Immune Effects of Oral Insulin in Relatives at Risk for Type 1 Diabetes Mellitus (TN20)

Study Overview
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Brief Summary
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The study is a 2 arm, multi-center, randomized, open-labeled clinical trial designed to assess the effects of varying doses and schedules of oral insulin on immunological and metabolic markers in relatives at risk for type 1 diabetes (T1D).

Detailed Description
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A minimum of 40 eligible participants will be identified for study participation from the TrialNet Pathway to Prevention study. Participants must have a relative with type 1 diabetes and be positive for insulin autoantibodies and at least one other autoantibody. All participants will receive active treatment of recombinant insulin treatment in capsules of either 67.5 mg daily or 500mg every other week. Participants will need to visit the study site up to eleven times over one year for blood tests and other study procedures. During the beginning treatment phase there are two visits one month apart for those given the 67.5 mg dose, and three visits two weeks apart to titrate the dose for those in the 500mg treatment group. There are three additional treatment visits at months 2, 3, and 6 and 4 additional visits for follow-up at months 7, 8, 9 and 12. The primary outcome is the change in immune function as assessed by change in level or quality of T lymphocyte or autoantibody biomarkers measured between 13 and 26 weeks compared to baseline. .

Official Title
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Exploring Immunologic Effects of Oral Insulin in Relatives at Risk for Type 1

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: 67.5 mg oral insulin crystals daily
* Drug: 500mg oral insulin crystals every other week


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants in TrialNet Natural History/Pathway to Prevention Study (TN01); is relative of proband with type 1 diabetes Between ages 3-45 with normal Oral Glucose Tolerance Test (OGTT) or between ages 3-7 with an abnormal OGTT Confirmed positive for insulin autoantibodies within previous six months Confirmed positive for one or more other autoantibodies on two separate occasions within the past six months Exclusion Criteria: Diagnosed with type 1 diabetes History of treatment with insulin or oral hypoglycemic agent History of therapy with immunosuppressive drugs or non-physiologic glucocorticoids within the past two years for a period of more than three months Ongoing use of medications known to influence glucose tolerance Pregnant or intending to become pregnant while on study or lactating

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 67.5 mg oral insulin crystals daily<br>67.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months | Drug: 67.5 mg oral insulin crystals daily<br>* human insulin crystals in capsules<br>* Other names: Humulin R crystals;|
| Experimental: 500mg oral insulin crystals every other week<br>500 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given every other week for six months | Drug: 500mg oral insulin crystals every other week<br>* human insulin crystals in capsules<br>* Other names: Humulin R crystals;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in GAD65 Autoantibody Titer (DK Units/mL) | Change in T-lymphocyte (GAD65) biomarker of beta cell specific immune response | 13 and 26 weeks after first dose versus baseline | 
| Change in mIAA Autoantibody Titer From Baseline | Micro-islet autoantibodies (mIAA) autoantibody titers are a measure of of beta cell immune response | 13 and 26 weeks after first dose versus baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oral insulin