Supplementation with Bifidobacterium longum subspecies infantis EVC001 for mitigation of type 1 diabetes autoimmunity: the GPPAD-SINT1A randomised controlled trial protocol

IntroductionThe Global Platform for the Prevention of Autoimmune Diabetes-SINT1A Study is designed as a randomised, placebo-controlled, double-blind, multicentre, multinational, primary prevention study aiming to assess whether daily administration of Bifidobacterium infantis from age 7 days to 6 we...

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Published in:	BMJ open Vol. 11; no. 11; p. e052449
Main Authors:	Ziegler, Anette-Gabriele, Berner, Reinhard, Elding Larsson, Helena, Gündert, Melanie, Lundgren, Markus, Oltarzewski, Mariusz, Pfirrmann, Markus, Snape, Matthew D, Todd, John A, Haupt, Florian, Assfalg, Robin, Blasius, Karina, Friedl, Nadine, Höfelschweiger, Bianca, Jolink, Manja, Klein, Nadine, Niewöhner, Rebecca, Schütte-Borkovec, Katharina, Taulien, Mira, Vogel, Lara, Voß, Franziska, Weiß, Andreas, Zapardiel Gonzalo, José Maria, Sifft, Philipp, Vurucu, Merve, Sarcletti, Katharina, Jacobson, Stefanie, Grinin, Yulia, Todd, John A., Ziegler, Anette-G., Achenbach, Peter, Kordonouri, Olga, Snape, Matthew, Szypowska, Agnieszka, Warncke, Katharina, Larsson, Helena Elding, Ziegler, Anette G., Jacobs, An, Morobé, Hilde, Paulus, Jasmin, Vrancken, Brontë, Houben, Janne, Vanhuyse, Veerle, Gottschalk-Schwarz, Manja, Hommel, Angela, Morgenstern, Robert, Weigelt, Marc, Zubizarreta, Nicole, Arabi, Sari, Hoffmann, Raphael, Blechschmidt, Ruth, Danne, Thomas, Galuschka, Laura, Holtkamp, Ute, Janzen, Nils, Landsberg, Sarah, Reschke, Felix, Semler, Kerstin, Berge, Thekla von dem, Greif, Ines, Herbst, Melanie, Marcus, Benjamin, Munzinger, Annette, Ramminger, Claudia, Reinmüller, Franziska, Welzhofer, Tiziana, Winkler, Christiane, Ołtarzewski, Mariusz, Dżygało, Katarzyna, Groele, Lidia, Owczarek, Dorota, Popko, Katarzyna, Skrobot, Agnieszka, Taczanowska, Anna, Zduńczyk, Beata, Agardh, Daniel, Bennet, Rasmus, Brundin, Charlotte, Fransson, Lina, Maroufkhani, Sara, Mestan, Zeliha, Ramelius, Anita, Amboh, Evelyn Tekum, Törn, Carina, Marcovecchio, Loredana, Gajewska-Knapik, Katarzyna, Hogg, Sarah, Twiss, Suzannah, Owen, Catherine, Gallon, Helen, Gebbie, Laura, Pratt, Steven, Robson, Steve, Simmister, Claire, Thomson, Evelyn, Walton, Eileen, Johnston, Andrew
Format:	Journal Article
Language:	English
Published:	England British Medical Journal Publishing Group 09-11-2021 BMJ Publishing Group LTD BMJ Publishing Group
Series:	Protocol
Subjects:	Age Antigens Autoimmunity Bacteria Bifidobacterium longum subspecies infantis Child Diabetes diabetes & endocrinology Diabetes and Endocrinology Diabetes Mellitus, Type 1 - prevention & control Dietary Supplements Epidemiology Fatty acids Gastrointestinal Microbiome general diabetes Health risk assessment Humans immunology Infant Inflammation Insulin Laboratories Microbiota Multicenter Studies as Topic paediatrics Pediatrics Probiotics Randomized Controlled Trials as Topic Vaccines paediatrics epidemiology general diabetes immunology diabetes & endocrinology
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Summary:	IntroductionThe Global Platform for the Prevention of Autoimmune Diabetes-SINT1A Study is designed as a randomised, placebo-controlled, double-blind, multicentre, multinational, primary prevention study aiming to assess whether daily administration of Bifidobacterium infantis from age 7 days to 6 weeks until age 12 months to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies in childhood.Methods and analysisInfants aged 7 days to 6 weeks from Germany, Poland, Belgium, UK and Sweden are eligible for study participation if they have a >10.0% expected risk for developing multiple beta-cell autoantibodies by age 6 years as determined by genetic risk score or family history and HLA genotype. Infants are randomised 1:1 to daily administration of B. infantis EVC001 or placebo until age 12 months and followed for a maximum of 5.5 years thereafter. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies. Secondary outcomes are (1) Any persistent confirmed beta-cell autoantibody, defined as at least one confirmed autoantibody in two consecutive samples, including insulin autoantibodies, glutamic acid decarboxylase, islet tyrosine phosphatase 2 or zinc transporter 8, (2) Diabetes, (3) Transglutaminase autoantibodies associated with coeliac disease, (4) Respiratory infection rate in first year of life during supplementation and (5) Safety. Exploratory outcomes include allergy, antibody response to vaccines, alterations of the gut microbiome or blood metabolome, stool pH and calprotectin.Ethics and disseminationThe study was approved by the local ethical committees of the Technical University Munich, Medical Faculty, the Technische Universität Dresden, the Medizinische Hochschule Hannover, the Medical University of Warsaw, EC Research UZ Leuven and the Swedish ethical review authority. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the study.Trial registration numberNCT04769037.
Bibliography:	Protocol ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23
ISSN:	2044-6055 2044-6055
DOI:	10.1136/bmjopen-2021-052449