Type 1 Diabetes
Conditions
Keywords
Type 1 Diabetes, Diabetes, Autoimmune Diabetes
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.
Interventions
DRUGHuman Insulin
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)
OTHEROral Placebo
Oral Placebo is given orally daily
Sponsors
University Hospital Dresden
Diabetes Research Institute, Munich, Germany.
University of Bristol
Juvenile Diabetes Research Foundation
German Federal Ministry of Education and Research
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 7 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood Glucose Levels | Day 1 | 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. |
| Daily Evaluation of Blood Glucose Levels | Days 2 through 7 | Blood glucose will be measured 60 minutes after the administration of the Insulin. |
| Evaluation of Blood Glucose Levels | Measured 60 minutes after oral insulin dosing, every day during each 4th week, as long as the subject is given oral insulin. | After treatment day 7, Insulin will be administered and measured on a monthly basis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total IgE and IgE. | 2 weeks, 3 months, 6 months | 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. |
| T-cell responses related to potential immune response to Insulin | Day 1, 15 days, 3 and 6 months. | 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. |
Countries
United States
Outcome results
None listed