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The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study (SIMPLE)

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ClinicalTrials.gov Identifier: NCT01966978
Recruitment Status : Completed
First Posted : October 22, 2013
Last Update Posted : April 12, 2018
Sponsor:
Information provided by (Responsible Party):
Ildiko Lingvay, University of Texas Southwestern Medical Center

October 17, 2013
October 22, 2013
April 12, 2018
November 2014
December 2017   (Final data collection date for primary outcome measure)
Mean change from randomization in A1c at week 26 [ Time Frame: Week 26 ]
Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy
Composite end-point [ Time Frame: Week 26 ]
Percentage of patients with glycosylated Hemoglobin A1c (A1c)<7% AND no documented severe hypoglycemia (<56 mg/dL) during the study AND no significant weight gain (>3% from baseline)
Complete list of historical versions of study NCT01966978 on ClinicalTrials.gov Archive Site
  • Composite end-point [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Percentage of patients with glycosylated Hemoglobin A1c (A1c)<7% AND no documented severe hypoglycemia (<56 mg/dL) during the study AND no significant weight gain (>3% from baseline)
  • Percentage of patients reaching target A1c of <7% at week 26 [ Time Frame: Week 26 ]
  • Percentage of patients reaching pre-specified "treatment failure" outcome [ Time Frame: week 13 ]
    Treatment Failure defined as A1c>10% at week 13 (visit 5)
  • Mean change from randomization in body weight [ Time Frame: Week 0 (Randomization) , Week 26 ]
  • Percentage of patients who lost 5% or more of body weight from randomization [ Time Frame: Week 0 (Randomization) , Week 26 ]
  • Hypoglycemic episodes [ Time Frame: Week 0 (Randomization) , Week 2, week 4, week 13, Week 26 ]
    Number of hypoglycemic episodes defined as mild (symptoms of hypoglycemia confirmed by a CBG reading of <70 mg/dl), moderate (any CBG reading <56 mg/dl), severe (need for help to recover regardless of CBG reading
  • Percentage of patients experiencing any hypoglycemic episode [ Time Frame: Week 0 (Randomization) , Week 2, week 4, week 13, Week 26 ]
    Percentage of patients experiencing any hypoglycemic episode (BG < 70)
  • Diabetes Quality of Life (DQOL)questionnaire score [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Diabetes Quality of Life (DQOL) questionnaires will be completed by the patient at the randomization and end-of study visits
  • Short Form-36 (SF-36) questionnaire score [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Quality of life questionnaires will be completed by the patient at the randomization and end-of study visits
  • Number of daily injections [ Time Frame: Week 0 (Randomization) , Week 26 ]
  • 7-point glucose profiles over 2 consecutive days [ Time Frame: Week 0 (Randomization) , Week 26 ]
    7-point glucose profiles (pre-breakfast, 2h after breakfast, pre lunch, 2 hours after lunch, pre dinner, 2 hours after dinner and bedtime)over 2 consecutive days performed the week prior to the randomization visit and the week prior to the week 26 visit
  • Mean change from randomization in A1c at week 26 [ Time Frame: Week 0 (Randomization) , Week 26 ]
  • Percentage of patients reaching target A1c of <7% at week 26 [ Time Frame: Week 26 ]
  • Percentage of patients reaching pre-specified "treatment failure" outcome [ Time Frame: week 13 ]
    Treatment Failure defined as A1c>10% at week 13 (visit 5)
  • Mean change from randomization in body weight [ Time Frame: Week 0 (Randomization) , Week 26 ]
  • Percentage of patients who lost 5% or more of body weight from randomization [ Time Frame: Week 0 (Randomization) , Week 26 ]
  • Hypoglycemic episodes [ Time Frame: Week 0 (Randomization) , Week 2, week 4, week 13, Week 26 ]
    Number of hypoglycemic episodes defined as mild (symptoms of hypoglycemia confirmed by a CBG reading of <70 mg/dl), moderate (any CBG reading <56 mg/dl), severe (need for help to recover regardless of CBG reading
  • Percentage of patients experiencing any hypoglycemic episode [ Time Frame: Week 0 (Randomization) , Week 2, week 4, week 13, Week 26 ]
    Percentage of patients experiencing any hypoglycemic episode (BG < 70)
  • Diabetes Quality of Life (DQOL)questionnaire score [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Diabetes Quality of Life (DQOL) questionnaires will be completed by the patient at the randomization and end-of study visits
  • Short Form-36 (SF-36) questionnaire score [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Quality of life questionnaires will be completed by the patient at the randomization and end-of study visits
  • Number of daily injections [ Time Frame: Week 0 (Randomization) , Week 26 ]
  • Health care cost, total [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Healthcare costs will be extracted from the billing interface of the electronic medical record. As the study is conducted in a closed medical system, all patient related charges are captured, including medications, visits, ER visits inpatient hospitalizations, medications, labs, etc. After receiving a detailed report of these charges, the investigator will manually determine the diabetes-related designation for each charge. Pharmacy, versus laboratory, outpatient professional/facility, inpatient professional/facility charges can also be categorized based on the report.
  • Health care cost, diabetes-related [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Healthcare costs will be extracted from the billing interface of the electronic medical record. As the study is conducted in a closed medical system, all patient related charges are captured, including medications, visits, ER visits inpatient hospitalizations, medications, labs, etc. After receiving a detailed report of these charges, the investigator will manually determine the diabetes-related designation for each charge. Pharmacy, versus laboratory, outpatient professional/facility, inpatient professional/facility charges can also be categorized based on the report.
  • Number of titration events by healthcare professional [ Time Frame: Week 0 (Randomization) , Week 26 ]
  • Number of titration events by patient [ Time Frame: Week 0 (Randomization) , Week 26 ]
  • Healthcare provider time during scheduled office (minutes/visit) [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Healthcare providers will time each patient visit and each non-scheduled office/telephone encounter, using an unobtrusive digital timer not noticeable to the patient
  • Healthcare provider time, unscheduled (total minutes) [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Healthcare providers will time each patient visit and each non-scheduled office/telephone encounter, using an unobtrusive digital timer not noticeable to the patient
  • Compliance with pharmacologic therapy [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Patient compliance will be assessed by direct counting of the used/unused dispensed product and pharmacy dispensing records
  • Change in LDL cholesterol from baseline to week 26 [ Time Frame: Week 0 (Randomization) , Week 26 ]
    change in LDL cholesterol from baseline(within 3 months from randomization) to week 26
  • Change in triglycerides from baseline [ Time Frame: Week 0 (Randomization) , Week 26 ]
    Change in triglycerides from baseline ( within 3 months from randomization)and at week 26
  • 7-point glucose profiles over 2 consecutive days [ Time Frame: Week 0 (Randomization) , Week 26 ]
    7-point glucose profiles (pre-breakfast, 2h after breakfast, pre lunch, 2 hours after lunch, pre dinner, 2 hours after dinner and bedtime)over 2 consecutive days performed the week prior to the randomization visit and the week prior to the week 26 visit
Not Provided
Not Provided
 
The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study
The Effect of Simple Insulin Detemir Titration, Metformin Plus Liraglutide Compared to Simple Insulin Detemir Titration Plus Insulin Aspart and Metformin for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study: A 26 Week, Randomized, Open Label, Parallel-group, Intention to Treat Study
The aim of this clinical trial is to assess and compare the effect of insulin detemir in combination with liraglutide and metformin versus insulin detemir in combination with insulin aspart and metformin in subjects with very uncontrolled Type 2 Diabetes (A1c > 10%).
The aim of this study is to compare a GLP-1 plus basal insulin and metformin treatment regimen to a basal-bolus plus metformin treatment regimen in patients with very uncontrolled (HbA1c>10%) type 2 diabetes. The investigators will compare the two regimens with respect to efficacy in improving glycemic control, rate of hypoglycemia, change in weight, effect on patient quality of life, treatment burden, physician time, as well as healthcare related cost. The investigators hypothesize that at 26 weeks from randomization the two treatment regimens will have similar percentage of patients reaching A1c levels <7.0%, while more patients on the GLP-1 plus basal insulin strategy will achieve the composite end point of A1c levels <7.0% without severe hypoglycemia or significant weight gain.
Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Diabetes Mellitus, Type 2
  • Diabetes
  • Drug: Metformin
    Metformin will be started at 500 mg daily (or continued at current dose)and weekly titrated to 2000 mg or maximum tolerated dose (at least 1000 mg/day)
    Other Name: Metformin tablets
  • Drug: Detemir
    Insulin detemir will be started in both groups at 0.3 units/kg or conversion 1:1 from dose of basal insulin prior to randomization. The titration will be primarily patient-driven, based on our study protocol table. Additional physician driven titration will be allowed in both groups if patient fails to intensify basal insulin dose as directed.
    Other Name: Insulin Detemir subcutaneous once or twice daily
  • Drug: Liraglutide
    Initial dose of 0.6 mg/day with weekly increments of 0.6 mg until dose of 1.8 mg/day or maximal tolerated dose (at least 1.2 mg/day)is reached
    Other Name: Liraglutide 6 mg/mL Subcutaneously
  • Drug: Insulin Aspart
    Insulin aspart will be initiated at a dose of 0.3 units/kg/day divided among the number of meals taken daily and titrated based on physician clinical judgment with the goal of pre-prandial BG 70-130 mg/dL and post-prandial BG <180
    Other Name: Insulin Aspart Subcutaneous injection one to three times daily
  • Active Comparator: Control: Metformin, Insulin Detemir, Insulin Aspart
    Metformin titrated to max tolerated dose (at least 1000 mg/day); Insulin detemir titrated based on the study protocol; Insulin Aspart titrated by the physician
    Interventions:
    • Drug: Metformin
    • Drug: Detemir
    • Drug: Insulin Aspart
  • Active Comparator: Metformin, insulin determir, Liraglutide
    Metformin titrated to max tolerated dose (at least 1000mg/day); Insulin detemir titrated based on the study protocol"; Liraglutide titrated to max tolerated dose (at least 1.2 mg/day)
    Interventions:
    • Drug: Metformin
    • Drug: Detemir
    • Drug: Liraglutide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
157
100
December 2017
December 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

1. Clinical diagnosis of type 2 diabetes with confirmed HbA1c level >10% at time of enrollment, regardless of prior or current treatment regimens, or time since diagnosis.

Exclusion Criteria:

  1. Age <18 as the feasibility and safety of this treatment regimen should be first established in the adult population; if successful, a subsequent pediatric study will be proposed;
  2. Type 1 diabetes as purposefully withholding meal-time insulin is contraindicated;
  3. Clinical state requiring inpatient admission/treatment;
  4. Contraindication or strong cautions to any of the study medications:

    1. Creatinine above 1.4 mg/dl for women and 1.5 mg/dl for men (per metformin label)
    2. History of lactic acidosis (per metformin label)
    3. Advanced hepatic or cardiac disease (per metformin label)
    4. Age >80 years (per metformin label)
    5. Chronic alcohol use (>14 drinks/week)
    6. History of pancreatitis (per liraglutide label)
    7. Personal or family history of medullary thyroid cancer or MEN syndrome (per liraglutide label)
    8. Pregnancy and lactation (per liraglutide label)
  5. Any serious or unstable medical condition as it would interfere with treatment assignment as well as outcome measurement;
  6. Any scheduled elective procedures/surgeries;
  7. Active infections, including osteomyelitis;
  8. Not willing to participate, unable to keep projected appointments, unwillingness to receive injectable treatment; unwillingness to perform 7-point glucose profiles over 2 consecutive days the weeks prior to Randomization (visit 1)and the week prior to visit 6
  9. Non English speaking.
Sexes Eligible for Study: All
18 Years to 80 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01966978
STU 072013-030
No
Not Provided
Not Provided
Ildiko Lingvay, University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center
Not Provided
Principal Investigator: Ildiko Lingvay UT Southwestern Medical Center
University of Texas Southwestern Medical Center
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP