TY - JOUR
T1 - Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk
T2 - The GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol
AU - Ziegler, Anette Gabriele
AU - Achenbach, Peter
AU - Berner, Reinhard
AU - Casteels, Kristina
AU - Danne, Thomas
AU - Gündert, Melanie
AU - Hasford, Joerg
AU - Hoffmann, Verena Sophia
AU - Kordonouri, Olga
AU - Lange, Karin
AU - Elding Larsson, Helena
AU - Lundgren, Markus
AU - Snape, Matthew D.
AU - Szypowska, Agnieszka
AU - Todd, John A.
AU - Bonifacio, Ezio
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
KW - clinical trials
KW - general diabetes
KW - paediatric endocrinology
UR - http://www.scopus.com/inward/record.url?scp=85068461302&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2018-028578
DO - 10.1136/bmjopen-2018-028578
M3 - Article
C2 - 31256036
AN - SCOPUS:85068461302
SN - 2044-6055
VL - 9
JO - BMJ Open
JF - BMJ Open
IS - 6
M1 - e028578
ER -