Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04958356 |
| Other study ID # |
728/2018 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 19, 2018 |
| Est. completion date |
December 31, 2032 |
Study information
| Verified date |
July 2021 |
| Source |
University of Helsinki |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical 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. 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.
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.
