TODAY2 Phase 1 Immediate Post-Intervention Observational Follow-up Study

Study Overview
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Brief Summary
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The purpose of this study is to continue to follow participants in the TODAY clinical trial as they transition to non-blinded, non-randomized standard diabetes care and management with monitoring and follow-up for up to 24 months (phase 1), during which time the TODAY data are analyzed and findings interpreted to develop a long-term observational protocol (phase 2). Data are collected during phase 1 for descriptive purposes; there is no primary hypothesis.

Detailed Description
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TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multi-center study of the optimal approach to treatment of type 2 diabetes (T2D) in children and adolescents. The TODAY clinical trial of experimental interventions ended in February 2011. It is followed by TODAY2, a longitudinal study to continue the care and observation of the TODAY cohort beyond the end of the TODAY intervention trial. TODAY2 consists of two phases. First is the immediate transition of TODAY participants to non-blinded, non-randomized standard diabetes care and management with monitoring and follow-up for up to 24 months. During this period, the findings of TODAY are analyzed and interpreted by the study group. The second phase is a protocol for long-term longitudinal follow-up of the TODAY cohort, based on findings from TODAY. The primary objective of the first phase of TODAY2 is to continue to follow the TODAY subjects for up to 24 months in order to begin to: understand the persistence of the effects of the different treatment regimens used in TODAY, describe the continued evolution of beta cell function, and describe the development of vascular complications and risk factors for complications.

Official Title
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TODAY2 Phase 1 Immediate Post-Intervention Observational Follow-up Study of the TODAY Clinical Trial Cohort

Conditions
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Diabetes Mellitus Type 2 in Obese

Intervention / Treatment
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* Other: standard of care in general clinical practice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participated in the TODAY clinical trial. Provided informed consent to participate in T2P1.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 24 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 |
| --- | --- |
| TODAY cohort<br>The cohort of participants diagnosed with type 2 diabetes ages 10 to <18 and obese at time of diagnosis who participated in the TODAY clinical trial are recruited, consented and followed. | Other: standard of care in general clinical practice<br>* Participants consenting to receive study-provided care may be treated with metformin, insulin, statin, and ace-inhibitor, as needed for glycemic control and for comorbid conditions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effects of TODAY treatment assignment on long-term glycemic control | The primary objective of the first phase of TODAY2 is to begin to examine the persistence of effects of the TODAY treatment assignment on long-term glycemic control following discontinuation of randomized treatment. During this period, results of TODAY are produced and used to define additional outcomes for the second phase of TODAY2. | observed for 2 years in phase 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glycemic control | HbA1c is the designated measure of glycemic control during T2P1. Mean HbA1c levels for participants from the three original TODAY treatment arms are compared as measures of the degree and durability of glycemic control after discontinuation of initial randomized therapy. The overall target is to maintain HbA1c levels as close to the normal range as possible in order to reduce long-term diabetes complications. TODAY2 continues to use HbA1c < 6% as the target. | observed for 2 years in phase 1 | 
| safety | In TODAY2, subjects are treated with approved medications, i.e., metformin and/or insulin. No specific abnormalities are expected to develop in this cohort, given the well-documented safety record of these agents. However, abnormalities in laboratory tests (hemoglobin/hematocrit, liver function tests, calculated creatinine clearance), episodes of severe hypoglycemia, and incidence of side effects (e.g., gastrointestinal complaints) are tracked. | observed for 2 years in phase 1 | 
| insulin sensitivity and secretion | An important component of TODAY2 is to continue to monitor insulin sensitivity and secretion in the TODAY cohort after discontinuation of randomized therapy to determine (1) the evolution of changes in insulin secretion and sensitivity as participants emerge from puberty and enter young adulthood and (2) the effect of each of the initial therapies on the progression of changes in insulin sensitivity and secretion. Insulin sensitivity and secretion are determined with fasting glucose, insulin, C-peptide, and proinsulin levels, OGTT-based indices, HOMA, and QUICKI measured annually. | observed for 2 years in phase 1 | 
| cardiovascular risk factors | Both traditional and non-traditional CVD risk factors are measured in the first phase of TODAY2 and assessed overall as well as compared across initial treatment arms. Blood pressure is measured at every visit and specimens drawn annually for repeated measurements of lipids (free fatty acids, lipoprotein subclass levels, average LDL particle density, and total apoB level), fibrinogen, c-reactive protein, plasminogen activator inhibitor-1, homocysteine (vitamin B-12 to evaluate homocysteine levels), and interleukin-6. | observed for 2 years in phase 1 | 
| microvascular complications | Quantitation of microalbuminuria is performed by obtaining spot urine measurements of microalbumin/creatinine ratio at annual visits. Abnormal values are confirmed with two additional samples within three months; diagnosis of microalbuminuria is made as a result of two out of three positive tests. Creatinine clearance (by calculation) is determined at annual visits. The presence of peripheral neuropathy is evaluated using the Michigan Neuropathy Screening Instrument (MNSI) performed annually. | observed for 2 years in phase 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes mellitus, pediatrics, post-intervention study, metformin, complications