Diabetes Mellitus, Type 1, Hypoglycemia, Autoimmune Diseases, Diabetes Mellitus
Conditions
Brief summary
To assess whether there is a difference in endogenous insulin secretion, measured as stimulated C-peptide secretion (area under the curve during a 4-hour mixed meal tolerance test), at the 1 year visit, for study subjects receiving combinational therapy versus those receiving placebo. The study will also examine the effect of the proposed treatments on immunological outcomes, specifically proportion of regulatory T cells at the 1 year visit.
Interventions
2.5 mg/kg administered as two divided infusions of 0.5 mg/kg and 2 mg/kg on Days 1 and 2.
DRUGInterleukin 2
1 million IU per dose administered subcutaneously for 5 consecutive days on Days 10-14, and then every two weeks.
DRUGExenatide
2 mg administered subcutaneously weekly for up to 52 weeks.
DRUGAdalimumab
50 mg administered subcutaneously once a month for 1 year.
OTHERATG Placebo
ATG placebo mimicking Thymoglobulin administered intravenously.
OTHERIL-2 Placebo
IL-2 placebo mimicking Aldesleukin administered subcutaneously.
OTHERAdalimumab Placebo
Placebo mimicking Adalimumab administered subcutaneously.
OTHERExenatide Placebo
Placebo mimicking Exenatide administered subcutaneously.
Sponsors
Diabetes Research Institute Foundation
Camillo Ricordi and Jay Skyler
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Patients must meet all of the following criteria to be eligible to participate in this study: 1. Subject must be able to understand and provide informed consent. 2. Males and females, 18-35 years of age. 3. New onset T1D for no longer than 120 days at the time of randomization. 4. Affected by T1D, according to ADA standard criteria, and confirmed by positivity of at least one T1D-associated autoantibody, to GAD65, IA-2, ZnT8, or insulin autoantibodies (if patient has been treated with insulin for less than 2 weeks). 5. Being on insulin therapy. 6. Stimulated C-peptide peak level \>0.2 nmol/L at the baseline 1 visit MMTT. 7. Female subjects of childbearing potential must have a negative pregnancy test upon study entry. 8. Female (and male) subjects with reproductive potential must agree to use two FDA approved methods of birth control for the entire duration of the study. 9. Adequate venous access to support study required blood draws.
Exclusion criteria
* Potential participants must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Simulated C-peptide AUC | 1 Year Visit | Endogenous insulin secretion as measured as stimulated C-peptide section Area Under the Curve (AUC) during a 4 hour mixed meal tolerance test (MMTT) |
| Proportion of regulatory T cells | 1 Year Visit | As measured from blood samples |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1c (HbA1c) levels | Up to 18 months | Measure of glycemic control as evaluated by HbA1c levels from blood samples |
| Insulin dose | Up to 18 months | Measure of glycemic control as evaluated by insulin dose |
| Mean daily plasma glucose levels | Up to 18 months | Measure of glycemic control as evaluated by the mean daily plasma glucose levels from blood samples |
| Incidence of immune response adverse events | Up to 18 months | Incidence of immune response adverse events as assessed by treating physician |
Outcome results
None listed