (n=1456) predisposition to celiac disease. The families with at-risk infants will be invited to the autoantibody follow-up to the age of 3 years.
Who may be able to join
- mother has given an informed consent
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
About this study
This is an observational study, in which newborn infants from the general population are screened at birth for HLA-conferred susceptibility to type 1 diabetes and celiac disease. The participants carrying genetic susceptibility to type 1 diabetes (approximately 9.5%) will be analyzed for diabetes-associated autoantibodies at the age of 1, 2 and 3 years, while those predisposed to celiac disease (about 14%) will be screened for tissue transglutaminase antibodies at the age of 1 and 3 years. The intention is to screen annually 10,400 newborn infants for a period of 3 years. About 988 infants are each year identified as a child at risk for type 1 diabetes, and it is expected that around 80% of the families with such a child are willing to join the autoantibody screening. Approximately 1456 infants are each year recognized as a child at risk for celiac disease, and again the expectation is that 80% of the families will join the antibody screening program.
Read the detailed description
The aim of the BABYSCREEN project is to identify newborn infants with HLA-conferred susceptibility to T1D and/or CeD from the general population and to observe such children for the appearance of disease-associated autoantibodies and clinical disease up to the age of 1-3 years. The plan is to screen all infants with maternal consent born in one of the two delivery hospitals in the metropolitan Helsinki area, i.e. Women's Hospital in Helsinki and Jorvi Hospital in Espoo. The parents to be will be informed about the study and invited during pregnancy to take part in the study after the birth of their baby. The pregnant woman is asked to give her electronic consent to participation through the Women's website (https://www.terveyskyla.fi/naistalo) or a written informed consent on paper after both parents have acquainted themselves with the study. The only inclusion criterion will be informed consent signed by the mother.
The screening activity will be carried out over a 3-year period. The annual number of births in the Helsinki region is about 13,000. It is expected that at least 80% of the parents will give their informed consent to participation in the study. Accordingly about 31,200 newborn infants would be screened for genetic susceptibility to T1D and CeD. The following HLA genotypes represent those predisposing to T1D: (i) the high-risk genotype (DR3)-DQA1*05-DQB1*02/DRB1*04:01/2/4/5;)-DQA1*03-DQB1*03:02; (ii) the moderately increased-risk genotype DRB1*04:01/2/5-DQA1*03-DQB1*03:02/neutral haplotype; (iii) the slightly increased-risk genotype (DR3)-DQA1*05-DQB1*02/ (DR9)-DQA1*03-DQB1*03:03; (iv) DR4 homozygosity DRB1*04:01/2/4/5)-DQA1*03-DQB1*03:02/DRB1*04:01/2/4/5)-DQA1*03-DQB1*03: 02; and (v) DR3 homozygosity (DR3)-DQA1*05-DQB1*02/(DR3)-DQA1*05-DQB1*02. To cover those with genetic susceptibility to CeD also all other genotypes including the DR3-DQ2 haplotype will be identified. Their proportion among Finnish infants is 14%. This screening protocol identifying 23.5% of the screened infants as at-risk children has a sensitivity of 64.6% for T1D and more than 90% for CeD. Around 9.5% will carry HLA susceptibility to T1D and an additional 14% predisposition to CeD. With an expected consent rate of 80%, approximately 988 participants with HLA-defined predisposition to T1D (about 370 of them having also susceptibility to CeD) and 1,456 participants with HLA-conferred susceptibility to only CeD would be ended up each year. In addition, DNA will later be extracted from cord blood to identify genes outside the HLA gene region conferring increased risk for T1D and/or CeD.
Families with a baby carrying a predisposing HLA genotype are invited to follow-up for the appearance of predictive autoantibodies. The participants genetically at risk for T1D will be screened with the guardians' consents annually for four diabetes predictive autoantibodies and followed up to 1-3 years of age. If a participant tests positive for one or more autoantibodies at a given age, he/she will be invited for a second sample within 2 months from the first positive sample. If a child test positive for multiple (≥ 2) autoantibodies, HbA1c will be analyzed and an oral glucose tolerance test carried out to diagnose or exclude dysglycemia. Dysglycemic participants will be referred to a pediatric unit taking care of children with T1D for continued monitoring.
The participants at risk for CeD are screened for tissue transglutaminase antibodies (tTGA) at the age of 1 and 3 years. If a child tests positive for such autoantibodies, endomysial antibodies will be analyzed. Children testing positive for both autoantibodies will be referred to a pediatríc gastroenterologist for consultation.
One objective of this project is to prevent diabetic ketoacidosis in those participants who progress to clinical T1D and to diagnose early the development of CeD to prevent its complications. This serves also as a demonstration project for the potential benefits achieved with early population-based screening of two common chronic childhood disorders.
The following information will be collected from the participants in the screening study; gestational age, route of delivery, gender, birth weight and length, head circumference, and Apgar score. In addition, information on autoimmune diseases in family will be collected at the beginning of the study and at the last study visit by electronic questionnaire, since any autoimmune disease in the family increases the risk of T1D and/or CeD in other family members. Growth will be monitored in the participants in the follow-up study.
Those at risk for T1D will be screened annually for the four biochemical autoantibodies predicting T1D, i.e. insulin autoantibodies (IAA) and antibodies to glutamate decarboxylase GADA), islet antigen 2 (IA-2A) and zinc transporter 8 (ZnT8A). These autoantibodies are analyzed with specific radiobinding assays. If a participant tests positive for one or more autoantibodies at a given age, he/she will be invited for a second sample within 2 months from the first positive sample. Participants with confirmed positivity for multiple (≥2) autoantibodies, will be invited for a new visit for assessing possible signs of dysglycemia. A HbA1c sample is taken and a 2-hour oral glucose tolerance test will be carried out. If the child has signs of dysglycemia, he/she will be referred to a pediatric unit taking care of patients with T1D for contínued follow-up. Participants with confirmed positivity for T1D associated autoantibodies at the last follow-up sample, will be invited to come to a new visit for assessing T1D associated autoantibodies after 3 years.
The children predisposed to CeD will be analyzed for IgA and IgG class tTGA at the age of 1 or 1 and 3 years of age. If the child tests unequivocally positive for tTGA, the positive sample will be analyzed for endomysial antibodies. If the participant has both autoantibodies, she/he will be referred to a pediatric gastroenterologists for consideration of duodenal biopsy. Participants with confirmed positivity for tTGA at the last follow-up sample, will be invited to come to a new visit for assessing CeD associated autoantibodies after 3 years.
- Conditions
- Type1diabetes, Celiac Disease
- Keywords
- type 1 diabetes, celiac disease
- Medical subject headings
- Celiac Disease, Diabetes Mellitus, Type 1
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 |
|---|---|---|
| Children with increased risk for T1D and/or CeD | The participants carrying HLA-conferred susceptibility to type 1 diabetes will be screened annually for four diabetes predictive autoantibodies and followed up to 1-3 years of age. The participants carrying HLA-conferred susceptibility to celiac disease are screened for tissue transglutaminase antibodies (tTGA) at the age of 1 and 3 years. If a child tests positive for such autoantibodies, endomysial antibodies will be analyzed. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with confirmed positivity for at least one diabetes-associated autoantibody (insulin autoantibodies and antibodies to GAD65, islet antigen 2 and zinc transporter 8) or confirmed positivity for tissue transglutaminase antibodies
Antibodies listed in the title are analyzed by specific radiobinding assays. The cut-off limit of antibody positivity is defined based on 350 healthy children. Confirmed positivity refers to positive test results in at least two sequential samples. The autoantibodies are analyzed at the age of 1, 2 and 3 years. If a child tests positive, the result will be confirmed in a second sample taken within 2 months after the initially positive sample. The autoantibody screening allows the identification of participants who will present with preclinical or clinical disease before the age of 3 years. This will minimize the frequency of diabetic ketoacidosis among those participants, who progress to clinical T1D. Untreated CeD is associated with health sequelae. Early diagnosis of celiac disease based on screening for genetic disease susceptibility at birth combined with follow-up for the appearance of disease predictive autoantibodies will effectively prevent such problems.
Measured: December 31, 2022
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2021
- Study start19 Nov 2018
- Primary completion31 Dec 2031 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type1diabetesStudies of the same condition, open and under way.
- 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 9,690 participants (actual)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- University of Helsinki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mikael Knip, University of Helsinki
- Investigators
- Mikael Knip, MD, Principal investigator, University of Helsinki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04958356
- Sponsor's protocol ID
- 728/2018
- Acronym
- BABYSCREEN
- Status last verified
- Jul 2021
- First submitted
- 27 Feb 2019
- Last updated
- 12 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Newborn Screening for Genetic Susceptibility to Type 1 Diabetes and Celiac Disease and Prospective Follow-up Study
- ClinicalTrials.gov ID
- NCT04958356
- Acronym / sponsor ID
- BABYSCREEN / 728/2018
- Conditions
- Type1diabetes, Celiac Disease
- Keywords
- type 1 diabetes, celiac disease
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 9,690 participants (actual)
- Lead sponsor
- University of HelsinkiUniversity, hospital or other
- Study start
- 19 Nov 2018 (actual)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 12 Jul 2021 (actual)
- 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.
This is an observational study, in which newborn infants from the general population are screened at birth for HLA-conferred susceptibility to type 1 diabetes and celiac disease. The participants carrying genetic susceptibility to type 1 diabetes (approximately 9.5%) will be analyzed for diabetes-associated autoantibodies at the age of 1, 2 and 3 years, while those predisposed to celiac disease (about 14%) will be screened for tissue transglutaminase antibodies at the age of 1 and 3 years. The intention is to screen annually 10,400 newborn infants for a period of 3 years. About 988 infants are each year identified as a child at risk for type 1 diabetes, and it is expected that around 80% of the families with such a child are willing to join the autoantibody screening. Approximately 1456 infants are each year recognized as a child at risk for celiac disease, and again the expectation is that 80% of the families will join the antibody screening program.
Detailed description
The aim of the BABYSCREEN project is to identify newborn infants with HLA-conferred susceptibility to T1D and/or CeD from the general population and to observe such children for the appearance of disease-associated autoantibodies and clinical disease up to the age of 1-3 years. The plan is to screen all infants with maternal consent born in one of the two delivery hospitals in the metropolitan Helsinki area, i.e. Women's Hospital in Helsinki and Jorvi Hospital in Espoo. The parents to be will be informed about the study and invited during pregnancy to take part in the study after the birth of their baby. The pregnant woman is asked to give her electronic consent to participation through the Women's website (https://www.terveyskyla.fi/naistalo) or a written informed consent on paper after both parents have acquainted themselves with the study. The only inclusion criterion will be informed consent signed by the mother.
The screening activity will be carried out over a 3-year period. The annual number of births in the Helsinki region is about 13,000. It is expected that at least 80% of the parents will give their informed consent to participation in the study. Accordingly about 31,200 newborn infants would be screened for genetic susceptibility to T1D and CeD. The following HLA genotypes represent those predisposing to T1D: (i) the high-risk genotype (DR3)-DQA1*05-DQB1*02/DRB1*04:01/2/4/5;)-DQA1*03-DQB1*03:02; (ii) the moderately increased-risk genotype DRB1*04:01/2/5-DQA1*03-DQB1*03:02/neutral haplotype; (iii) the slightly increased-risk genotype (DR3)-DQA1*05-DQB1*02/ (DR9)-DQA1*03-DQB1*03:03; (iv) DR4 homozygosity DRB1*04:01/2/4/5)-DQA1*03-DQB1*03:02/DRB1*04:01/2/4/5)-DQA1*03-DQB1*03: 02; and (v) DR3 homozygosity (DR3)-DQA1*05-DQB1*02/(DR3)-DQA1*05-DQB1*02. To cover those with genetic susceptibility to CeD also all other genotypes including the DR3-DQ2 haplotype will be identified. Their proportion among Finnish infants is 14%. This screening protocol identifying 23.5% of the screened infants as at-risk children has a sensitivity of 64.6% for T1D and more than 90% for CeD. Around 9.5% will carry HLA susceptibility to T1D and an additional 14% predisposition to CeD. With an expected consent rate of 80%, approximately 988 participants with HLA-defined predisposition to T1D (about 370 of them having also susceptibility to CeD) and 1,456 participants with HLA-conferred susceptibility to only CeD would be ended up each year. In addition, DNA will later be extracted from cord blood to identify genes outside the HLA gene region conferring increased risk for T1D and/or CeD.
Families with a baby carrying a predisposing HLA genotype are invited to follow-up for the appearance of predictive autoantibodies. The participants genetically at risk for T1D will be screened with the guardians' consents annually for four diabetes predictive autoantibodies and followed up to 1-3 years of age. If a participant tests positive for one or more autoantibodies at a given age, he/she will be invited for a second sample within 2 months from the first positive sample. If a child test positive for multiple (≥ 2) autoantibodies, HbA1c will be analyzed and an oral glucose tolerance test carried out to diagnose or exclude dysglycemia. Dysglycemic participants will be referred to a pediatric unit taking care of children with T1D for continued monitoring.
The participants at risk for CeD are screened for tissue transglutaminase antibodies (tTGA) at the age of 1 and 3 years. If a child tests positive for such autoantibodies, endomysial antibodies will be analyzed. Children testing positive for both autoantibodies will be referred to a pediatríc gastroenterologist for consultation.
One objective of this project is to prevent diabetic ketoacidosis in those participants who progress to clinical T1D and to diagnose early the development of CeD to prevent its complications. This serves also as a demonstration project for the potential benefits achieved with early population-based screening of two common chronic childhood disorders.
The following information will be collected from the participants in the screening study; gestational age, route of delivery, gender, birth weight and length, head circumference, and Apgar score. In addition, information on autoimmune diseases in family will be collected at the beginning of the study and at the last study visit by electronic questionnaire, since any autoimmune disease in the family increases the risk of T1D and/or CeD in other family members. Growth will be monitored in the participants in the follow-up study.
Those at risk for T1D will be screened annually for the four biochemical autoantibodies predicting T1D, i.e. insulin autoantibodies (IAA) and antibodies to glutamate decarboxylase GADA), islet antigen 2 (IA-2A) and zinc transporter 8 (ZnT8A). These autoantibodies are analyzed with specific radiobinding assays. If a participant tests positive for one or more autoantibodies at a given age, he/she will be invited for a second sample within 2 months from the first positive sample. Participants with confirmed positivity for multiple (≥2) autoantibodies, will be invited for a new visit for assessing possible signs of dysglycemia. A HbA1c sample is taken and a 2-hour oral glucose tolerance test will be carried out. If the child has signs of dysglycemia, he/she will be referred to a pediatric unit taking care of patients with T1D for contínued follow-up. Participants with confirmed positivity for T1D associated autoantibodies at the last follow-up sample, will be invited to come to a new visit for assessing T1D associated autoantibodies after 3 years.
The children predisposed to CeD will be analyzed for IgA and IgG class tTGA at the age of 1 or 1 and 3 years of age. If the child tests unequivocally positive for tTGA, the positive sample will be analyzed for endomysial antibodies. If the participant has both autoantibodies, she/he will be referred to a pediatric gastroenterologists for consideration of duodenal biopsy. Participants with confirmed positivity for tTGA at the last follow-up sample, will be invited to come to a new visit for assessing CeD associated autoantibodies after 3 years.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Target follow-up
- 10 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children with increased risk for T1D and/or CeD | – | –The participants carrying HLA-conferred susceptibility to type 1 diabetes will be screened annually for four diabetes predictive autoantibodies and followed up to 1-3 years of age. The participants carrying HLA-conferred susceptibility to celiac disease are screened for tissue transglutaminase antibodies (tTGA) at the age of 1 and 3 years. If a child tests positive for such autoantibodies, endomysial antibodies will be analyzed. |
Who may qualify
- Ages
- 1 minute to 10 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Delivery hospitals in the Helsinki region. The number of annual births is approximately 13,000. Close to half of the newborn infants will be girls. The investigators expect that around 80% of the families (10,400) will give their informed consent to the genetic screening of their infant. About 9.5% of the infants screened (n=988) will carry HLA-conferred susceptibility to type 1 diabetes and approximately 14% (n=1456) predisposition to celiac disease. The families with at-risk infants will be invited to the autoantibody follow-up to the age of 3 years.
Key inclusion criteria (1 listed)
- mother has given an informed consent
Key exclusion criteria (1 listed)
- -
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
Number of participants with confirmed positivity for at least one diabetes-associated autoantibody (insulin autoantibodies and antibodies to GAD65, islet antigen 2 and zinc transporter 8) or confirmed positivity for tissue transglutaminase antibodies
Time frame: December 31, 2022
Antibodies listed in the title are analyzed by specific radiobinding assays. The cut-off limit of antibody positivity is defined based on 350 healthy children. Confirmed positivity refers to positive test results in at least two sequential samples. The autoantibodies are analyzed at the age of 1, 2 and 3 years. If a child tests positive, the result will be confirmed in a second sample taken within 2 months after the initially positive sample. The autoantibody screening allows the identification of participants who will present with preclinical or clinical disease before the age of 3 years. This will minimize the frequency of diabetic ketoacidosis among those participants, who progress to clinical T1D. Untreated CeD is associated with health sequelae. Early diagnosis of celiac disease based on screening for genetic disease susceptibility at birth combined with follow-up for the appearance of disease predictive autoantibodies will effectively prevent such problems.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2021.
- 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.
Mikael Knip, MD principal investigator
University of Helsinki
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 Type1diabetes and Celiac Disease, run by University of Helsinki at 1 site in Finland.
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 1 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 12 Jul 2021. 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 Finland. 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?
This study is still under way. Results are not available in the source record yet.
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?
Number of participants with confirmed positivity for at least one diabetes-associated autoantibody (insulin autoantibodies and antibodies to GAD65, islet antigen 2 and zinc transporter 8) or confirmed positivity for tissue transglutaminase antibodies (time frame: December 31, 2022). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jul 2021.