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

Diabetes Mellitus Type 2 in Obese Clinical Trial

— T2P1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01364350
• Other study ID #: DK61230-T2P1
• Status: Completed
• Start date: March 2011
• Est. completion date: February 2014

Study information

• Verified date: July 2021
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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. 1. 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. 2. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 550
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 24 Years

Eligibility

Inclusion Criteria:

• Participated in the TODAY clinical trial.
• Provided informed consent to participate in T2P1.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 2 in Obese
• Diabetes Mellitus, Type 2

Intervention

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.

Locations

Country	Name	City	State
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	Massachusetts General Hospital Diabetes Center	Boston	Massachusetts
United States	Case Western Reserve University	Cleveland	Ohio
United States	University of Colorado Denver	Denver	Colorado
United States	Baylor College of Medicine	Houston	Texas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	George Washington University Biostatistics Center	Rockville	Maryland
United States	Saint Louis University	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	State University of New York Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

TODAY Study Group. Postintervention Effects of Varying Treatment Arms on Glycemic Failure and ß-Cell Function in the TODAY Trial. Diabetes Care. 2021 Jan;44(1):75-80. doi: 10.2337/dc20-0622. Epub 2020 Nov 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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