Type 1 Diabetes Extension Study

Study Overview
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Brief Summary
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This is a multi-center, prospective, non-interventional study that focuses on the long- term effects following participation in selected ITN new-onset Type1 Diabetes Mellitus studies with immunomodulatory agents (T1DM, T1D). This observational study will: follow participants to determine how long they continue to produce insulin, and will also assess how changes in the immune system over time relate to the ability to produce insulin. This information could help design better therapies for type 1 diabetes in the future.

Detailed Description
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Depending upon a participant's level of insulin production, participation may be as short as one return visit or a maximum of five years. Evaluation visits will include: Overall health assessments Blood and urine collections Mixed meal tolerance test (MMTTs) for certain participants, per protocol.

Official Title
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Type 1 Diabetes Extension Study

Conditions
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Type 1 Diabetes Mellitus, T1DM, T1D

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior participant in an Immune Tolerance Network (ITN) executive committee approved T1DM study. Ability to sign informed consent/assent (as applicable for children). Exclusion Criteria: Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial; or Inability to comply with the study visit schedule and required assessments.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 35 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1: Detectable C-peptide by MMTT<br>Participants with detectable C-peptide at their: Last Immune Tolerance Network (ITN) T1DM week 104 study visit, Last AbATE (NCT00129259) follow-up visit, or Last ITN066AI T1DES visit Detectable C-peptide is defined as a value above the lower limit of detection. | |
| Group 2:Undetectable C-peptide by MMTT<br>Participants without detectable C-peptide at their: Last ITN T1DM week 104 study visit, Last AbATE follow-up visit, or last ITN066AI T1DES visit Undetectable C-peptide is defined as a value below the lower limit of detection. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Beta Cell Function by MMTT-Stimulated Mean C-peptide Area Under the Curve (AUC) | Evaluation of changes in beta cell function over time will be measured by mixed-meal tolerance test (MMTT) -Stimulated mean C-Peptide area under the curve (AUC). C-peptide is released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. Detectable C-peptide is defined as any value during a MMTT of ≥0.15 ng/mL. | Baseline (Visit 0) to Month 60 (Year 5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin Use in Units per Kilogram Body Weight Per Day | The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity. | Baseline (Visit 0) to Month 60 (Year 5) | 
| Change in HbA1C | Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. | Baseline (Visit 0) to Month 60 (Year 5) | 
| Count of Participant-Reported Major Hypoglycemic Events | Major hypoglycemic events are defined as a glucose concentration <55 mg/dL (grades 2-5, NCI-CTCAE version 4.03), or clinically: involving seizure(s) or involving loss of consciousness (coma), or requiring assistance from another individual in order to recover. | Baseline (Visit 0) to Month 60 (Year 5) | 
| Time to Undetectable C-Peptide | To assess the longevity of beta cell function, time to undetectable C-peptide will be evaluated using Kaplan-Meier survival estimates. | Baseline (Visit 0) to Month 60 (Year 5) | 
| Frequency of Grade 3 or Higher Adverse Events (AEs) of Interest | Events of interest include but are not limited to: Opportunistic and serious infections Malignancy Cardiovascular disease Development of autoimmune disease(s) Hypersensitivity reactions to unrelated allergens Reference for Grade 3 or higher AEs: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 (June 14, 2010). | Baseline (Visit 0) to Month 60 (Year 5) | 
| Severity of Grade 3 or Higher Adverse Events (AEs) of Interest | Events of interest include but are not limited to: Opportunistic and serious infections Malignancy Cardiovascular disease Development of autoimmune disease(s) Hypersensitivity reactions to unrelated allergens Reference for Grade 3 or higher AEs: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 (June 14, 2010). | Baseline (Visit 0) to Month 60 (Year 5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin, Glucose Intolerance