A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes (GRADE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by GRADE Study Group
Sponsor:
Collaborators:
Becton, Dickinson and Company
Bristol-Myers Squibb
Merck Sharp & Dohme Corp.
Novo Nordisk A/S
Hoffmann-La Roche
Sanofi
Information provided by (Responsible Party):
GRADE Study Group
ClinicalTrials.gov Identifier:
NCT01794143
First received: February 13, 2013
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

The GRADE Study is a pragmatic, unmasked clinical trial that will compare commonly used diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and patient-centered outcomes.


Condition Intervention Phase
Type 2 Diabetes
Comparative Effectiveness of Glycemia-lowering Medications
Drug: Sulfonylurea (glimepiride)
Drug: DPP-4 inhibitor (sitagliptin)
Drug: GLP-1 receptor agonist (liraglutide)
Drug: Insulin (glargine)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study

Resource links provided by NLM:


Further study details as provided by GRADE Study Group:

Primary Outcome Measures:
  • Time to HbA1c>=7%, while receiving metformin and the randomly assigned study medication [ Time Frame: Quarterly for 4 to 7 years ] [ Designated as safety issue: No ]
    The primary metabolic outcome is the time to primary failure defined as an HbA1c>=7% (53mmol/mol), subsequently confirmed.


Secondary Outcome Measures:
  • Time to HbA1c>7.5%, while receiving metformin and the randomly assigned study medication. [ Time Frame: Quarterly for 4 to 7 years ] [ Designated as safety issue: No ]
    The secondary metabolic outcome is time to HbA1c>7.5% (58 mmol/mol), confirmed.


Other Outcome Measures:
  • Time to HbA1c>7.5%, while receiving study medications and basal insulin [ Time Frame: Quarterly for 4 to 7 years ] [ Designated as safety issue: No ]
    The tertially metabolic outcome is the time to a HbA1c>7.5% (58 mmol/mol), confirmed, while receiving metformin, the originally assigned medication and basal insulin.


Estimated Enrollment: 5000
Study Start Date: May 2013
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sulfonylurea (glimepiride)
Sulfonylurea
Drug: Sulfonylurea (glimepiride)
Used in accordance with labeling and/or usual practice.
Other Name: Glimepiride
Active Comparator: DPP-4 inhibitor
DPP-4 inhibitor (sitagliptin)
Drug: DPP-4 inhibitor (sitagliptin)
Used in accordance with labeling and/or usual practice
Other Name: Sitagliptin
Active Comparator: GLP-1 receptor agonist
GLP-1 receptor agonist (liraglutide)
Drug: GLP-1 receptor agonist (liraglutide)
Used in accordance with labeling and/or usual practice.
Other Name: Liraglutide
Active Comparator: Insulin (glargine)
Insulin (glargine), Lantus
Drug: Insulin (glargine)
Used in accordance with labeling and/or usual practice.
Other Name: Lantus

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men or women diagnosed with diabetes at age ≥ 30 years (≥ 20 for American Indians)
  2. Duration of diagnosed diabetes < 10 years
  3. HbA1c criteria (at final run-in visit, ~2 weeks prior to randomization): 6.8-8.5%
  4. Taking a daily dose of ≥ 1000 mg metformin for a minimum of 8 weeks at final run-in
  5. Willingness to administer daily subcutaneous injections, take a second diabetes drug after randomization, potentially initiate insulin and intensify insulin therapy if study metabolic goals are not met, perform self-monitoring of blood glucose
  6. Fluent in either English or Spanish
  7. A negative pregnancy test for all females of childbearing potential (i.e. pre-menopausal, and not surgically sterile)
  8. Provision of signed and dated informed consent prior to any study procedures

Exclusion Criteria:

  1. Suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin) or "secondary" diabetes due to specific causes (e.g. previously diagnosed monogenic syndromes, pancreatic surgery, pancreatitis)
  2. Current or previous (within past 6 months) treatment with any diabetes drug/glucose-lowering medication other than metformin
  3. More than 10 years of treatment with metformin at time of randomization screening
  4. History of intolerance or allergy or other contraindications to any of the proposed study medications
  5. Resides in the same household with another GRADE study participant
  6. Current need for any specific glucose-lowering medications solely for other conditions, for example for polycystic ovary syndrome
  7. Symptomatic hyperglycemia requiring immediate therapy during screening or run-in, in the judgment of the physician
  8. A life-threatening event within 30 days prior to screening or currently planned major surgery
  9. Any major cardiovascular event in previous year, including history of myocardial infarction, stroke, or vascular procedure such as coronary artery or peripheral bypass grafting, stent placements (peripheral or coronary) or angioplasty.
  10. Plans for pregnancy during the course of the study for women of child-bearing potential
  11. History of or planning bariatric surgery, including banding procedures or surgical gastric and/or intestinal bypass (if banding removed, may be considered eligible after 1 year)
  12. History of congestive heart failure (NYHA 3 or greater)
  13. History of pancreatitis
  14. History of cancer, other than non-melanoma skin cancer, that required therapy in the 5 years prior to randomization
  15. Personal or family history of MEN-2 or family history of medullary thyroid cancer
  16. Serum creatinine >1.4 mg/dl in women and >1.5 mg/dl in men or end stage renal disease requiring renal replacement therapy
  17. History of severe liver disease or acute hepatitis or ALT > 3 times upper limit of normal
  18. Current alcoholism or excessive alcohol intake
  19. Previous organ transplant
  20. Treatment with oral or systemic glucocorticoids (other than short-term treatment, for example for poison ivy) or disease likely to require periodic or regular glucocorticoid therapy (inhaled steroids are allowed)
  21. Treatment with atypical antipsychotics
  22. History of hemolytic anemia, chronic transfusion requirement, or other condition rendering HbA1c results unreliable as indicator of chronic glucose levels, or hematocrit <35 for males and <33 for females
  23. Clinically or medically unstable with expected survival <1 year
  24. Unwillingness to permit sites to contact the PCP to communicate information about the study and the participant's data
  25. No non-study PCP or inability to identify such a PCP (who will provide non-study care) by the time of final run-in
  26. Participation in another interventional clinical trial
  27. Previous randomization in the GRADE study
  28. In the opinion of the principal investigator (PI), any other factor, including language barrier, likely to limit compliance with the protocol
  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: NCT01794143

Contacts
Contact: Heidi Krause-Steinrauf, MS heidi@bsc.gwu.edu
Contact: Paula McGee, MS Paulaf@bsc.gwu.edu

  Hide Study Locations
Locations
United States, Alabama
University of Alabama-Birmingham Recruiting
Birmingham, Alabama, United States
Contact: Dana Rigsby Golson    205-996-4015    ccnrn@uab.edu   
Contact: April Agne    205-996-4015    aagne@uab.edu   
Principal Investigator: Timothy Garvey         
Sub-Investigator: Andrea Cherrington         
United States, Arizona
Southwestern American Indian Center Recruiting
Phoenix, Arizona, United States
Contact: Tina Killean    602-200-5337    Tina.Killean@nih.gov   
Contact: Erica Joshevama    602-200-5337    erica.joshevama@nih.gov   
Principal Investigator: Jonathan Krakoff         
United States, California
Veterans Medical Research Foundation, San Diego (San Diego VA) Recruiting
San Diego, California, United States
Contact: Andrea Gasper    858-552-8585 ext 1431    amgasper@ucsd.edu   
Contact: Catherine Delue    858-552-8585 ext 6740    catherine.delue@va.gov   
Principal Investigator: Robert Henry         
United States, Colorado
University of Colorado Recruiting
Denver, Colorado, United States
Contact: Chantal Underkofler    303-399-8020 ext 2059    chantal.underkofler@ucdenver.edu   
Contact: Ryan Loesch    303-399-2020 ext 4055    ryan.loesch@ucdenver.edu   
Principal Investigator: Neda Rasouli         
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States
Contact: Patricia Gatcomb    203-764-8463    patricia.gatcomb@yale.edu   
Contact: Magalys Perez    203-752-5268    m.perez@fhchc.org   
Principal Investigator: William Tamborlane         
Sub-Investigator: Anne Camp         
United States, Florida
South Florida VA Foundation (Miami VA) Recruiting
Miami, Florida, United States
Contact: Miriam Gutt    305-575-7290    mgutt@miami.edu   
Contact: Lisset Oropesa    305-243-1473    oropesa07@gmail.com   
Principal Investigator: Hermes Flores         
Sub-Investigator: Jennifer Marks         
United States, Georgia
Atlanta VA Medical Center Recruiting
Decatur, Georgia, United States
Contact: Stephaine Raines    404-235-3024    tasha.raines@va.gov   
Contact: Cynthia Adams    404-235-3024    cynthia.adams1@va.gov   
Principal Investigator: Lawrence Phillips         
Kaiser Permanente of Georgia Recruiting
Duluth, Georgia, United States
Contact: Michelle Curtis       Michelle.D.Curtis@kp.org   
Contact: Bonita Hollis       bonita.a.hollis@kp.org   
Principal Investigator: Joshua Barzilay         
United States, Hawaii
Pacific Health Research and Education Institute (VA Pacific Islands) Recruiting
Honolulu, Hawaii, United States
Contact: Vicki Jenkins    808-564-5700    GRADE.VA@phrei.org   
Contact: Mike Matwichyna    808-564-5700    GRADE.VA@phrei.org   
Principal Investigator: Helen Petrovitch         
United States, Indiana
Indiana University School of Medicine Recruiting
Indianapolis, Indiana, United States
Contact: Tonya Hamilton    317-274-7679    tpinksto@iupui.edu   
Principal Investigator: Kieren Mather         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States
Contact: Laura Knosp    319-384-5369    laura-knosp@uiowa.edu   
Contact: Tamara Lowe    309-384-8103    tamara-lowe@uiowa.edu   
Principal Investigator: William Sivitz         
United States, Louisiana
Pennington Biomedical Research Center Recruiting
Baton Rouge, Louisiana, United States
Contact: Natalie Haynes    225-763-3000    clinicaltrials@pbrc.edu   
Principal Investigator: William Cefalu         
Tulane University Health Sciences Center Recruiting
New Orleans, Louisiana, United States
Contact: Bonnie Katalenich    504-988-6200    bkatalen@tulane.edu   
Principal Investigator: Vivian Fonseca         
United States, Maryland
MedStar Health Research Institute Recruiting
Hyattsville, Maryland, United States
Contact: Amy Smith Loveland    301-560-2915    GRADE@medstar.net   
Contact: Maria Hurtado    301-560-2915    GRADE@medstar.net   
Principal Investigator: Aroda Vanita         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States
Contact: Andrea deManbey    617-724-7851    GRADE@partners.org   
Contact: Rachel Kochis       GRADE@partners.org   
Principal Investigator: Deborah Wexler         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States
Contact: Becky Eggleston    855-566-6559    regglest@med.umich.edu   
Principal Investigator: William Herman         
Sub-Investigator: Rodica Pop-Busui         
United States, Minnesota
International Diabetes Center Recruiting
Minneapolis, Minnesota, United States
Contact: Renae Hill    952-993-9605    IDCresearch@parknicollet.com   
Contact: Sarah Borgman       IDCresearch@parknicollet.com   
Principal Investigator: Richard Bergenstal         
University of Minnesota Recruiting
Minneapolis, Minnesota, United States
Contact: Michael Mech    612-626-0143    GRADE@umn.edu   
Contact: Mary Coe    612-626-0143    GRADE@umn.edu   
Principal Investigator: Elizabeth Seaquist         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States
Contact: Carol Lynn Recklein    314-362-8608    crecklei@dom.wustl.edu   
Contact: Sarah Kissel    314-361-8614    skissel@dom.wustl.edu   
Principal Investigator: Janet McGill         
United States, Nebraska
University of Nebraska Recruiting
Omaha, Nebraska, United States
Contact: Grace Rodriguez    402-559-6244    mrodrigu@unmc.edu   
Principal Investigator: Cyrus Desouza         
United States, New Mexico
University of New Mexico School of Medicine Recruiting
Albuquerque, New Mexico, United States
Contact: Elizabeth Duran-Valdez    505-272-5454    Evaldez@salud.unm.edu   
Principal Investigator: David Schade         
United States, New York
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States
Contact: Janet Brown-Friday    718-839-7941    GRADE@einstein.yu.edu   
Contact: Entila Xhori    718-839-7941    GRADE@einstein.yu.edu   
Principal Investigator: Jill Crandall         
Sub-Investigator: Diane McKee         
State University of New York (SUNY)-Downstate Medical Center Recruiting
Brooklyn, New York, United States
Contact: Necole Brown    718-270-4693      
Contact: Mari Tsovian    718-670-14827    mat9150@nyp.org   
Principal Investigator: Mary Ann Benerji         
Sub-Investigator: Daniel Lorber         
Mount Sinai St. Luke's Hospital Recruiting
New York, New York, United States
Contact: Joseph Bastawrose    212-523-4171    jbastawrose@chpnet.org   
Principal Investigator: Xavier Pi-Sunyer         
Columbia University Naomi Berrie Diabetes Center Recruiting
New York, New York, United States
Contact: Patricia Kringas    212-851-5489    mpk40@columbia.edu   
Contact: Camille Hausheer    212-851-5449      
Principal Investigator: Robin Goland         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States
Contact: Jennifer E Jones    919-681-3574    jennifer.english@dm.duke.edu   
Principal Investigator: Jennifer Green         
University of North Carolina Diabetes Care Center Recruiting
Durham, North Carolina, United States
Contact: Juanita Cuffee    919-957-5693    juanita_cuffee@med.unc.edu   
Contact: Dawn Culmer    919-260-8850 ext 277    dculmer@email.unc.edu   
Principal Investigator: Sue Kirkman         
Sub-Investigator: John Buse         
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States
Contact: Kathy Burton    513-861-3100 ext 4715    kathy.burton@va.gov   
Contact: Colleen Rogge    513-475-6478    MaryColleen.Rogge@va.gov   
Principal Investigator: Robert Cohen         
Case Western Reserve University School of Medicine Recruiting
Cleveland, Ohio, United States
Contact: Margaret Titkin    216-231-3240      
Contact: Cindy Newman    216-778-3237      
Principal Investigator: Faramarz Ismail-Beigi         
Sub-Investigator: Corinna Falck-Ytter         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States
Contact: Trish Kirchhoff    503-494-4650    kirchhof@ohsu.edu   
Contact: Nancy Cady    503-494-4650    GRADE@ohsu.edu   
Principal Investigator: Andrew Ahmann         
United States, Texas
Baylor Endocrine Center Recruiting
Dallas, Texas, United States
Contact: Analyn Uy    214-820-4774    researchtrials@baylorhealth.edu   
Principal Investigator: Priscilla Hollander         
University of Texas-Southwestern Medical Center Recruiting
Dallas, Texas, United States
Contact: Luisa Morton    214-648-9733    luisa.morton@utsouthwestern.edu   
Contact: Laura O Walker       laura.osornio@utsouthwestern.edu   
Principal Investigator: Philip Raskin         
Baylor College of Medicine Recruiting
Houston, Texas, United States
Contact: Erica Gonzalez    713-798-3625      
Contact: Charlyne Wright    713-798-3625      
Principal Investigator: Ashok Balasubramanyam         
University of Texas Health Science Center Recruiting
San Antonio, Texas, United States
Contact: Hector Verastigui    210-358-7200      
Contact: R Irene Garza    210-358-7200      
Principal Investigator: Ralph DeFronzo         
United States, Washington
Seattle Institute for Biomedical and Clinical Research Recruiting
Seattle, Washington, United States
Contact: Brenda Montgomery    206-768-5338      
Contact: Christina Peterson    206-598-4978    cmiller1@uw.edu   
Principal Investigator: Kristina Utzschneider         
Sponsors and Collaborators
GRADE Study Group
Becton, Dickinson and Company
Bristol-Myers Squibb
Merck Sharp & Dohme Corp.
Novo Nordisk A/S
Hoffmann-La Roche
Sanofi
Investigators
Study Chair: David M Nathan, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: GRADE Study Group
ClinicalTrials.gov Identifier: NCT01794143     History of Changes
Other Study ID Numbers: GRADE, 1U01DK098246-01
Study First Received: February 13, 2013
Last Updated: September 10, 2014
Health Authority: United States: Data and Safety Monitoring Board

Keywords provided by GRADE Study Group:
Treatment of Type 2 diabetes
Comparative effectiveness research
Clinical trial
Patient-centered outcomes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin
Glargine
Liraglutide
Glimepiride
Insulin
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 18, 2014