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

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

Overview[ - collapse ][ - ]

Purpose	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%).
Condition	Diabetes Mellitus, Type 2 Diabetes
Intervention	Drug: Metformin Drug: Detemir Drug: Liraglutide Drug: Insulin Aspart
Phase	Phase 4
Sponsor	University of Texas Southwestern Medical Center
Responsible Party	University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier	NCT01966978
First Received	October 17, 2013
Last Updated	October 21, 2013
Last verified	October 2013

Tracking Information[ + expand ][ + ]

First Received Date	October 17, 2013
Last Updated Date	October 21, 2013
Start Date	January 2014
Estimated Primary Completion Date	December 2016
Current Primary Outcome Measures	Composite end-point [Time Frame: Week 26] [Designated as safety issue: Yes]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)
Current Secondary Outcome Measures	Mean change from randomization in A1c at week 26 [Time Frame: Week 0 (Randomization) , Week 26] [Designated as safety issue: No] Percentage of patients reaching target A1c of <7% at week 26 [Time Frame: Week 26] [Designated as safety issue: No] Percentage of patients reaching pre-specified "treatment failure" outcome [Time Frame: week 13] [Designated as safety issue: No]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] [Designated as safety issue: No] Percentage of patients who lost 5% or more of body weight from randomization [Time Frame: Week 0 (Randomization) , Week 26] [Designated as safety issue: No] Hypoglycemic episodes [Time Frame: Week 0 (Randomization) , Week 2, week 4, week 13, Week 26] [Designated as safety issue: Yes]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] [Designated as safety issue: Yes]Percentage of patients experiencing any hypoglycemic episode (BG < 70) Diabetes Quality of Life (DQOL)questionnaire score [Time Frame: Week 0 (Randomization) , Week 26] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No] Health care cost, total [Time Frame: Week 0 (Randomization) , Week 26] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No] Number of titration events by patient [Time Frame: Week 0 (Randomization) , Week 26] [Designated as safety issue: No] Healthcare provider time during scheduled office (minutes/visit) [Time Frame: Week 0 (Randomization) , Week 26] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: Yes]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

Descriptive Information[ + expand ][ + ]

Brief Title	The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study
Official Title	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
Brief Summary	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%).
Detailed Description	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.
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Diabetes Mellitus, Type 2 Diabetes
Intervention	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 Names: Metformin tabletsDrug: 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 Names: Insulin Detemir subcutaneous once or twice dailyDrug: 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 Names: Liraglutide 6 mg/mL SubcutaneouslyDrug: 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 Names: Insulin Aspart Subcutaneous injection one to three times daily
Study Arm (s)	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 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)

Recruitment Information[ + expand ][ + ]

Recruitment Status	Not yet recruiting
Estimated Enrollment	100
Estimated Completion Date	December 2016
Estimated Primary Completion Date	June 2016
Eligibility Criteria	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.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Marconi Abreu, MD 214-648-8479 marconi.abreu@phhs.org
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01966978
Other Study ID Numbers	STU 072013-030
Has Data Monitoring Committee	No
Information Provided By	University of Texas Southwestern Medical Center
Study Sponsor	University of Texas Southwestern Medical Center
Collaborators	Not Provided
Investigators	Principal Investigator: Ildiko Lingvay UT Southwestern Medical Center
Verification Date	October 2013

Locations[ + expand ][ + ]