AbATE Follow-Up Study

Study Overview
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Brief Summary
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This study proposes to conduct a non-interventional, multi-center trial that will look at C-peptide results from one or two Mixed Meal Tolerance Tests (MMTT) in participants who received anti-CD3 treatment or placebo on the Abate ITN027AI trial. Anti-CD3 monoclonal antibody is a humanized antibody that is commonly used to prevent organ rejection. It was give in order to determine whether anti-CD3 mAb treatment can halt the progression of newly diagnosed type 1 diabetes. The overall hypothesis of this study is there will be less change in c-peptide levels of the previously treated group versus the control group.

Detailed Description
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We propose to conduct a non-interventional multi-center trial that will look at C-peptide results from one or two Mixed Meal Tolerance Tests (MMTT) in participants who received anti-CD3 treatment or placebo on the Abate ITN027AI trial. The first few subjects went on the trial late in 2005 and the last subjects were enrolled in 2009.The mixed meal tolerance tests will coincide with approximately 4 years and 6 years post ITN027AI study completion for each participant. Those participants, who completed the ITN027AI study in 2007 and 2008, will only have a single MMTT. We plan to enroll approximately 77 subjects at 5 sites who were previously active with ITN027AI.. Both the drug treated and the control group participants will be invited to participate. Along with Yale University these sites include, the University of California-San Francisco, University of Colorado-Barbara Davis, Benaroya Research Institute, and Pacific Northwest Research Institute -University of Washington. The investigators of each of these sites will be asked to contact their patients who were originally on the ITN027AI study. Subjects will be contacted via email or phone to see if they would be interested in participating on this Abate follow-up study. Eligible participants will come to the Yale University Church St. Research Unit or other participating ITN study site for either 1 or 2 mixed meal tolerance tests to determine their current c-peptide status. The available sites for participants to go to include: Yale University, University of California-San Francisco, University of Colorado-Barbara Davis Center, Benaroya Research Institute and Pacific Northwest-University of Washington. This first visit will consist of the following: an explanation of the study, an assessment of inclusion/exclusion criteria and documentation of informed consent. If the subject meets the inclusion/exclusion criteria, a complete medical history will be obtained, physical examination including vital signs, urine pregnancy test if a female of childbearing potential and an assessment of concomitant medications. The subject will then have a Mixed Meal Tolerance Tests (MMTT) with a possible 2nd MMTT with C-Peptide and glucose measurements a year later based on how long it has been since they were on the ITN027AI Study.The subject will also have a 4 hour urine collection for C-peptide and creatinine during this MMTT. If a repeat MMTT is done a year later then another 4 hour urine sample during the MMTT will be collected for C-peptide and Creatinine measurement.

Official Title
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ITN0127AI Autoimmunity-blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes (AbATE) Follow-Up Study

Conditions
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Diabetes Mellitus, Type 1

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior participation on either the treatment or the control arm of the Abate ITN027AI trial Signed Informed Consent Exclusion Criteria: Inability or unwillingness to give informed consent Participation in an investigational treatment trial within the last 6 weeks before enrollment Ongoing major systemic illness. Clinically active serious infections. Any medical condition that in the opinion of the investigator would interfere with safe completion of the trial. Positive pregnancy test in menstruating women Actively breast feeding

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 37 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 |
| --- | --- |
| Anti-CD3 mAb Plus Diabetes Standard of Care Group<br>This group of individuals received treatment in the original AbATE study. | |
| Diabetes Standard of Care Group<br>During the original AbATE study these individuals received standard care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mixed Meal Tolerance Test (MMTT) C-peptide levels | Labs will be obtained to assess beta cell function via c-peptide levels and glucose at 11 time points during the mixed meal tolerance test. Blood samples will be obtained prior to the start of the mixed meal tolerance test to assess auto-antibody status and HbA1c. Approximately 60 cc's of blood will also be obtained for PBMC's and future studies as related to the immunology and genetics of T1DM. A 4 hour urine sample during the MMTT will be collected for C-peptide and Creatinine measurement. We plan to determine the relationship between this measurement and the insulin secretory response. | 1 Study Day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety experience | To determine the safety experience and diabetes specific clinical parameters in previous participants in the ITN027 trial via the history of hospitalizations and other adverse events since the participants came of the original ITN027AI Treatment Trial. | 1 Study Day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T1D, type 1 diabetes, type 1 diabetes mellitus, juvenile diabetes, autoimmune diabetes, autoimmune, anti-CD3 mAb, mAb hOKT3g1(Ala-Ala), teplizumab