TODAY2 Phase 1 Immediate Post-Intervention Observational Follow-up Study (T2P1)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2 in Obese
• Intervention / Treatment: Other: standard of care in general clinical practice

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 550

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University
  • Maryland
    • Rockville, Maryland, United States, 20852
      • George Washington University Biostatistics Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Diabetes Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Syracuse, New York, United States, 13214
      • State University of New York Upstate Medical University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 22 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

participants in the TODAY clinical trial

Description

Inclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TODAY cohort; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Sonia Caprio, MD, Yale University; Principal Investigator: Silva Arslanian, MD, University of Pittsburgh; 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 School of Medicine; Study Chair: Phil Zeitler, MD PhD, University of Colorado, Denver; Principal Investigator: Kathryn Hirst, PhD, George Washington University

Publications and helpful links

General Publications

• TODAY Study Group. Postintervention Effects of Varying Treatment Arms on Glycemic Failure and beta-Cell Function in the TODAY Trial. Diabetes Care. 2021 Jan;44(1):75-80. doi: 10.2337/dc20-0622. Epub 2020 Nov 10.
• TODAY Study Group, Shah RD, Braffett BH, Tryggestad JB, Hughan KS, Dhaliwal R, Nadeau KJ, Levitt Katz LE, Gidding SS. Cardiovascular risk factor progression in adolescents and young adults with youth-onset type 2 diabetes. J Diabetes Complications. 2022 Mar;36(3):108123. doi: 10.1016/j.jdiacomp.2021.108123. Epub 2022 Jan 3.
• Trief PM, Uschner D, Tung M, Marcus MD, Rayas M, MacLeish S, Farrell R, Keady J, Chao L, Weinstock RS. Diabetes Distress in Young Adults With Youth-Onset Type 2 Diabetes: TODAY2 Study Results. Diabetes Care. 2022 Mar 1;45(3):529-537. doi: 10.2337/dc21-1689.
• TODAY Study Group, Bjornstad P, Drews KL, Caprio S, Gubitosi-Klug R, Nathan DM, Tesfaldet B, Tryggestad J, White NH, Zeitler P. Long-Term Complications in Youth-Onset Type 2 Diabetes. N Engl J Med. 2021 Jul 29;385(5):416-426. doi: 10.1056/NEJMoa2100165.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: May 24, 2011
• First Submitted That Met QC Criteria: June 1, 2011
• First Posted (Estimate): June 2, 2011

Study Record Updates

• Last Update Posted (Actual): August 4, 2021
• Last Update Submitted That Met QC Criteria: July 28, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: pediatrics; complications; type 2 diabetes mellitus; metformin; post-intervention study
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: DK61230-T2P1