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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2013 by University of Texas Southwestern Medical Center
Sponsor:
Information provided by (Responsible Party):
Ildiko Lingvay, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01966978
First received: October 17, 2013
Last updated: October 21, 2013
Last verified: October 2013
  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 Intervention Phase
Diabetes Mellitus, Type 2
Diabetes
Drug: Metformin
Drug: Detemir
Drug: Liraglutide
Drug: Insulin Aspart
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

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)


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


Estimated Enrollment: 100
Study Start Date: January 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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: 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: 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)
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01966978

Contacts
Contact: Marconi Abreu, MD 214-648-8479 marconi.abreu@phhs.org
Contact: Laura Golici, BA 214-648-2515 Laura.golici@utsouthwestern.edu

Locations
United States, Texas
UT Southwestern Medical Center Not yet recruiting
Dallas, Texas, United States, 02720
Contact: Marconi Abreu, MD    214-648-8479    marconi.abreu@phhs.org   
Contact: Laura Golici, BA    214-648-2515    laura.golici@utsouthwestern.edu   
Principal Investigator: Ildiko Lingvay, MD         
Sub-Investigator: Marconi Abreu, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Ildiko Lingvay UT Southwestern Medical Center
  More Information

No publications provided

Responsible Party: Ildiko Lingvay, MD, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01966978     History of Changes
Other Study ID Numbers: STU 072013-030
Study First Received: October 17, 2013
Last Updated: October 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:
Insulin
Insulin, Long-Acting
Insulin, Short Acting
Diabetes Mellitus, Type 2
Detemir
Liraglutide
GLP-1
Glucagon Like Peptide
Metformin
Uncontrolled Diabetes
Elevated A1c
Incretins

Additional relevant MeSH terms:
Insulin, Globin Zinc
Insulin
Insulin Aspart
Insulin, Long-Acting
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liraglutide
Metformin
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 16, 2014