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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Kathryn Hirst, George Washington University
ClinicalTrials.gov Identifier:
NCT01364350
First received: May 24, 2011
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
Diabetes Mellitus Type 2 in Obese
Other: standard of care in general clinical practice

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: TODAY2 Phase 1 Immediate Post-Intervention Observational Follow-up Study of the TODAY Clinical Trial Cohort

Resource links provided by NLM:


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

Primary Outcome Measures:
  • effects of TODAY treatment assignment on long-term glycemic control [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • glycemic control [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: Yes ]
    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.

  • safety [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: Yes ]
    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.

  • insulin sensitivity and secretion [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: No ]

    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.


  • cardiovascular risk factors [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: No ]
    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.

  • microvascular complications [ Time Frame: observed for 2 years in phase 1 ] [ Designated as safety issue: Yes ]

    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.



Biospecimen Retention:   Samples Without DNA

Blood and urine are collected on an annual basis and sent to the Central Biospecimen Laboratory for analysis and storage.

Analyses performed on an annual basis are: HbA1c, insulin sensitivity and secreation (fasting glucose, insulin, C-peptide, and proinsulin), 2-hour OGTT, pancreatic autoimmunity, serum creatinine, liver function tests, lipids (LDL, triglycerides, free fatty acids, lipoprotein subclass levels, average LDL particle density, and total apoB levels), cardiovascular risk factors (fibrinogen, c-reactive protein, homocysteine vitamin B-12, plasminogran activator inhibitor-1, interleukin-6), microalbumin.

HbA1c is also analyzed quarterly.


Enrollment: 550
Study Start Date: March 2011
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   12 Years to 24 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

participants in the TODAY clinical trial

Criteria

Inclusion Criteria:

  • Participated in the TODAY clinical trial.
  • Provided informed consent to participate in T2P1.
  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: NCT01364350

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
University of Colorado Denver
Denver, Colorado, United States, 80262
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06519
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
St Louis, Missouri, United States, 63104
Washington University
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, 13214
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73117
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: Silva Arslanian, MD Children's Hospital of Pittsburgh
Principal Investigator: Sonia Caprio, MD Yale University
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 Early Recognition Center
Study Chair: Phil Zeitler, MD PhD University of Colorado, Denver
Principal Investigator: Kathryn Hirst, PhD George Washington University
  More Information

No publications provided

Responsible Party: Kathryn Hirst, Principal Investigator of Coordinating Center, George Washington University
ClinicalTrials.gov Identifier: NCT01364350     History of Changes
Other Study ID Numbers: DK61230-T2P1
Study First Received: May 24, 2011
Last Updated: July 1, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
type 2 diabetes mellitus
pediatrics
post-intervention study
metformin
complications

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 16, 2014