Diabetes Mellitus, Type IIPhase 3TODAYNCT00081328

Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)

A Phase 3 study testing Metformin, Rosiglitazone and Lifestyle Program in people with Diabetes Mellitus, Type II, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 16 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) has sponsored a consortium of investigators to conduct a clinical treatment trial, Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY). Read more about this study

Who is it for?: Ages 10 to 17 years
Conditions the study is for: Diabetes Mellitus, Type II
What is being tested?: Metformin, Rosiglitazone and Lifestyle Program
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 699 participants
Where: 16 sitesUnited States
Study dates: May 2004to Feb 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 10 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Diabetes by ADA criteria (laboratory determinations of fasting glucose ≥ 126 mg/dL, random glucose ≥ 200 mg/dL, or two-hour OGTT glucose ≥ 200 mg/dL) documented and confirmed in medical record. For patients diagnosed with diabetes during screening who have a normal fasting glucose but an elevated two-hour glucose during an OGTT, the HbA1c must be ≥ 6%.
Duration since diagnosis less than two years by date of randomization.
BMI ≥ 85th percentile documented at time of diagnosis or at screening.
Fasting C-peptide at screening (drawn at least one week after treatment for ketosis or acidosis, if applicable) > 0.6 ng/mL.
Absence of pancreatic autoimmunity (both GAD and ICA512 negative).
Age 10-17, with randomization prior to 18th birthday.

Show all 17Show fewer

Signed informed consent/assent forms for the pre-randomization period.
A family member or adult closely involved in the daily activities of the child agrees to participate in the child's treatment.
Fluency in English or Spanish for both child and family member.
Patient and family able to fully participate in trial protocol in the opinion of the investigator.
Duration since diagnosis less than 2 years at randomization.
HbA1c < 8% on metformin alone.
Age 10-17, with randomization before patient is 18 years old.
Signed consent/assent forms for randomization and the post-randomization phase.
A family member or adult closely involved in the daily activities of the child agrees to participate in the child's treatment.
Fluency in English or Spanish for both child and family member.
Patient and family able to fully participate in trial protocol in the opinion of the investigator.

Who cannot join

Participating in another interventional research study protocol in the past 30 days.
Genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
Patient on inhaled steroids at dose above 1000 mcg daily Flovent equivalent.
Patient on a course of oral steroids within the last 60 days or on oral steroids more than 20 days during the past year.
Patient on medication(s) that are known to affect insulin sensitivity or secretion within the last 30 days.
Patient on medication(s) that are known to cause weight gain within the last 30 days.

Show all 41Show fewer

Patient on any weight-loss medication(s) within the last 30 days.
Patient on medication(s) known to affect the metabolism of study drug.
Inability to comprehend the lowest grade level at which lifestyle intervention materials are prepared, for both child and participating family member.
Females who are pregnant, planning to become pregnant within two years of enrollment, or who admit sexual activity without appropriate contraception.
Calculated creatinine clearance < 70 mL/min.
Any transaminase > 2.5 ULN. If any transaminase 1.5-2.5 times ULN, then patient must be appropriately evaluated by PCP (minimum evaluation includes ceruloplasmin level, alpha-1 antitrypsin phenotype, ANA, anti-smooth muscle antibody, anti-LKM antibody, anti-HCV, and anti-HBc total antibody not IgM, iron, and TIBC) and is eligible if all other causes for elevation are ruled out and it is presumed due only to non-alcoholic fatty liver disease (NAFLD).
Diabetic ketoacidosis (DKA) at any time after diagnosis unless only a single episode of DKA related to a significant medical illness.
Physical limitations preventing patient from being randomized to the lifestyle intervention.
Patient plans to leave the geographic area within one calendar year.
Abnormal reticulocyte count or HbA1c chromatogram at time of screening.
Admitted use of anabolic steroids within the past 60 days.
Other significant organ system illness or condition (including psychiatric or developmental disorder) that would prevent participation in the opinion of the investigator.
Patient participates in a formal weight-loss program.
Refractory hypertension: average systolic blood pressure ≥ 150 mmHg or average diastolic blood pressure ≥ 95 mmHg despite appropriate medical therapy.
Refractory hyperlipidemia: total cholesterol > 300 mg/dL or LDL > 190 mg/dL or triglycerides > 800 mg/dL, despite appropriate medical therapy.
Refractory anemia: hematocrit < 30% or hemoglobin < 10 gm/dL despite appropriate medical therapy.
Patient on a thiazolidinedione (TZD) within the last 12 weeks.
Patient on non-study diabetes medications within the past 6 weeks.
Patient on inhaled steroids at dose above 1000 mcg daily Flovent equivalent.
Patient on a course of oral steroids within the last 60 days or on oral steroids more than 20 days during the past year.
Patient on medication(s) that are known to affect insulin sensitivity or secretion within the last 30 days.
Patient on medication(s) that are known to cause weight gain within the last 30 days.
Patient on any weight-loss medication(s) within the last 30 days.
Patient on medication(s) known to affect the metabolism of study drug.
Inability to comprehend the lowest grade level at which lifestyle intervention materials are prepared, for both child and participating family member, assessed by mastery of standard diabetes education program administered during run-in.
Inability to comply with requirements of study during run-in period.
Females who are pregnant, planning to become pregnant within two years of enrollment, or who admit sexual activity without appropriate contraception.
Calculated creatinine clearance < 70 mL/min.
Physical limitations preventing patient from being randomized to the lifestyle intervention.
Patient plans to leave the geographic area within one calendar year.
Admitted use of anabolic steroids within 60 days.
Other significant organ system illness or condition (including psychiatric or developmental disorder) that would prevent participation in the opinion of the investigator.
Patient participates in a formal weight loss program.
Episode of DKA during the run-in.30.
Edema at the time of randomization (a participant who experiences edema during run-in must have recovered within 2 weeks and be edema free for 1 week prior to randomization).

Trial locations and contacts

16 sites in 1 country.

City, postcode or hospital

16 sites in 1 country

United States16 sites

Massachusetts General Hospital Diabetes Center
Boston, Massachusetts, 02114
Joslin Diabetes Center
Boston, Massachusetts, 02215
Case Western Reserve
Cleveland, Ohio, 44106
University of Colorado Health Sciences Center, The Children's Hospital
Denver, Colorado, 80262
Baylor College of Medicine
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
Yale University
New Haven, Connecticut, 06520
Columbia University Medical Center
New York, New York, 10032
University of Oklahoma
Oklahoma City, Oklahoma, 93104
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
George Washington University Biostatistics Center
Rockville, Maryland, 20852
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Saint Louis University Health Sciences Center
St Louis, Missouri, 63104
Washington University Department of Pediatrics
St Louis, Missouri, 63110
State University of New York Upstate Medical University
Syracuse, New York, 13210

Other trials in United States

About this study

Official title: Studies to Treat Or Prevent Pediatric Type 2 Diabetes (STOPP-T2D) Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Clinical Trial

The primary objective of the TODAY trial is to compare the efficacy of three treatment arms on time to treatment failure based on glycemic control. The secondary aims are to:

compare and evaluate the safety of the three treatment arms;
compare the effects of the three treatments on the pathophysiology of type 2 diabetes (T2D) with regards to beta cell function and insulin resistance, body composition, nutrition, physical activity and aerobic fitness, cardiovascular risk factors, microvascular complications, quality of life, and psychological outcomes;
evaluate the influence of individual and family behaviors on treatment response; and
compare the relative cost effectiveness of the three treatment arms.

The three treatment regimens are: (1) metformin alone, (2) metformin plus rosiglitazone, and (3) metformin plus an intensive lifestyle intervention called the TODAY Lifestyle Program (TLP). The study recruits patients over a three-year period and follows patients for a minimum of two years. Patients are randomized within two years of the diagnosis of T2D.

Read the detailed description

T2DM has dramatically increased throughout the world in many ethnic groups and among people with diverse social and economic backgrounds. Over the last decade, the increase in the number of children and youth with T2DM has been labeled an "epidemic". Before the 1990s, it was rare for most pediatric centers to have patients with T2DM. By 1994, T2DM patients represented up to 16% of new cases of diabetes in children in urban areas, and by 1999, depending on geographic location, the range of percent of new cases due to T2DM was between 8-45% and disproportionately represented in minority populations.

T2DM in children and youth, as in adults, is due to the combination of insulin resistance and relative β-cell failure. It appears that there are a host of genetic and environmental risk factors for insulin resistance and limited β-cell reserve. The epidemic of pediatric T2DM is coincident with the rise in the number of children who are overweight or at risk for overweight and with a decrease in the physical activity pattern of youth. There has been a strong association between T2DM and the onset of puberty, a positive family history of T2DM, and elements of the metabolic syndrome such as acanthosis nigricans and polycystic ovarian syndrome (PCOS).

Preceding the development of frank diabetes, children and youth experience a period of prediabetes. Prediabetes is defined as either elevated fasting glucose or impaired glucose tolerance. Despite the dramatic increase in the number of cases of prediabetes and T2DM in pediatric populations, there have been no published large-scale studies investigating the pathophysiology, treatment, and complications of these disorders in children and youth. The long-term complications and costs associated with T2DM make such studies imperative. Between 1997 and 2002, the estimated cost of diabetes with regard to direct medical cost increased from $44 billion to $92 billion, and the total cost increased from $98 billion to $132 billion. The vast majority of monies are spent on the long-term complications of this disorder. Since the long-term microvascular and cardiovascular complications relate to duration of diabetes and to control of glycemia, it could be hypothesized that the increasing number of children and youth diagnosed with T2DM, if not effectively treated, could dramatically add to the economic burden of this disease over the ensuing decades.

Except in American Indian youth, there are no population-based data available with regard to prevalence of T2DM. Instead, only clinic-based reports indicate that there has been a tremendous increase in the number of children and adolescents with T2DM. T2DM occurs almost exclusively in children and youth who are overweight or at risk for overweight (BMI > 85th percentile for age). At the time of diagnosis, most pediatric patients are in the midst of Tanner Stage 2-4 puberty. Puberty contributes to insulin resistance due to augmentation of growth hormone secretion, and if these normal pubertal physiologic changes are not compensated for by increased insulin secretion, frank diabetes will develop. Half to three-quarters of patients have a parent and close to ninety percent have at least one first or second degree relative with T2DM. The clinical presentation of T2DM in youth ranges from mild asymptomatic hyperglycemia to severe ketoacidosis. In those who present with clinical symptoms due to hyperglycemia, glycosuria and weight loss are present in 20-40%, ketonuria is present in 33% and ketoacidosis is found in 5-10%. Patients without clinical symptoms are diagnosed as the result of routine blood or urine testing during a health care visit or by investigating a variety of complaints such as chronic infection, sleep apnea, hyperlipidemia, hypertension, and hirsutism or irregular periods associated with PCOS. It may be difficult to distinguish T1DM from T2DM at presentation. The absence of autoantibodies is a prerequisite for the diagnosis of T2DM. In addition, evidence of residual insulin secretion is suggestive of T2DM rather than T1DM.

Patients with T2DM have dual abnormalities of insulin resistance and insulin deficiency. It is hypothesized that to achieve the level of glycemic control required to optimize long-term outcome and decrease or prevent microvascular complications, treatment regimens should theoretically be designed to improve insulin resistance and preserve residual β-cell function. The available anti-diabetic agents have not been adequately evaluated in pediatric patients. This is particularly relevant with regard to using combination therapy to improve glycemic control or lifestyle interventions aimed at obesity and sedentary behavior.

Conditions: Diabetes Mellitus, Type II
Being tested: Metformin, Rosiglitazone, Lifestyle Program
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MetforminDrug
capsule, 1000 mg bid
RosiglitazoneDrug
capsule, 4 mg bid
Lifestyle ProgramBehavioural
a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study

Study groups in NCT00081328
Study group	Role	What they receive
1	Experimental	Metformin alone Receives: Drug: Metformin
2	Experimental	Metformin + Rosiglitazone Receives: Drug: Metformin; Drug: Rosiglitazone
3	Experimental	Metformin + Lifestyle Program Receives: Drug: Metformin; Behavioral: Lifestyle Program

What is being measured

The primary outcome is the main question the study is designed to answer.

Treatment Failure (Loss of Glycemic Control)
Defined as A1c persistently >=8% over a 6-month period or persistent metabolic decompensation (inability to wean insulin within 3 months of initiation or the occurrence of a second episode within three months of discontinuing insulin)
Measured: Study duration - 2 years to 6.5 years of follow up from randomization

Secondary outcomes (10)

Insulin Sensitivity
All participants were followed to 24 months. Insulin sensitivity is measured from OGTT as inverse of fasting insulin (mL/uU). The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.
Measured: 24 months
Number of Serious Adverse Events
Number of serious adverse events reported during the trial. Participant could have multiple episodes reported.
Measured: Reported as occurred during study follow-up - 2 years to 6.5 years from randomization.
Insulin Secretion
Insulinogenic index determined from OGTT as difference in insulin at 30 minutes minus 0 minutes divided by difference in glucose at 30 minutes minus 0 minutes. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.
Measured: 24 months
Body Composition -- BMI
Body mass index (BMI) measured in kg per meters squared. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.
Measured: 24 months
Body Composition -- Waist Circumference
Waist circumference (cm) measured at the iliac crest at its outermost point with the measuring tape placed around the participant in a horizontal plane parallel to the floor at the mark and the measurement teken at the end of normal expiration without the tape compressing the skin. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.
Measured: 24 months
Body Composition -- Bone Density
Measured by DXA, both whole body scan and AP-spine scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan.
Measured: 24 months
Body Composition -- Fat Mass
Determined by DXA whole body scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan.
Measured: 24 months
Comorbidity -- Hypertension
A diagnosis was made by an out-of-range value >=95th percentile or systolic >=130 or diastolic >=80 sustained over 6 months or on an anti-hypertensive medication.
Measured: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.
Comorbidity -- LDL Dyslipidemia
A diagnosis was made from out-of-range value >= 130 mg/dL sustained over 6 months or put on lipid lowering medication.
Measured: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.
Comorbidity -- Triglycerides Dyslipidemia
A diagnosis was made by an out-of-range value >=150 mg/dL sustained over 6 months or on appropriate lipid lowering medication.
Measured: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2004Feb 2014

First posted12 Apr 2004 (estimated)
Study startMay 2004
Primary completionFeb 2011
Study completionFeb 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (79)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type IIStudies of the same condition, open and under way.
More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 699 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00081328
Sponsor's protocol ID: IND - DK61230-TODAY
Other IDs: U01DK061230
Acronym: TODAY
Status last verified: Jul 2021
First submitted: 8 Apr 2004
Last updated: 30 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: Data are available at the NIDDK Central Repository

Publications

TODAY Study Group; Zeitler P, Epstein L, Grey M, Hirst K, Kaufman F, Tamborlane W, Wilfley D. Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatr Diabetes. 2007 Apr;8(2):74-87. doi: 10.1111/j.1399-5448.2007.00237.x.
PubMed 17448130
Songer T, Glazner J, Coombs LP, Cuttler L, Daniel M, Estrada S, Klingensmith G, Kriska A, Laffel L, Zhang P; the TODAY Study Group. Examining the economic costs related to lifestyle and pharmacological interventions in youth with Type 2 diabetes. Expert Rev Pharmacoecon Outcomes Res. 2006 Jun 1;6(3):315-324. doi: 10.1586/14737167.6.3.315.
PubMed 19774104
Grey M, Schreiner B, Pyle L. Development of a diabetes education program for youth with type 2 diabetes. Diabetes Educ. 2009 Jan-Feb;35(1):108-16. doi: 10.1177/0145721708325156.
PubMed 19244566
TODAY Study Group. Design of a family-based lifestyle intervention for youth with type 2 diabetes: the TODAY study. Int J Obes (Lond). 2010 Feb;34(2):217-26. doi: 10.1038/ijo.2009.195. Epub 2009 Oct 13.
PubMed 19823189
Larkin ME, McGuigan P, Richards D, Blumenthal K, Milaszewski K, Higgins L, Schanuel J, Long C. Collaborative staffing model: reducing the challenges of study coordination in multi-site clinical trials. Applied Clinical Trials 2011, http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/Articles/Collaborative-Staffing-Model/ArticleStandard/Article/detail/703023 (accessed 01/15/2011).
Chadwick JQ, Copeland KC, Daniel MR, Erb-Alvarez JA, Felton BA, Khan SI, Saunkeah BR, Wharton DF, Payan ML. Partnering in research: a national research trial exemplifying effective collaboration with American Indian Nations and the Indian Health Service. Am J Epidemiol. 2014 Dec 15;180(12):1202-7. doi: 10.1093/aje/kwu246. Epub 2014 Nov 11.
PubMed 25389367
Chadwick JQ, Van Buren DJ, Morales E, Timpson A, Abrams EL, Syme A, Preske J, Mireles G, Anderson B, Grover N, Laffel L. Structure to utilize interventionists' implementation experiences of a family-based behavioral weight management program to enhance the dissemination of the standardized intervention: The TODAY study. Clin Trials. 2017 Aug;14(4):406-412. doi: 10.1177/1740774517707727. Epub 2017 May 9.
PubMed 28486851
Chadwick JQ, Copeland KC, Branam DE, Erb-Alvarez JA, Khan SI, Peercy MT, Rogers ME, Saunkeah BR, Tryggestad JB, Wharton DF. Genomic Research and American Indian Tribal Communities in Oklahoma: Learning From Past Research Misconduct and Building Future Trusting Partnerships. Am J Epidemiol. 2019 Jul 1;188(7):1206-1212. doi: 10.1093/aje/kwz062.
PubMed 31081852
Songer TJ, Haymond MW, Glazner JE, Klingensmith GJ, Laffel LM, Zhang P, Hirst K; TODAY Study Group. Healthcare and associated costs related to type 2 diabetes in youth and adolescence: the TODAY clinical trial experience. Pediatr Diabetes. 2019 Sep;20(6):702-711. doi: 10.1111/pedi.12869. Epub 2019 Jun 6.
PubMed 31119838
Klingensmith GJ, Pyle L, Arslanian S, Copeland KC, Cuttler L, Kaufman F, Laffel L, Marcovina S, Tollefsen SE, Weinstock RS, Linder B; TODAY Study Group. The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY study. Diabetes Care. 2010 Sep;33(9):1970-5. doi: 10.2337/dc10-0373. Epub 2010 Jun 2.
PubMed 20519658
Copeland KC, Zeitler P, Geffner M, Guandalini C, Higgins J, Hirst K, Kaufman FR, Linder B, Marcovina S, McGuigan P, Pyle L, Tamborlane W, Willi S; TODAY Study Group. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011 Jan;96(1):159-67. doi: 10.1210/jc.2010-1642. Epub 2010 Oct 20.
PubMed 20962021
TODAY Study Group; Wilfley D, Berkowitz R, Goebel-Fabbri A, Hirst K, Ievers-Landis C, Lipman TH, Marcus M, Ng D, Pham T, Saletsky R, Schanuel J, Van Buren D. Binge eating, mood, and quality of life in youth with type 2 diabetes: baseline data from the today study. Diabetes Care. 2011 Apr;34(4):858-60. doi: 10.2337/dc10-1704. Epub 2011 Feb 28.
PubMed 21357794
Anderson BJ, Edelstein S, Abramson NW, Katz LE, Yasuda PM, Lavietes SJ, Trief PM, Tollefsen SE, McKay SV, Kringas P, Casey TL, Marcus MD. Depressive symptoms and quality of life in adolescents with type 2 diabetes: baseline data from the TODAY study. Diabetes Care. 2011 Oct;34(10):2205-7. doi: 10.2337/dc11-0431. Epub 2011 Aug 11.
PubMed 21836107
Laffel L, Chang N, Grey M, Hale D, Higgins L, Hirst K, Izquierdo R, Larkin M, Macha C, Pham T, Wauters A, Weinstock RS; TODAY Study Group. Metformin monotherapy in youth with recent onset type 2 diabetes: experience from the prerandomization run-in phase of the TODAY study. Pediatr Diabetes. 2012 Aug;13(5):369-75. doi: 10.1111/j.1399-5448.2011.00846.x. Epub 2012 Feb 27.
PubMed 22369102
Bacha F, Pyle L, Nadeau K, Cuttler L, Goland R, Haymond M, Levitsky L, Lynch J, Weinstock RS, White NH, Caprio S, Arslanian S; TODAY Study Group. Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY study. Pediatr Diabetes. 2012 Aug;13(5):376-83. doi: 10.1111/j.1399-5448.2011.00841.x. Epub 2012 Feb 15.
PubMed 22332798

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Studies to Treat Or Prevent Pediatric Type 2 Diabetes (STOPP-T2D) Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Clinical Trial
ClinicalTrials.gov ID: NCT00081328
Acronym / sponsor ID: TODAY / IND - DK61230-TODAY
Conditions: Diabetes Mellitus, Type II
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 699 participants (actual)
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
Study start: May 2004
Primary completion: Feb 2011 (actual)
Study completion: Feb 2014 (actual)
First posted: 12 Apr 2004 (estimated)
Results: Posted 16 Dec 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary objective of the TODAY trial is to compare the efficacy of three treatment arms on time to treatment failure based on glycemic control. The secondary aims are to:

compare and evaluate the safety of the three treatment arms;
compare the effects of the three treatments on the pathophysiology of type 2 diabetes (T2D) with regards to beta cell function and insulin resistance, body composition, nutrition, physical activity and aerobic fitness, cardiovascular risk factors, microvascular complications, quality of life, and psychological outcomes;
evaluate the influence of individual and family behaviors on treatment response; and
compare the relative cost effectiveness of the three treatment arms.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
1	Experimental	Drug: MetforminMetformin alone
2	Experimental	Drug: Metformin, Drug: RosiglitazoneMetformin + Rosiglitazone
3	Experimental	Drug: Metformin, Behavioral: Lifestyle ProgramMetformin + Lifestyle Program

Who may qualify

Ages: 10 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (17 listed)

Diabetes by ADA criteria (laboratory determinations of fasting glucose ≥ 126 mg/dL, random glucose ≥ 200 mg/dL, or two-hour OGTT glucose ≥ 200 mg/dL) documented and confirmed in medical record. For patients diagnosed with diabetes during screening who have a normal fasting glucose but an elevated two-hour glucose during an OGTT, the HbA1c must be ≥ 6%.
Duration since diagnosis less than two years by date of randomization.
BMI ≥ 85th percentile documented at time of diagnosis or at screening.
Fasting C-peptide at screening (drawn at least one week after treatment for ketosis or acidosis, if applicable) > 0.6 ng/mL.
Absence of pancreatic autoimmunity (both GAD and ICA512 negative).

Key exclusion criteria (41 listed)

Participating in another interventional research study protocol in the past 30 days.
Genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
Patient on inhaled steroids at dose above 1000 mcg daily Flovent equivalent.
Patient on a course of oral steroids within the last 60 days or on oral steroids more than 20 days during the past year.
Patient on medication(s) that are known to affect insulin sensitivity or secretion within the last 30 days.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Metformincapsule, 1000 mg bid	Drug	1, 2, 3
Rosiglitazonecapsule, 4 mg bid	Drug	2
Lifestyle Programa lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study	Behavioural	3

Primary outcome

Treatment Failure (Loss of Glycemic Control)
Time frame: Study duration - 2 years to 6.5 years of follow up from randomization
Defined as A1c persistently >=8% over a 6-month period or persistent metabolic decompensation (inability to wean insulin within 3 months of initiation or the occurrence of a second episode within three months of discontinuing insulin)

10 secondary outcomes

Insulin Sensitivity
Time frame: 24 months
Number of Serious Adverse Events
Time frame: Reported as occurred during study follow-up - 2 years to 6.5 years from randomization.
Insulin Secretion
Time frame: 24 months
Body Composition -- BMI
Time frame: 24 months
Body Composition -- Waist Circumference
Time frame: 24 months
Body Composition -- Bone Density
Time frame: 24 months
Body Composition -- Fat Mass
Time frame: 24 months
Comorbidity -- Hypertension
Time frame: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.
Comorbidity -- LDL Dyslipidemia
Time frame: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.
Comorbidity -- Triglycerides Dyslipidemia
Time frame: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Results and safety

Results posted to the registry on 16 Dec 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
1 Metformin Alone	232	232
2 Metformin + Rosliglitazone	233	233
3 Metformin + Lifestyle Program	234	234

Primary outcome: Treatment Failure (Loss of Glycemic Control)

Time frame: Study duration - 2 years to 6.5 years of follow up from randomization. Number. Unit: participants

Measure	1 Metformin Alone n = 232	2 Metformin + Rosliglitazone n = 233	3 Metformin + Lifestyle Program n = 234
Treatment failure	120	90	109
Did not fail treatment during trial	112	143	125

Population analysed: The entire cohort of 699 participants was included in the analysis.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
1 Metformin Alone	42 of 232 (18.1%)	215 of 232 (92.7%)	Not reported
2 Metformin + Rosliglitazone	34 of 233 (14.6%)	196 of 233 (84.1%)	Not reported
3 Metformin + Lifestyle Program	58 of 234 (24.8%)	213 of 234 (91%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 17448130TODAY Study Group; Zeitler P, Epstein L, Grey M, Hirst K, Kaufman F, Tamborlane W, Wilfley D. Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatr Diabetes. 2007 Apr;8(2):74-87. doi: 10.1111/j.1399-5448.2007.00237.x.
Background: PubMed 19774104Songer T, Glazner J, Coombs LP, Cuttler L, Daniel M, Estrada S, Klingensmith G, Kriska A, Laffel L, Zhang P; the TODAY Study Group. Examining the economic costs related to lifestyle and pharmacological interventions in youth with Type 2 diabetes. Expert Rev Pharmacoecon Outcomes Res. 2006 Jun 1;6(3):315-324. doi: 10.1586/14737167.6.3.315.
Background: PubMed 19244566Grey M, Schreiner B, Pyle L. Development of a diabetes education program for youth with type 2 diabetes. Diabetes Educ. 2009 Jan-Feb;35(1):108-16. doi: 10.1177/0145721708325156.
Background: PubMed 19823189TODAY Study Group. Design of a family-based lifestyle intervention for youth with type 2 diabetes: the TODAY study. Int J Obes (Lond). 2010 Feb;34(2):217-26. doi: 10.1038/ijo.2009.195. Epub 2009 Oct 13.
BackgroundLarkin ME, McGuigan P, Richards D, Blumenthal K, Milaszewski K, Higgins L, Schanuel J, Long C. Collaborative staffing model: reducing the challenges of study coordination in multi-site clinical trials. Applied Clinical Trials 2011, http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/Articles/Collaborative-Staffing-Model/ArticleStandard/Article/detail/703023 (accessed 01/15/2011).
Background: PubMed 25389367Chadwick JQ, Copeland KC, Daniel MR, Erb-Alvarez JA, Felton BA, Khan SI, Saunkeah BR, Wharton DF, Payan ML. Partnering in research: a national research trial exemplifying effective collaboration with American Indian Nations and the Indian Health Service. Am J Epidemiol. 2014 Dec 15;180(12):1202-7. doi: 10.1093/aje/kwu246. Epub 2014 Nov 11.
Background: PubMed 28486851Chadwick JQ, Van Buren DJ, Morales E, Timpson A, Abrams EL, Syme A, Preske J, Mireles G, Anderson B, Grover N, Laffel L. Structure to utilize interventionists' implementation experiences of a family-based behavioral weight management program to enhance the dissemination of the standardized intervention: The TODAY study. Clin Trials. 2017 Aug;14(4):406-412. doi: 10.1177/1740774517707727. Epub 2017 May 9.
Background: PubMed 31081852Chadwick JQ, Copeland KC, Branam DE, Erb-Alvarez JA, Khan SI, Peercy MT, Rogers ME, Saunkeah BR, Tryggestad JB, Wharton DF. Genomic Research and American Indian Tribal Communities in Oklahoma: Learning From Past Research Misconduct and Building Future Trusting Partnerships. Am J Epidemiol. 2019 Jul 1;188(7):1206-1212. doi: 10.1093/aje/kwz062.
Background: PubMed 31119838Songer TJ, Haymond MW, Glazner JE, Klingensmith GJ, Laffel LM, Zhang P, Hirst K; TODAY Study Group. Healthcare and associated costs related to type 2 diabetes in youth and adolescence: the TODAY clinical trial experience. Pediatr Diabetes. 2019 Sep;20(6):702-711. doi: 10.1111/pedi.12869. Epub 2019 Jun 6.
Results publication: PubMed 20519658Klingensmith GJ, Pyle L, Arslanian S, Copeland KC, Cuttler L, Kaufman F, Laffel L, Marcovina S, Tollefsen SE, Weinstock RS, Linder B; TODAY Study Group. The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY study. Diabetes Care. 2010 Sep;33(9):1970-5. doi: 10.2337/dc10-0373. Epub 2010 Jun 2.
Results publication: PubMed 20962021Copeland KC, Zeitler P, Geffner M, Guandalini C, Higgins J, Hirst K, Kaufman FR, Linder B, Marcovina S, McGuigan P, Pyle L, Tamborlane W, Willi S; TODAY Study Group. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011 Jan;96(1):159-67. doi: 10.1210/jc.2010-1642. Epub 2010 Oct 20.
Results publication: PubMed 21357794TODAY Study Group; Wilfley D, Berkowitz R, Goebel-Fabbri A, Hirst K, Ievers-Landis C, Lipman TH, Marcus M, Ng D, Pham T, Saletsky R, Schanuel J, Van Buren D. Binge eating, mood, and quality of life in youth with type 2 diabetes: baseline data from the today study. Diabetes Care. 2011 Apr;34(4):858-60. doi: 10.2337/dc10-1704. Epub 2011 Feb 28.
public access to intervention materials used in TODAYLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Data are available at the NIDDK Central Repository

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Phil Zeitler, MD, PhD principal investigator

University of Colorado, Denver

Kathryn Hirst, PhD principal investigator

George Washington University

16 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Failure (Loss of Glycemic Control) (time frame: Study duration - 2 years to 6.5 years of follow up from randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00081328, which also lists 79 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.