Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jun 28;9(6):e028578.
doi: 10.1136/bmjopen-2018-028578.

Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol

Anette-Gabriele Ziegler  1   2 , Peter Achenbach  1   2 , Reinhard Berner  3 , Kristina Casteels  4   5 , Thomas Danne  6 , Melanie Gündert  1 , Joerg Hasford  7 , Verena Sophia Hoffmann  1 , Olga Kordonouri  6 , Karin Lange  8 , Helena Elding Larsson  9   10 , Markus Lundgren  9 , Matthew D Snape  11   12 , Agnieszka Szypowska  13 , John A Todd  14 , Ezio Bonifacio  15 ; GPPAD Study group
Affiliations

Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol

Anette-Gabriele Ziegler et al. BMJ Open. .

Abstract

Introduction: The POInT study, an investigator initiated, randomised, placebo-controlled, double-blind, multicentre primary prevention trial is conducted to determine whether daily administration of oral insulin, from age 4.0 months to 7.0 months until age 36.0 months to children with elevated genetic risk for type 1 diabetes, reduces the incidence of beta-cell autoantibodies and diabetes.

Methods and analysis: Infants aged 4.0 to 7.0 months from Germany, Poland, Belgium, UK and Sweden are eligible if they have a >10.0% expected risk for developing multiple beta-cell autoantibodies as determined by genetic risk score or family history and human leucocyte antigen genotype. Infants are randomised 1:1 to daily oral insulin (7.5 mg for 2 months, 22.5 mg for 2 months, 67.5 mg until age 36.0 months) or placebo, and followed for a maximum of 7 years. Treatment and follow-up is stopped if a child develops diabetes. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies or diabetes. Other outcomes are: (1) Any persistent confirmed beta-cell autoantibody (glutamic acid decarboxylase (GADA), IA-2A, autoantibodies to insulin (IAA) and zinc transporter 8 or tetraspanin 7), or diabetes, (2) Persistent confirmed IAA, (3) Persistent confirmed GADA and (4) Abnormal glucose tolerance or diabetes.

Ethics and dissemination: The study is approved by the ethical committees of all participating clinical sites. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the trial.

Trial registration number: NCT03364868.

Keywords: clinical trials; general diabetes; paediatric endocrinology.

PubMed Disclaimer

Conflict of interest statement

Competing interests: Matthew Snape has received research grants paid to his institution for work as an investigator on clinical trials from the GSK group of companies, Pfizer, Janssen, Novavax, MedImmune, Alios BioPharma and Ablynx. He has also received support for travel and accommodation to attend international conferences from GSK group of companies, and, prior to 2017, received support paid to his institution as a member of the advisory board for Sanofi-Pasteur MSD and as a consultant for MedImmune.

Figures

Figure 1
Figure 1
POInT study flow and time schedule for a participant with maximum follow-up of 54 months. * p. BL: post baseline visit, ** Call: interim telephone calls with families to asses adverse events and support trial adherence. mo, months; POInT, Primary Oral Insulin Trial.
See this image and copyright information in PMC

References

    1. Ziegler AG, Bonifacio E, BABYDIAB-BABYDIET Study Group. Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia 2012;55:1937–43. 10.1007/s00125-012-2472-x - DOI - PubMed
    1. Kimpimäki T, Kulmala P, Savola K, et al. . Natural history of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 2002;87:4572–9. 10.1210/jc.2002-020018 - DOI - PubMed
    1. Krischer JP, Lynch KF, Schatz DA, et al. . The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia 2015;58:980–7. 10.1007/s00125-015-3514-y - DOI - PMC - PubMed
    1. Ziegler AG, Rewers M, Simell O, et al. . Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 2013;309:2473–9. 10.1001/jama.2013.6285 - DOI - PMC - PubMed
    1. Bonifacio E. Predicting type 1 diabetes using biomarkers. Diabetes Care 2015;38:989–96. 10.2337/dc15-0101 - DOI - PubMed

Publication types

Associated data