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

Study Overview
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Brief Summary
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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)

Detailed Description
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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).

Official Title
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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

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: MiniMed Paradigm REAL-Time System


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glycemic control, Sensor