BMJ Open (Nov 2021)

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

  • Matthew D Snape,
  • Melanie Gündert,
  • Anette-Gabriele Ziegler,
  • Peter Achenbach,
  • Reinhard Berner,
  • Kristina Casteels,
  • Thomas Danne,
  • Joerg Hasford,
  • Olga Kordonouri,
  • Karin Lange,
  • Helena Elding Larsson,
  • Markus Lundgren,
  • Agnieszka Szypowska,
  • John A Todd,
  • Ezio Bonifacio,
  • Nicole Zubizarreta,
  • Christiane Winkler,
  • Åke Lernmark,
  • Daniel Agardh,
  • Cigdem Gezginci,
  • Claudia Ramminger,
  • Marlon Scholz,
  • Katharina Warncke,
  • Carin Andrén Aronsson,
  • Rasmus Bennet,
  • Lina Fransson,
  • Helena Elding Larsson,
  • Zeliha Mestan,
  • Caroline Nilsson,
  • Anita Ramelius,
  • Carina Törn,
  • Sarah Hogg,
  • Catherine Owen,
  • Lidia Groele,
  • Florian Haupt,
  • Claudia Matzke,
  • Robin Assfalg,
  • Matthew Snape,
  • Felix Reschke,
  • Marcin L Pekalski,
  • Andreas Weiss,
  • Andrew Johnston,
  • Manja Jolink,
  • Loredana Marcovecchio,
  • Mariusz Ołtarzewski,
  • Stefanie Arnolds,
  • Annika Kölln,
  • Markus Pfirrmann,
  • Corinna Barz,
  • Karina Blasius,
  • Nadine Friedl,
  • Adriano Gomez-Bantel,
  • Martin Heigermoser,
  • Bianca Höfelschweiger,
  • Nadine Klein,
  • Ramona Lickert,
  • Rebecca Niewöhner,
  • Katharina Schütte-Borkovec,
  • Mira Taulien,
  • Lara Vogel,
  • Franziska Voß,
  • José Maria Zapardiel Gonzalo,
  • Philipp Sifft,
  • Heidi Kapfelsberger,
  • Merve Vurucu,
  • Katharina Sarcletti,
  • Stefanie Jacobson,
  • Yulia Grinin,
  • John A. Todd,
  • Anette-G. Ziegler,
  • Marcin L. Pekalski,
  • Anette G. Ziegler,
  • Annre Rochtus,
  • An Jacobs,
  • Hilde Morobé,
  • Jasmin Paulus,
  • Brontë Vrancken,
  • Natalie Van den Driessche,
  • Renka Van Heyste,
  • Janne Houben,
  • Veerle Vanhuyse,
  • Sevina Dietz,
  • Gita Gemulla,
  • Manja Gottschalk-Schwarz,
  • Sophie Heinke,
  • Angela Hommel,
  • Susann Kowal,
  • Fabian Lander,
  • Robert Morgenstern,
  • Marc Weigelt,
  • Sari Arabi,
  • Raphael Hoffmann,
  • Ruth Blechschmidt,
  • Franziska Ehrlich,
  • Anja Loff,
  • Laura Galuschka,
  • Ute Holtkamp,
  • Nils Janzen,
  • Sarah Landsberg,
  • Erika Marquardt,
  • Frank Roloff,
  • Kerstin Semler,
  • Thekla von dem Berge,
  • Melanie Bunk,
  • Simone Färber-Meisterjahn,
  • Willi Grätz,
  • Ines Greif,
  • Melanie Herbst,
  • Anna Hofelich,
  • Benjamin Marcus,
  • Annette Munzinger,
  • Jasmin Ohli,
  • Franziska Reinmüller,
  • Tiziana Welzhofer,
  • Sylwia Dybkowska,
  • Katarzyna Dżygało,
  • Dorota Owczarek,
  • Katarzyna Popko,
  • Agnieszka Skrobot,
  • Anna Taczanowska,
  • Beata Zduńczyk,
  • Charlotte Brundin,
  • Ida Jönsson,
  • Sara Maroufkhani,
  • Evelyn Tekum Amboh,
  • Katarzyna Gajewska-Knapik,
  • Elena Romero,
  • Suzannah Twiss,
  • Helen Gallon,
  • Laura Gebbie,
  • Fiona Jenkinson,
  • Steven Pratt,
  • Steve Robson,
  • Claire Simmister,
  • Evelyn Thomson,
  • Eileen Walton

DOI
https://doi.org/10.1136/bmjopen-2021-052449
Journal volume & issue
Vol. 11, no. 11

Abstract

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Introduction The 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 analysis Infants 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 dissemination The 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 number NCT04769037.