Type 1 Diabetes MedDRA version: 21.1 Level: PT Classification code 10066284 Term: Diabetes prophylaxis System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Product Name: recombinant DNA-derived human insulin (rH-insulin): Zinc Insulin
Product Code: QA307X
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: INSULINA ZINCO UMANA DA DNA RICOMBINANTE
CAS
Sponsors
TRIALNET COORDINATING CENTER AT THE UNIVERSITY OF SOUTH FLORIDA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant in TrialNet Natural History/Pathway to Prevention Study (TN01) and thus, a relative of a proband with T1D and between the ages of 1-45 at the time of enrollment in TN01. 2. If most recent OGTT demonstrates Normal Glucose Tolerance, participants must be age =3 at time of randomization in this trial. 3. If most recent OGTT demonstrates Abnormal Glucose Tolerance, participants must be age 3-7 at time of randomization in this trial. 4. mIAA confirmed positive within the previous six months. 5. Participant must weigh =12 kg at the time of screening. 6. At least one other diabetes-associated autoantibody present on two separate samples, one of which was drawn within the past six months. Confirmation does not have to involve the same 2 autoantibodies. 7. Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the participant is =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Diagnosed with Diabetes or having their most recent OGTT with fasting glucose =126 mg/dl or 2 hour glucose = 200 mg/dl. 2. Prior participation in clinical research for secondary prevention of T1D. 3. History of treatment with insulin or oral hypoglycemic agent. 4. Current chronic use of medications altering stomach acid (such as H2 blockers, proton pump inhibitors and antacids). 5. History of gastric ulcer or gastric surgery. 6. History of therapy with immunosuppressive drugs or non-physiologic glucocorticoids within the past two years for a period of more than three months. 7. Has severe active disease, e.g. chronic active hepatitis, severe cardiac, pulmonary, renal, hepatic, immune deficiency and/or disease that is likely to limit life expectancy or lead to therapies such as immunosuppression during the time of the study. 8. Ongoing use of medications known to influence glucose tolerance, i.e. sulfonylureas, growth hormone, metformin, anticonvulsants, thiazide or potassium depleting diuretics, beta adrenergic blockers, niacin. Participants on such medications should be changed to a suitable alternative, if available, and will become eligible one month after medication is discontinued. 9. Pregnant, intends to become pregnant while on study, or lactating. 10. Deemed unlikely or unable to comply with the protocol or have any complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to assess the effects of varying doses and schedules of oral insulin on immunologic and metabolic markers in participants at risk for T1D.;Secondary Objective: Not Applicable;Primary end point(s): The primary outcome is the change in immune function as assessed by level or quality of T lymphocyte or autoantibody biomarkers of ß-cell specific immune response measured between 13 and 26 weeks after 1st dose versus baseline. Mechanistic assessments will consist of studies such as: o DNA for testing diabetes or other immune-associated genetic markers. o RNA for the evaluation of immune cell frequency and function by gene expression analysis o Peripheral Blood Mononuclear Cells (PBMCs) for the evaluation of immune cell function, especially antigen-specific responses relevant to the hypothesis that oral insulin can induce a state of tolerance to islet proteins o Serum and plasma for the evaluation of islet autoantibody epitope, affinity, isotyping and proteomics-based assessment of immune responses. o CBC with Differential Metabolic assessments will consist of: o Baseline OGTT (i.e. within 52 days of initiation of treatment), as well as OGTTs at the 6 month and 12 month visits. Glucose, insulin, C-peptide, and other analytes will be measured from OGTT samples. o Glucose, insulin, and C-peptide will be measured before the study drug dose, and at 1 and 2 hours after dosing during study visits V0(A), V0(B), V1. o HbA1c;Timepoint(s) of evaluation of this end point: Immune function can be assessed through multiple (often correlated) markers as well as additional cytokine/inflammation/genetic markers; however, our primary outcome is the change in immune function as assessed by level or quality of T lymphocyte or autoantibody biomarkers of ß-cell specific immune response measured between 13 and 26 weeks after 1st dose versus baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In a secondary manner, we will also evaluate multiple additional immunologic markers, such as phenotypic markers: na¿ve, effector memory, and central memory CD4+ T cells and CD8+ T cells as well as regulatory T cells. These markers will be measured as absolute numbers per mL, and will be assessed at baseline (i.e. prior to oral insulin treatment) as well as at multiple timepoints during and after treatment (Appendix A). Given that our focus is on how these oral insulin regimens affect immune cell mobilization and thus a response by the immune system, we will assess the fold change at the various timepoints (i.e. the ratio of the post-treatment level to the baseline marker levels). Secondary endpoints will also include clinical responses to treatment as measured by metabolic markers before and after treatment. C-peptide levels along with insulin and glucose levels before and after treatment will be captured and evaluated to better characterize these participants, particularly in relation to changes in immune markers.;Timepoint(s) of evaluation of this end point: ongoing | — |
Countries
Australia, Canada, European Union, Finland, Germany, Italy, Sweden, United Kingdom, United States
Contacts
Public ContactJulie Martin
TrialNet Coordinating Center
Outcome results
None listed