Primary Intervention With Mucosal Insulin

Primary Intervention With Mucosal Insulin for Prevention of Type 1 Diabetes in Infants at High Genetic Risk to Develop Diabetes POINT (Primary Oral Insulin Trial) A Dose Finding and Safety Study ( Pre-POINT )

A dose with proven drug bioavailability to the immune system for use in a phase II/III primary T1DM (type 1 diabetes) vaccination trial (POINT study) in genetically at risk subjects.

Study Design Randomized, placebo-controlled, double-blind/double-masked, multi-center, dose escalation primary intervention pilot study.

Accrual Objective 25 (3:2 randomization to active and control arms)

The objective of this study is to determine the feasibility, safety and bioavailability of oral insulin in children with high genetic risk for T1DM in a dose escalation primary intervention pilot study.

Inclusion Criteria:

1. Children aged 2 years to 7 years who:

   • Have a multiplex first degree family history of T1DM (both parents, parent and sib, or two sibs);
   • Type 1 diabetes susceptible HLA DR4-DQB1*0302 or DR4-DQB1*0304 haplotype and

   None of the following HLA DR or DQB1 alleles:

   • DR 11
   • DR 12
   • DQB1*0602
   • DR7-DQB1*0303
   • DR14-DQB1*0503 or
   • Have a sibling with T1DM;
   • Identical by descent for the HLA DR3/DR4-DQ8 genotype with their diabetic sibling;

2. Islet autoantibody negative at time of recruitment.

Exclusion Criteria:

1. Children with any kind of congenital or acquired chronic disease that potentially interfere with the study objectives.
2. Prior or current participation in another intervention trial.
3. Chronic oral steroid use and/or other chronic oral immunosuppressant