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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kathryn Hirst, George Washington University
ClinicalTrials.gov Identifier:
NCT00081328
First received: April 8, 2004
Last updated: December 8, 2014
Last verified: December 2014
  Purpose

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).

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.


Condition Intervention Phase
Diabetes Mellitus, Type II
Drug: Metformin
Drug: Rosiglitazone
Behavioral: Lifestyle Program
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Treatment Failure (Loss of Glycemic Control) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Insulin Sensitivity [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Safety [ Time Frame: Reported as occurred during study follow-up. ] [ Designated as safety issue: Yes ]
    Number of serious adverse events reported during the trial. Participant could have multiple episodes reported.

  • Insulin Secretion [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Body Composition -- BMI [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Body Composition -- Waist Circumference [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Body Composition -- Bone Density [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Body Composition -- Fat Mass [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Comorbidity -- Hypertension [ Time Frame: Data collected at baseline and during follow-up. ] [ Designated as safety issue: No ]
    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.

  • Comorbidity -- LDL Dyslipidemia [ Time Frame: Data collected at baseline and during follow-up. ] [ Designated as safety issue: No ]
    A diagnosis was made from out-of-range value >= 130 mg/dL sustained over 6 months or put on lipid lowering medication.

  • Comorbidity -- Triglycerides Dyslipidemia [ Time Frame: Data collected at baseline and during follow-up. ] [ Designated as safety issue: No ]
    A diagnosis was made by an out-of-range value >=150 mg/dL sustained over 6 months or on appropriate lipid lowering medication.


Enrollment: 699
Study Start Date: May 2004
Study Completion Date: February 2014
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Metformin alone
Drug: Metformin
capsule, 1000 mg bid
Experimental: 2
Metformin + Rosiglitazone
Drug: Metformin
capsule, 1000 mg bid
Drug: Rosiglitazone
capsule, 4 mg bid
Experimental: 3
Metformin + Lifestyle Program
Drug: Metformin
capsule, 1000 mg bid
Behavioral: Lifestyle Program
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (during Screening and Run-in period):

  • 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.
  • 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.

Exclusion Criteria (during Screening and Run-in period):

  • 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.
  • 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.

Inclusion Criteria (post Run-in and Randomization):

  • 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.

Exclusion Criteria (post Run-in and Randomization):

  • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00081328

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
University of Colorado Health Sciences Center, The Children's Hospital
Denver, Colorado, United States, 80262
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
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 Health Sciences Center
St Louis, Missouri, United States, 63104
Washington University Department of Pediatrics
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, 13210
United States, Ohio
Case Western Reserve
Cleveland, Ohio, United States, 44106
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 93104
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
Sponsors and Collaborators
Investigators
Principal Investigator: Phil Zeitler, MD, PhD University of Colorado, Denver
Principal Investigator: Kathryn Hirst, PhD George Washington University
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Kathryn Hirst, Principal Investigator of Coordinating Center, George Washington University
ClinicalTrials.gov Identifier: NCT00081328     History of Changes
Other Study ID Numbers: IND - DK61230-TODAY
Study First Received: April 8, 2004
Results First Received: September 26, 2014
Last Updated: December 8, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Rosiglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 30, 2015