TODAY2 Phase 2 Follow-up (T2P2)

• ClinicalTrials.gov Identifier: NCT02310724
• Recruitment Status: Completed
• First Posted: December 8, 2014
• Last Update Posted: August 5, 2021
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Eye Institute (NEI)
• Information provided by (Responsible Party): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Tracking Information

• First Submitted Date: June 18, 2014
• First Posted Date: December 8, 2014
• Last Update Posted Date: August 5, 2021
• Actual Study Start Date: March 1, 2014
• Actual Primary Completion Date: January 17, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 29, 2016)

• diabetic retinopathy [ Time Frame: year 4 ]
  a microvascular complication determined by fundus photography
• microalbuminuria [ Time Frame: every 12 months ]
  a microvascular complication determined by urine albumin excretion >= 30 mg/day
• overt diabetic nephropathy [ Time Frame: every 12 months ]
  a microvascular complication determined by glomerular filtration rate < 70 mL/min/1.73m2
• peripheral diabetic neuropathy [ Time Frame: every 12 months ]
  a microvascular complication defined as the presence of Michigan Neuropathy Screening Instrument (MNSI) exam score >2 and <8 out of 10 appropriate responses to the Semmes-Weinstein monofilament (SW-MF) in either foot.
• cardiac function [ Time Frame: year 2 ]
  a macrovascular (cardiovascular) risk indicator determined by echocardiogram
• arterial stiffness [ Time Frame: year 5 ]
  a macrovascular (cardiovascular) risk indicator determined by pulse wave velocity
• cardiovascular risk lipid values [ Time Frame: every 12 months ]
  a macrovascular (cardiovascular) risk indicator determined by abnormal lipid value for LDL (>= 130 mg/dL) or triglycerides (>= 300 mg/dL)

Original Primary Outcome Measures (submitted: December 4, 2014)

• diabetic retinopathy [ Time Frame: year 4 ]
  a microvascular complication determined by fundus photography
• microalbuminuria [ Time Frame: annual ]
  a microvascular complication determined by urine albumin excretion >= 30 mg/day
• overt diabetic nephropathy [ Time Frame: annual ]
  a microvascular complication determined by glomerular filtration rate < 70 mL/min/1.73m2
• peripheral diabetic neuropathy [ Time Frame: annual ]
  a microvascular complication defined as the presence of Michigan Neuropathy Screening Instrument (MNSI) exam score >2 and <8 out of 10 appropriate responses to the Semmes-Weinstein monofilament (SW-MF) in either foot.
• cardiac function [ Time Frame: year 2 ]
  a macrovascular (cardiovascular) risk indicator determined by echocardiogram
• arterial stiffness [ Time Frame: year 5 ]
  a macrovascular (cardiovascular) risk indicator determined by pulse wave velocity
• cardiovascular risk lipid values [ Time Frame: annual ]
  a macrovascular (cardiovascular) risk indicator determined by abnormal lipid value for LDL (>= 130 mg/dL) or triglycerides (>= 300 mg/dL)

Current Secondary Outcome Measures (submitted: March 29, 2016)

• glycemic control [ Time Frame: every 12 months ]
  determined by HbA1c (annual)
• psychological disorder [ Time Frame: every 12 months ]
  determined by scores on the following participant self-report standard surveys: (a) the Beck Depression Inventory II (BDI-II), (b) the Patient Health Questionnaire (PHQ) scales for somatic symptoms, anxiety, and alcohol use; participants are also interviewed about emotional or mental health problems involving referral, treatment, or hospitalization, and psychiatric diagnoses made by a non-study source that can be confirmed according to standard study criteria from acquired medical records are also recorded
• body composition [ Time Frame: every 12 months ]
  determined by body mass index (BMI) computed from physical measurements of height and weight
• insulin sensitivity and beta cell function [ Time Frame: participant years 6 and 9 from baseline ]
  determined by oral glucose tolerance test (at 6 and 9 years from randomization) to derive measures of insulin sensitivity (1/insulin0), insulin secretion (ΔC-peptide30-0/Δglucose30-0, Δinsulin30-0/Δglucose30-0 if not on insulin), and the oral disposition index (oDI = insulin sensitivity x insulin secretion)
• eating disorder [ Time Frame: every 12 months ]
  determined by score on participant self report questionnaire Eating Disorder Diagnostic Scale (EDDS)
• health-related quality of life [ Time Frame: every 12 months ]
  determined by score on the participant self report questionnaire Pediatric Quality of Life Inventory version 4.0 with age-specific versions for teen (13-18), young adult (19-25), and adult (≥26)
• blood pressure [ Time Frame: every 12 months ]
  determined by collection of blood pressure
• sleep function [ Time Frame: years 2-3 ]
  determined by scores on standard questionnaires and in-lab polysomnogram
• life stress [ Time Frame: every 12 months ]
  determined by participant self report questionnaire based on the Yeaworth Adolescent Life Change Event Scale
• healthcare usage [ Time Frame: every 6 months ]
  determined by participant self report about visits, referrals, treatments, tests, and procedures related to healthcare

Original Secondary Outcome Measures (submitted: December 4, 2014)

• glycemic control [ Time Frame: annual ]
  determined by HbA1c (annual)
• psychological disorder [ Time Frame: annual ]
  determined by scores on the following participant self-report standard surveys: (a) the Beck Depression Inventory II (BDI-II), (b) the Patient Health Questionnaire (PHQ) scales for somatic symptoms, anxiety, and alcohol use; participants are also interviewed about emotional or mental health problems involving referral, treatment, or hospitalization, and psychiatric diagnoses made by a non-study source that can be confirmed according to standard study criteria from acquired medical records are also recorded
• body composition [ Time Frame: annual ]
  determined by body mass index (BMI) computed from physical measurements of height and weight
• insulin sensitivity and beta cell function [ Time Frame: participant years 6 and 9 from baseline ]
  determined by oral glucose tolerance test (at 6 and 9 years from randomization) to derive measures of insulin sensitivity (1/insulin0), insulin secretion (ΔC-peptide30-0/Δglucose30-0, Δinsulin30-0/Δglucose30-0 if not on insulin), and the oral disposition index (oDI = insulin sensitivity x insulin secretion)
• eating disorder [ Time Frame: annual ]
  determined by score on participant self report questionnaire Eating Disorder Diagnostic Scale (EDDS)
• health-related quality of life [ Time Frame: annual ]
  determined by score on the participant self report questionnaire Pediatric Quality of Life Inventory version 4.0 with age-specific versions for teen (13-18), young adult (19-25), and adult (≥26)
• blood pressure [ Time Frame: annual ]
  determined by collection of blood pressure
• sleep function [ Time Frame: years 2-3 ]
  determined by scores on standard questionnaires and in-lab polysomnogram
• life stress [ Time Frame: annual ]
  determined by participant self report questionnaire based on the Yeaworth Adolescent Life Change Event Scale
• healthcare usage [ Time Frame: every 6 months ]
  determined by participant self report about visits, referrals, treatments, tests, and procedures related to healthcare

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: TODAY2 Phase 2 Follow-up
• Official Title: Long-term Post-Intervention Follow-up of the TODAY Cohort (Treatment Options for Type 2 Diabetes in Youth and Adolescents)

Brief Summary

The primary objective of T2P2 is to track the progression of T2D and related comorbidities and complications in the TODAY cohort as they transition to young adulthood. We hypothesize that:

• Youth-onset type 2 diabetes (T2D) will progress rapidly and result in high rates of diabetes-related medical complications and comorbidities.
• The rapid rate of progression is related to increased insulin resistance characteristic of puberty, worse β-cell function, degree of glycemic control, control of non-glycemic factors, and obesity itself.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Blood and urine are collected annually and shipped to the study's Central Biospecimen Laboratory for analysis and storage.

• Sampling Method: Non-Probability Sample
• Study Population: All subjects randomized into the TODAY study are eligible to participate in T2P2. There are no additional inclusion or exclusions criteria for participation in T2P2.
• Condition: Type 2 Diabetes

Intervention

Other: TODAY cohort

This protocol is observation only and involves no intervention, care, treatment, or management.

Study Groups/Cohorts

TODAY cohort

All subjects randomized to the TODAY clinical trial are eligible to participate in T2P2. The study performs long-term observation only and administers no treatment, care, or management.

Intervention: Other: TODAY cohort

Publications *

• TODAY Study Group. Health Care Coverage and Glycemic Control in Young Adults With Youth-Onset Type 2 Diabetes: Results From the TODAY2 Study. Diabetes Care. 2020 Oct;43(10):2469-2477. doi: 10.2337/dc20-0760. Epub 2020 Aug 10.
• TODAY Study Group. Longitudinal Changes in Cardiac Structure and Function From Adolescence to Young Adulthood in Participants With Type 2 Diabetes Mellitus: The TODAY Follow-Up Study. Circ Heart Fail. 2020 Jun;13(6):e006685. doi: 10.1161/CIRCHEARTFAILURE.119.006685. Epub 2020 Jun 5.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 7, 2019): 517
• Original Estimated Enrollment (submitted: December 4, 2014): 506
• Actual Study Completion Date: January 17, 2020
• Actual Primary Completion Date: January 17, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participated in TODAY clinical trial.

Exclusion Criteria:

-

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02310724
• Other Study ID Numbers: DK61230-T2P2; U01DK061230 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

The TODAY/TODAY2 Study Group engages in a number of methods to disseminate and share resources.

• Findings are reported in manuscripts and presentations.
• An active Ancillary Studies Committee reviews proposals to access the study cohort, the central database, and stored biospecimens.
• Materials from the TODAY lifestyle intervention program and the standard diabetes education manual for adolescents developed by study experts are made available for public access on the website https://today.bsc.gwu.edu/web/today/home.
• The study group adheres to the policies of the NIDDK Central Repositories to make data available to other scientific investigators. A TODAY2 de-identified database will be prepared and transferred along with excess stored biospecimens. Appropriate informed consent is required to transfer stored biospecimens.
• TODAY establishes collaborative arrangements to work with other federally funded study groups.

• Supporting Materials: Study Protocol
• Time Frame: Data will be prepared and provided to the NIDDK Data Repository in early 2022
• Access Criteria: Currently with approval of the Ancillary Studies Committee and after 2022 as determined by the NIDDK Data Repository

• Current Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Original Study Sponsor: Same as current

Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• National Eye Institute (NEI)

Investigators

• Study Chair: Philip S Zeitler, MD PhD; University of Colorado Denver Children's Hospital
• Principal Investigator: Silva Arslanian, MD; University of Pittsburgh
• Principal Investigator: Sonia Caprio, MD; Yale University
• Principal Investigator: Jeanie B Tryggestad, MD; University of Oklahoma Health Science Center
• Principal Investigator: Mitchell E Geffner, MD; Children's Hospital Los Angeles
• Principal Investigator: Robin S Goland, MD; Columbia University Naomi Berrie Diabetes Center
• Principal Investigator: Lorraine L Katz, MD; Children's Hospital of Philadelphia
• Principal Investigator: Lori MB Laffel, MD; Joslin Diabetes Center
• Principal Investigator: Jane L Lynch, MD; University of Texas Health Sciences Center at San Antonio
• Principal Investigator: Siripoom V McKay, MD; Baylor College of Medicine
• Principal Investigator: Rose Gubitosi-Klug, MD; Case Western Reserve University Rainbow Babies and Children's Hospital
• Principal Investigator: David M Nathan, MD; Massachusetts General Hospital
• Principal Investigator: Sherida E Tollefsen, MD; St. Louis University
• Principal Investigator: Ruth S Weinstock, MD PhD; SUNY Upstate Medical Center
• Principal Investigator: Neil H White, MD; Washington University School of Medicine

• PRS Account: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Verification Date: July 2021