Anti-viral action against type 1 diabetes autoimmunity: The GPPAD-AVAnT1A study protocol

Sandra Hummel^{1

2}, Alexandra Käßl¹, Stefanie Arnolds¹, Peter Achenbach^{1

2}, Reinhard Berner³, Kristina Casteels^{4

5}, Heikki Hyöty⁶, Olga Kordonouri⁷, Helena Elding Larsson^{8

9}, Markus Lundgren^{9

10}, M Loredana Marcovecchio¹¹, Catherine Owen¹², Markus Pfirrmann¹³, Steve Robson¹², Agnieszka Szadkowska¹⁴, Agnieszka Szypowska¹⁵, Timothy Tree¹⁶, Andreas Weiss¹, Anette-Gabriele Ziegler^{1

2}, Ezio Bonifacio^{17

18}; GPPAD Study Group

Affiliations

¹ Institute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany.
² Technical University Munich, School of Medicine and Health, Forschergruppe Diabetes at Klinikum rechts der Isar, Munich, Germany.
³ Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁴ Department of Pedriatrics, University Hospitals Leuven, Leuven, Belgium.
⁵ Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
⁶ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁷ Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.
⁸ Department of Paediatrics, Skane University Hospital, Malmö, Sweden.
⁹ Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
¹⁰ Department of Pediatrics, Kristianstad Hospital, Kristianstad, Sweden.
¹¹ University of Cambridge, Department of Paediatrics, and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹² General Paediatrics, The Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
¹³ Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität München, Munich, Germany.
¹⁴ Department of Paediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland.
¹⁵ Department of Paediatric Diabetology and Paediatrics, Medical University of Warsaw, Warsaw, Poland.
¹⁶ Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, UK.
¹⁷ Center for Regenerative Therapies Dresden (CRTD), Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
¹⁸ Paul Langerhans Institute Dresden of the Helmholtz Munich at University Hospital Carl Gustav Carus and Faculty of Medicine, TU Dresden, Germany.

PMID: 39916680
PMCID: PMC11799962
DOI: 10.1016/j.conctc.2025.101434

Anti-viral action against type 1 diabetes autoimmunity: The GPPAD-AVAnT1A study protocol

Sandra Hummel et al. Contemp Clin Trials Commun. 2025.

. 2025 Jan 20:44:101434.

doi: 10.1016/j.conctc.2025.101434. eCollection 2025 Apr.

Authors

Affiliations

¹ Institute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany.
² Technical University Munich, School of Medicine and Health, Forschergruppe Diabetes at Klinikum rechts der Isar, Munich, Germany.
³ Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁴ Department of Pedriatrics, University Hospitals Leuven, Leuven, Belgium.
⁵ Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
⁶ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁷ Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.
⁸ Department of Paediatrics, Skane University Hospital, Malmö, Sweden.
⁹ Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
¹⁰ Department of Pediatrics, Kristianstad Hospital, Kristianstad, Sweden.
¹¹ University of Cambridge, Department of Paediatrics, and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹² General Paediatrics, The Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
¹³ Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität München, Munich, Germany.
¹⁴ Department of Paediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland.
¹⁵ Department of Paediatric Diabetology and Paediatrics, Medical University of Warsaw, Warsaw, Poland.
¹⁶ Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, UK.
¹⁷ Center for Regenerative Therapies Dresden (CRTD), Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
¹⁸ Paul Langerhans Institute Dresden of the Helmholtz Munich at University Hospital Carl Gustav Carus and Faculty of Medicine, TU Dresden, Germany.

PMID: 39916680
PMCID: PMC11799962
DOI: 10.1016/j.conctc.2025.101434

Abstract

Viral infections in the first year of life are associated with islet autoimmunity and type 1 diabetes risk. The Anti-Viral Action against Type 1 Diabetes Autoimmunity (AVAnT1A)- study is a clinical phase IV investigator initiated, randomised, controlled, multicentre, primary prevention trial conducted to determine whether vaccination against COVID-19 from 6 months of age reduces the cumulative incidence of islet autoantibodies or type 1 diabetes in children with elevated genetic risk. Additionally, it investigates the role of viral infections in the etiology of islet autoimmunity by intense surveillance within the first two years of life. Infants aged 3.00-4.00 months from Germany, Belgium, UK and Sweden are eligible if they have a >10 % expected risk to develop islet autoantibodies by age 6 years as determined by HLA DR/DQ genotype, polygenic risk score and family history of type 1 diabetes. A total of 2252 eligible children are randomized 1:1 to COVID-19 vaccine (Comirnaty® 3 μg Omicron XBB.1.5 or future new variants) or placebo (0.9 % Sodium Chloride) administered three times. Children are followed until the minimum age of 2.5 years and maximum age of 6 years. The intervention is accompanied by analyses of immune and metabolic parameters to determine changes induced by viral infections and to investigate mechanisms by which viral infection may lead to islet autoimmunity. The Sponsor is the Klinikum rechts der Isar, Technical University Munich. The study was approved by Clinical Trials Information System (CTIS, EU Trial number: 2023-507348-35-00) and by Integrated Research Application System (IRAS, IRAS-ID: 1009668).

Keywords: COVID-19; Infection; Islet autoimmunity; Type 1 diabetes; vaccination.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ezio Bonifacio reports financial support was provided by Leona M. and Harry B. Helmsley Charitable Trust. Reinhard Berner reports financial support was provided by Leona M. and Harry B. Helmsley Charitable Trust. Anette-Gabriele Ziegler reports a relationship with Sanofi that includes: board membership. Anette-Gabriele Ziegler reports a relationship with Provention Bio Inc that includes: board membership. Anette-Gabriele Ziegler reports a relationship with ITB-Med that includes: board membership. Anette-Gabriele Ziegler reports a relationship with Sanofi Aventis France that includes: board membership. M. Loredana Marcovecchio reports a relationship with Sanofi that includes: consulting or advisory. Anette-Gabriele Ziegler reports a relationship with Sanofi Germany that includes: speaking and lecture fees. Ezio Bonifacio reports a relationship with Sanofi that includes: speaking and lecture fees. Ezio Bonifacio reports a relationship with Sanofi that includes: travel reimbursement. Sandra Hummel reports a relationship with Sanofi that includes: travel reimbursement. Sandra Hummel reports a relationship with Novo Nordisk Pharma GmbH that includes: speaking and lecture fees. Reinhard Berner reports a relationship with Standing Committee on Vaccination (STIKO) that includes: board membership. Reinhard Berner reports a relationship with Standing Committee on Pandemic Respiratory Tract Infections at the RKI that includes: board membership. Reinhard Berner reports a relationship with Committee on Drug Safety and Drug Development for Children (KAKJ), Federal Insitute for Drugs and Medicinal Products (BfArM) that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Anti-viral action against type 1 diabetes autoimmunity: The GPPAD-AVAnT1A study protocol

Affiliations

Anti-viral action against type 1 diabetes autoimmunity: The GPPAD-AVAnT1A study protocol

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Research Materials