Primary Intervention With Mucosal Insulin

Study Overview
=================
Brief Summary
-----------------
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)

Detailed Description
-----------------
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.

Official Title
-----------------
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 )

Conditions
-----------------
Type 1 Diabetes

Intervention / Treatment
-----------------
* Drug: Human Insulin
* Other: Oral Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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; Islet autoantibody negative at time of recruitment. Exclusion Criteria: Children with any kind of congenital or acquired chronic disease that potentially interfere with the study objectives. Prior or current participation in another intervention trial. Chronic oral steroid use and/or other chronic oral immunosuppressant

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 7 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Insulin<br>Oral Insulin at 2.5 mg, 7.5 mg, 22.5 mg, or 67.5 mg per day | Drug: Human Insulin<br>* There is a study drug dose increase once during the study. The dose increase will occur 6 months after entering into the study. A total of 6 children will be included at each dose (3 children will not have received insulin prior to entering the study and 3 children will have received a lower dose of insulin for 6 months). Further dose increases or more frequent dose increases in individual children will not be performed during Pre-POINT. Escalation will occur in both treatment and placebo group so that participants and study investigators will remain blinded to treatment throughout the study. First dose (2.5 mg oral insulin/day) Second dose (7.5 mg oral insulin/day) Third dose (22.5 mg oral insulin/day) Fourth dose (67.5 mg oral insulin/day)<br>* Other names: Oral Insulin;|
| Placebo Comparator: Placebo<br>Oral Placebo | Other: Oral Placebo<br>* Oral Placebo is given orally daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Blood Glucose Levels | Evaluation for hypoglycemia will be measured prior to administration of the insulin (baseline), then at 30, 60, and 120 minutes after administration of the insulin. | Day 1 | 
| Daily Evaluation of Blood Glucose Levels | Blood glucose will be measured 60 minutes after the administration of the Insulin. | Days 2 through 7 | 
| Evaluation of Blood Glucose Levels | After treatment day 7, Insulin will be administered and measured on a monthly basis. | Measured 60 minutes after oral insulin dosing, every day during each 4th week, as long as the subject is given oral insulin. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total IgE and IgE. | Allergy/intolerance to the study drug evaluated with total IgE and IgE antibodies to insulin at 2 weeks, 3 months, 6 months, then every 6 months thereafter, as well as monitored through self-reporting by families. Parents/guardians will be educated on and instructed to look out for possible allergic reactions to insulin. | 2 weeks, 3 months, 6 months | 
| T-cell responses related to potential immune response to Insulin | T-cell responses e.g. antibody and cell mediated immune results will be evaluated the day of administration then at 15 days, 3 and 6 months, and every 6 months of treatment, and will be reported directly to the Data Coordinating Center. | Day 1, 15 days, 3 and 6 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 1 Diabetes, Diabetes, Autoimmune Diabetes