TODAY2 Phase 1 Immediate Post-Intervention Observational Follow-up Study (T2P1)
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.
Diabetes Mellitus Type 2 in Obese
Other: standard of care in general clinical practice
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||TODAY2 Phase 1 Immediate Post-Intervention Observational Follow-up Study of the TODAY Clinical Trial Cohort|
- effects of TODAY treatment assignment on long-term glycemic control [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: Yes ]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.
- glycemic control [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: Yes ]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.
- safety [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: Yes ]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.
- insulin sensitivity and secretion [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: No ]
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.
- cardiovascular risk factors [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: No ]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.
- microvascular complications [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: Yes ]
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.
Biospecimen Retention: Samples Without DNA
Blood and urine are collected on an annual basis and sent to the Central Biospecimen Laboratory for analysis and storage.
Analyses performed on an annual basis are: HbA1c, insulin sensitivity and secreation (fasting glucose, insulin, C-peptide, and proinsulin), 2-hour OGTT, pancreatic autoimmunity, serum creatinine, liver function tests, lipids (LDL, triglycerides, free fatty acids, lipoprotein subclass levels, average LDL particle density, and total apoB levels), cardiovascular risk factors (fibrinogen, c-reactive protein, homocysteine vitamin B-12, plasminogran activator inhibitor-1, interleukin-6), microalbumin.
HbA1c is also analyzed quarterly.
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||February 2014|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
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
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01364350
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|United States, Colorado|
|University of Colorado Denver|
|Denver, Colorado, United States, 80262|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06519|
|United States, Maryland|
|George Washington University Biostatistics Center|
|Rockville, Maryland, United States, 20852|
|United States, Massachusetts|
|Joslin Diabetes Center|
|Boston, Massachusetts, United States, 02215|
|Massachusetts General Hospital Diabetes Center|
|Boston, Massachusetts, United States, 02114|
|United States, Missouri|
|Saint Louis University|
|St Louis, Missouri, United States, 63104|
|St Louis, Missouri, United States, 63110|
|United States, New York|
|Columbia University Medical Center|
|New York City, New York, United States, 10032|
|State University of New York Upstate Medical University|
|Syracuse, New York, United States, 13214|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center|
|Oklahoma City, Oklahoma, United States, 73117|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|University of Texas Health Science Center at San Antonio|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||Silva Arslanian, MD||Children's Hospital of Pittsburgh|
|Principal Investigator:||Sonia Caprio, MD||Yale University|
|Principal Investigator:||Leona Cuttler, MD||CWRU Rainbow Babies and Children's Hospital|
|Principal Investigator:||Ken Copeland, MD||University of Oklahoma Health Science Center|
|Principal Investigator:||Mitch Geffner, MD||Children's Hospital Los Angeles|
|Principal Investigator:||Robin Goland, MD||Columbia University Naomi Berrie Diabetes Center|
|Principal Investigator:||Lorraine Katz, MD||Children's Hospital of Philadelphia|
|Principal Investigator:||Lori Laffel, MD||Joslin Diabetes Center|
|Study Director:||Barbara Linder, MD PhD||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Principal Investigator:||Jane Lynch, MD||The University of Texas Health Science Center at San Antonio|
|Principal Investigator:||Siripoom McKay, MD||Baylor College of Medicine|
|Principal Investigator:||David Nathan, MD||Massachusetts General Hospital|
|Principal Investigator:||Sherida Tollefsen, MD||Saint Louis University Health Sciences Center|
|Principal Investigator:||Ruth Weinstock, MD PhD||State University of New York - Upstate Medical University|
|Principal Investigator:||Neil White, MD||Washington University Early Recognition Center|
|Study Chair:||Phil Zeitler, MD PhD||University of Colorado, Denver|
|Principal Investigator:||Kathryn Hirst, PhD||George Washington University|