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

Abstract

IntroductionThe 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 analysisInfants 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 disseminationThe 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 numberNCT03364868.

Birth and coming of age of islet autoantibodies

“…c). These include natural history studies such as TEDDY and primary prevention studies such as BABYDIET , TRIGR and POInT . The availability of high‐quality, high‐throughput and harmonized autoantibody tests mean that stable longitudinal measurements of the outcomes are possible.…”

Autoantigen Treatment in Type 1 Diabetes: Unsolved Questions on How to Select Autoantigen and Administration Route

“…This has been followed by further studies with that route of administration of the autoantigen to test giving oral insulin to very young children to prevent T1D [97]. The encouraging results with respect to safety and feasibility have led to a large ongoing trial [98,99].…”

Type 1 diabetes mellitus and its oral tolerance therapy

“…Benefited from these promising findings observed in this small pilot study, a larger phase 2 trial (ClinicalTrials.gov Identifier: NCT02547519) is underway. In addition, there are some clinical trials that are underway, such as Frida insulin intervention (ClinicalTrials.gov Identifier: NCT02620072) titled “Mechanistic Study Using Oral Insulin for Immune Efficacy in Secondary Prevention of Type 1 Diabetes” containing two insulin dose strengths (7.5 mg/d and 67.5 mg/d) and oral insulin therapy for prevention of autoimmune diabetes in infants (4 mo to 7 mo) with high genetic risk: the GPPAD-POInT (Global Platform of Autoimmune Diabetes-Primary Oral Insulin Trial, ClinicalTrials.gov Identifier: NCT03364868)[ 124 ].…”