Study to Compare Efficacy of the MiniMed Paradigm REAL-Time System Vs. MDI in Subjects Naive to Insulin Pump Therapy (STAR3)

The STAR 3 Study - A Prospective, Randomized, Two-Arm Study to Compare the Efficacy of the MiniMed Paradigm REAL-Time System Versus Multiple Daily Injections (MDI) in Subjects Naïve to Insulin Pump Therapy

Primary Outcomes: Average decrease in A1c from baseline to end of Study Phase (52 weeks) for subjects in the "722 Group" is greater than that for subjects in the "Control (MDI) Group".

Secondary Outcomes: Incidence and frequency of severe hypoglycemia; Measure of glycemic variability, Area Under the Curve (AUC); Quality of Life; and Health Economic Outcomes (MRU)

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: MiniMed Paradigm REAL-Time System

Detailed Description

Glycemic control remains a significant challenge for adult, adolescent and pediatric Type 1 diabetics. The current first line standard of care continues to be MDI therapy utilizing a long acting analog insulin. Continuous Glucose Monitoring (CGMS) is currently used by clinicians to record continuous, retrospective glucose measurements, which aid in identification of glycemic excursion patterns. This data is then used to make future therapy change recommendations. The MiniMed Paradigm REAL-Time System transmits real-time glucose measurements to the insulin pump every 5 minutes, allowing users to view their current glucose values, as well as to review glycemic excursions and trends over a 24-hour period. Additionally, data can be downloaded from the monitor to a personal computer, using appropriate software, so that the patient and physician can see a complete picture of glucose trends over time. The System will also alert users of high and low glucose levels, and allow subjects and their clinicians to treat to a therapeutic target HbA1c under carefully monitored conditions.

Subjects wearing the MiniMed Paradigm REAL-Time System will be compared to subjects that continue on their current MDI therapy, that includes a long acting analog insulin, over a 12 month period to evaluate changes in glycemic control (HbA1c).

• Study Type: Interventional
• Enrollment (Actual): 485
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6E1M7
      • Endocrine Research, Inc.
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B3V6
      • Health Science Center Memorial Hospital of Newfoundland
  • Ontario
    • Kingston, Ontario, Canada, K7M5L2
      • Kingston General Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital - UHN
• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Institute
    • Orange, California, United States, 92864-3874
      • Children's Hospital of Orange County (CHOC)
  • Colorado
    • Boulder, Colorado, United States, 80045
      • Barbara Davis Center, University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06522
      • Yale University
  • Florida
    • Miami, Florida, United States, 33136
      • Diabetes Research Institute (DRI)
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc.
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Diabetes and Osteoporosis Center
  • Kansas
    • Wichita, Kansas, United States, 67211
      • Mid-America Diabetes Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Kentucky Diabetes Endocrinology Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Clinic
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • DeVos Children's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Louis Park, Minnesota, United States, 55416
      • Minnesota International Diabetes Center
    • Saint Paul, Minnesota, United States, 55102
      • Children's Hospital of St. Paul
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • Rochester, New York, United States, 14644
      • University of Rochester
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Diabetes & Endocrine Center
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Diabetes Research Clinic
    • Greenville, North Carolina, United States, 27834
      • Diabetes and Obesity Center, East Carolina University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Utah Diabetes Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53717
      • University of Wisconsin Health West

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 7 to 70 years
• Has been treated by the Principal Investigator or referring physician within the same practice for at least six months prior to screening
• Is fluent in speaking, reading and understanding English
• Has Type 1 diabetes mellitus, diagnosed by c-peptide, insulin antibodies, or prior documented DKA, or by a clinical picture consistent with Type 1 diabetes and excluding type 2 diabetes i.e. - previous ketosis as evidenced by laboratory evidence of urine ketones or alteration in bicarbonate levels with corresponding increased glucose levels, diagnosed at least 6 months prior to study entry, or has a fasting C-peptide that meet criteria of 110% of lower limit of normal or 200% of lower limit of normal in the presence of renal insufficiency (creatinine clearance < 50ml/min) at screening
• Is insulin infusion pump naїve or has not used an insulin pump within the last three years
• Currently is treated with insulin administration by injection > (greater or equal to) three (3) times daily and therapy has included the use of a long acting analog insulin for at least the previous 3 months prior to screening
• Performs fingerstick blood glucose (BG) testing an average of four times per day in the 30 days prior to screening
• Within 6 months prior to study entry and at Screening Visit 1, subject has a documented A1c level =/> 7.4% and =/< 9.5%

Exclusion Criteria:

• Is pregnant or planning to become pregnant during the course of the study
• Has suffered two or more documented events of severe hypoglycemia without warning of impending low glucose levels, within the previous 12 months
• Currently using oral or injectable steroids or immunosuppressant medications
• Use of any other pharmaceutical agent, other than insulin to treat diabetes, within the three months prior to screening;
• Has a current history of alcohol or drug abuse
• Has a history of myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack (TIA), cerebrovascular accident (CVA), or thromboembolic disease in the 3 months prior to screening
• Has uncontrolled hypertension (diastolic blood pressure >100 mmHg and/or sustained systolic level [3 successive readings] > 160). Subjects who are taking antihypertensive medication will not be excluded provided they are maintained at a stable dose for 3 months prior to screening
• Has serious or unstable medical or psychological conditions (e.g., eating disorders, clinical depression, anxiety disorder) which, in the opinion of the Investigator, would compromise the subject's safety or successful participation in the study
• Is undergoing renal dialysis, including hemodialysis and continuous ambulatory peritoneal dialysis (CAPD)
• Has evidence of any allergic dermatological condition (e.g., severe adhesive sensitivity)
• Has recurrent episodes of skin infections or history of staphylococcus infection carrier state
• Has potential for lack of compliance or any other issue that may preclude the subject from satisfactory participation in the study, based on Investigatory judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 722 sensor augmented pump; 722 arm: MiniMed Paradigm REAL-Time System using NovoLog/NovoRapid for 1 year	Device: MiniMed Paradigm REAL-Time System; Paradigm 722 insulin pump Paradigm REAL-Time Transmitter Sensor ComLink Paradigm Link glucose meter; Other Names: Medtronic Paradigm REAL-Time System
No Intervention: Multiple Daily Injections (MDI); MDI arm: Continue with current MDI therapy using Lantus and NovoLog/NovoRapid for 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in A1c From Baseline to 52 Weeks	Change is defined as A1c at Week 52 minus A1c at Baseline in each study arm. The difference between the change in each group will then be analyzed. A1c measure is defined as the percent of glycated hemoglobin using one standardized assay for all subjects.	Baseline and 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Frequency of Severe Hypoglycemia From Baseline to Week 52;	Severe Hypoglycemia is defined as a hypoglycemic episode absolutely requiring assistance from another person and preferably accompanied by a confirmatory Blood Glucose (BG) by finger stick of less than 50 mg/dL (2.8 mmol/L). The frequency evaluates the total number of events. This will be analyzed and compared between the two study arms from baseline to week 52.	Baseline and 52 weeks
Overall Difference in Rate of Severe Hypoglycemia Events Between Study Arms From Baseline to Week 52	Severe Hypoglycemia is defined as a hypoglycemic episode absolutely requiring assistance from another person and preferably accompanied by a confirmatory BG by finger stick of less than 50 mg/dL (2.8 mmol/L). The rate evaluates the number of participants that experienced at least one severe hypoglycemia event and compares this number between the two study arms from Baseline to week 52. This measure identifies the rate or frequency of unique participant events.	Baseline and 52 weeks
Changes in Hypoglycemia Area Under the Curve (AUC) From Baseline to Week 52;	Hypoglycemia is defined as a recorded blood glucose event <70mg/dL. The amount of time spent below this parameter will be analyzed and compared between groups from Baseline to Week 52.	Baseline and 52 weeks
Changes From Baseline in Hyperglycemia Area Under the Curve (AUC) From Baseline to Week 52	Hyperglycemia is defined as a recorded blood glucose event > 180 mg/dL. The amount of time spent above this parameter will be analyzed and compared between groups from Baseline to Week 52.	Baseline and 52 weeks
Quality of Life - Hypoglycemia Fear Scale (HFS), Overall Score	Difference of Baseline and 52 Weeks in Hypoglycemia Fear Scale (HFS) Overall Score between the two study arms (adult subjects only) is presented. Both baseline and 52 weeks scores range from 0-100, with lower scores suggest higher satisfaction. Therefore, a negative number in the difference suggests higher satisfaction at 52 Weeks than Baseline.	Baseline and 52 weeks
Health Economic Outcome	Health Economic Outcome was a cost-effectiveness analysis combining estimates from the trial and the literature to populate the previously validated Center for Outcomes Research (CORE) Diabetes Model. Results represent the use of 3-day sensors. This analysis was restricted to only adult subjects (Age 19 to 70), therefore the number of participant analyzed is different. The goal was to estimate the long term cost effectiveness of Sensor Augmented Pump therapy from the perspective of the US health care system. The unit of measurement was cost in $ per year for sensor augmented pump group and MDI group. No formal statistical analysis was planned or performed	Baseline and 52 weeks
Quality of Life - Short Form-36 (SF-36v2™), General Health	Difference of Baseline and 52 Weeks in Short Form-36 (SF-36v2™), General Health, between the two study arms (adult subjects only) is presented. Both baseline and 52 weeks scores range from 0-100, with higher scores suggest higher satisfaction. Therefore, a positive number in the difference suggests higher satisfaction at 52 Weeks than Baseline.	Baseline and 52 Weeks
Quality of Life - Insulin Delivery System Rating Questionnaire (IDSRQ) for Subject Satisfaction With Type of Insulin Therapy	Difference of Baseline and 52 Weeks in Insulin Delivery System Rating Questionnaire (IDSRQ) for Subject Satisfaction with Type of Insulin Therapy, between the two study arms is presented. Both baseline and 52 weeks scores range from 0-100, with higher scores suggest higher satisfaction. Therefore, a positive number in the difference suggests higher satisfaction at 52 Weeks than Baseline.	Baseline and 52 Weeks

Collaborators and Investigators

• Sponsor: Medtronic Diabetes
• Investigators: Principal Investigator: Stephen N Davis, MD, University of Maryland School of Medicine; Principal Investigator: William V Tamborlane, MD, Yale University; Study Director: Scott W Lee, MD, Medtronic Minimed

Publications and helpful links

General Publications

• Perkins BA, Halpern EM, Orszag A, Weisman A, Houlden RL, Bergenstal RM, Joyce C. Sensor-augmented pump and multiple daily injection therapy in the United States and Canada: post-hoc analysis of a randomized controlled trial. Can J Diabetes. 2015 Feb;39(1):50-4. doi: 10.1016/j.jcjd.2014.03.003. Epub 2014 Aug 29.
• Bergenstal RM, Tamborlane WV, Ahmann A, Buse JB, Dailey G, Davis SN, Joyce C, Peoples T, Perkins BA, Welsh JB, Willi SM, Wood MA; STAR 3 Study Group. Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N Engl J Med. 2010 Jul 22;363(4):311-20. doi: 10.1056/NEJMoa1002853. Epub 2010 Jun 29. Erratum In: N Engl J Med. 2010 Sep 9;363(11):1092.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: January 2, 2007
• First Submitted That Met QC Criteria: January 2, 2007
• First Posted (Estimate): January 4, 2007

Study Record Updates

• Last Update Posted (Actual): May 23, 2018
• Last Update Submitted That Met QC Criteria: May 22, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Glycemic control; Sensor
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CEP179/Z25