Diabetes Mellitus, Type 1
Conditions
Keywords
Type 1 diabetes, T1D, Diabetes mellitus, Autoantigen, Prevention, at risk for developing type 1 diabetes, Juvenile diabetes, Autoimmune diabetes, Corona, COVID-19, Viral infection, Viral infection surveillance, Immune response, Metabolism
Brief summary
The study GPPAD-05 AVAnT1A is a phase 4 clinical trial intending to enroll 2252 children, who will be randomly assigned to receive COVID-19 vaccination (Comirnaty® 3 μg Omicron XBB.1.5 or new variant Comirnaty vaccines ) or placebo from age 6 months. The study is an investigator initiated, randomized, controlled, multicentre, multinational, primary prevention trial for children at increased risk of type 1 diabetes. The primary objective is to determine whether vaccination of children with elevated genetic risk for type 1 diabetes against COVID-19 from 6 months of age reduces the cumulative incidence of islet autoantibodies or type 1 diabetes in childhood. Secondary objectives are: 1. to determine whether vaccination against COVID-19 similarly reduces the cumulative incidence of multiple islet autoantibodies in childhood. 2. to determine whether vaccination against COVID-19 similarly reduces the cumulative incidence of type 1 diabetes in childhood and 3. to determine whether vaccination against COVID-19 similarly reduces the cumulative incidence of celiac disease-associated transglutaminase autoantibodies in childhood. Further exploratory objectives are described in the study protocol. Study participants will be identified through an ongoing study screening for genetic risk of type 1 diabetes using a polygenic risk score (NCT03316261). Eligible participants will be enrolled at age 3.00 to 4.00 months (baseline visit). Randomization to vaccine or placebo will occur at age 6.00 to 7.00 months at visit 2. Consent will be obtained by the custodial parents prior to enrollment.
Interventions
DRUGComirnaty Injectable Product
Vaccination
Vaccination
Sponsors
Helmholtz Zentrum München
University Hospital Carl Gustav Carus
Kinderkrankenhaus auf der Bult
Skane University Hospital
Universitaire Ziekenhuizen KU Leuven
Newcastle-upon-Tyne Hospitals NHS Trust
Cambridge University Hospitals NHS Foundation Trust
Birmingham Women's and Children's NHS Foundation Trust
Technical University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Months to 4 Months
Healthy volunteers
Yes
Inclusion criteria
1. Ages between 3.00 and 4.00 months at the time of enrollment. 2. A high genetic risk (\>10%) to develop islet autoantibodies by age 6 years as determined by a HLA DR/DQ genotype, polygenic risk score and first-degree family history of type 1 diabetes status. 3. Written informed consent signed by the custodial parent(s).
Exclusion criteria
1. Previous hypersensitivity to the excipients of the vaccine. 2. Any medical condition, concomitant disease or treatment that may interfere with the assessments or may jeopardize the participant's safe participation in the study. These include immune deficiencies, and conditions or treatments that lead to immune suppression. 3. Likely poor compliance due to expected change in residency. 4. Diagnosis of diabetes prior to recruitment or randomisation 5. Current use of any other investigational drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Persistent confirmed islet autoantibodies or type 1 diabetes | Through study completion, up to 6 years | The primary outcome is the elapsed time from first vaccination to the development of persistent confirmed islet autoantibodies or type 1 diabetes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Persistent confirmed multiple islet autoantibodies | Through study completion, up to 6 years | Elapsed time from first vaccination to persistent confirmed multiple islet autoantibodies; |
| Type 1 diabetes | Through study completion, up to 6 years | Elapsed time from first vaccination to type 1 diabetes. |
| Persistent confirmed transglutaminase autoantibodies | Through study completion, up to 6 years | Elapsed time from first vaccination to the development of persistent confirmed transglutaminase autoantibodies. |
Countries
Austria, Belgium, Germany, Sweden, United Kingdom
Contacts
Primary ContactAnette-G. Ziegler, Prof. Dr.
Backup ContactPeter Achenbach, Prof. Dr.
Outcome results
None listed