Inpatient Evaluation of an Automated Closed-Loop Control-to-Range System

Study Overview
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Brief Summary
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The purpose of this study is to test an insulin management system (Control-to-Range (CTR) system) in an inpatient setting to see if the system is safe and effective enough to test in a future at-home study. The system includes (1) a DexCom Seven Plus Continuous Glucose Monitoring (CGM) device that measures the blood sugar, (2) a laptop computer that determines how much insulin is needed, and (3) an Insulet OmniPod insulin pump that delivers the insulin. The study will include two hospital stays consisting of meals and exercise scenarios. Both hospital stays will be for 24+ hours during the day and night. The study will include about 50 individuals at 7 clinical centers in the United States, France, Israel, and Italy.

Detailed Description
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Clinical Research Center (CRC) Session Detail (closed-loop control active for all elements) Day 1 (24+ hours): Admission at 7:00 AM Standardized breakfast with normal bolus at 9:00 AM Lunch with normal bolus at 1:00 PM Dinner with normal bolus at 7:00 PM Overnight sleep Breakfast with missed meal bolus followed by user alert and correction bolus Discharge Day 2 (24+ hours): Admission at 7:00 AM Standardized breakfast with normal bolus at 9:00 AM Lunch with normal bolus at 1:00 PM Exercise Dinner with normal bolus at 7:00 PM Overnight sleep Breakfast with overbolus at 7:00 AM Discharge Meal boluses will be semi-automated, with manual meal announcement by the physician/nurse, automated bolus recommendation by the system, and automated delivery of the bolus following confirmation of the recommendation. Between-meal insulin dosing will be fully automated; bolus confirmation by the physician/nurse will be requested by the closed-loop controller only when it determines that carbohydrates may be necessary to avoid hypoglycemia following the bolus.

Official Title
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Inpatient Evaluation of an Automated Closed-Loop Control-to-Range System

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Control-to-Range Automated Insulin Management System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of type 1 diabetes for at least one year and using an insulin pump for at least 6 months The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed. Age 12 to 65 years Hemoglobin A1c (HbA1c) between 5.0% and 10.5%, as measured with DCA2000 or equivalent device For females, not currently known to be pregnant Demonstration of proper mental status and cognition for the study An understanding of and willingness to follow the protocol and sign the informed consent or assent Exclusion Criteria: Diabetic ketoacidosis in the past 6 months Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment History of a seizure disorder (except hypoglycemic seizure). Subjects with a history of seizures may be included in the study if they receive written clearance from their neurologist treatment for a seizure disorder Coronary artery disease or heart failure. Subjects with a history of coronary artery disease may be included in the study if they receive written clearance from their cardiologist Cystic fibrosis Active infection A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples: Inpatient psychiatric treatment in the past 6 months for either the subject or the subject's primary care giver (i.e., parent or guardian) Presence of a known adrenal disorder Abnormal liver or renal function (Transaminase >2 times the upper limit of normal, Creatinine > 1.5 mg/dL) Active gastroparesis If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study Uncontrolled thyroid disease Abuse of alcohol Note: Adequately treated thyroid disease and celiac disease do not exclude subjects from enrollment A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the exercise protocol Current use of a beta blocker medication Hematocrit <30% (labs drawn at screening visit or within one month prior to screening for other purposes will suffice for enrollment purposes related to hematocrit) Use of pseudoephedrine 48 hours prior to Clinical Research Center (CRC) admission

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Closed-Loop Control<br>The Control to Range algorithm will be used in conjunction with continuous glucose monitoring and insulin pump delivery to manage the subject's blood glucose. | Device: Control-to-Range Automated Insulin Management System<br>* The devices that will be used in the Closed-Loop Control System are standardized across all study sites and include the DexCom Seven Plus Continuous Glucose Monitor (CGM), the OmniPod insulin pump, and the FreeStyle blood glucose meter. The Closed-Loop Control System will be used during all 3 admission visits.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of glucose values 71-180 mg/dL of combined day and night readings during the first admission visit | Group success criterion defined as a mean blood glucose >50%, lower end of one-sided 95% confidence interval >40% and individual criterion of no individual <30%. | Admission Visit 1 | 
| Percent of subjects with blood glucose reading of 71-180 mg/dL 4 hours following the breakfast with a missed meal bolus | Success is defined as >=40% subjects with a blood glucose in the 71-180 mg/dL range. | 4 hours following the breakfast with a missed meal bolus | 
| Percent of subjects with blood glucose reading of 71-180 mg/dL 5 hours following the breakfast with a meal bolus 30% more than the recommended bolus amount | Success is defined as >=50% subjects with a blood glucose in the 71-180 mg/dL range. | 5 hours following the breakfast with a meal bolus 30% more than the recommended bolus amount | 
| Percent of subjects with a blood glucose nadir <=60 mg/dL following exercise | Success is defined as less than 25% of subjects with a blood glucose nadir <=60 mg/dL. | Following exercise completion | 
| Overall frequency of hypoglycemia | Success defined as no subjects with severe hypoglycemia with a low blood glucose resulting in seizure, unconsciousness or the inability to treat oneself. | Includes both admission visits | 
| Overall frequency of hyperglycemia | Success defined as no subjects with diabetic ketoacidosis (DKA). | Includes both admission visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of blood glucose values 71-180 mg/dL during the day (9:00AM-11:00PM) of the first admission visit | Group success criterion defined as a mean blood glucose >50%, lower end of one-sided 95% confidence interval >40% and individual criterion of no individual <30%. | Admission Visit Day 1 (9:00AM-11:00PM) | 
| Percent of blood glucose values 70-180 mg/dL during the night (11:00PM-8:00AM) of the first admission visit | Group success criterian defined as a mean blood glucose >60%, lower end of one-sided 95% confidence interval >50% and individual criterion of no individual <30%. | Admission Visit Night 1 (11:00PM-8:00AM) | 
| Percent of blood glucose values >400 mg/dL during the first admission visit | Individual success is defined as no blood glucose values >400 mg/dL. | Admission Visit 1 | 
| Percent of blood glucose values <=60 mg/dL during the first admission visit | No more than 33% of visits with blood glucose <=60 mg/dL | Admission Visit 1 | 
| Percent of subjects with a peak blood glucose >400 mg/dL following the breakfast with a missed meal bolus | Success is defined as less than 5% of subjects have a peak blood glucose >400 mg/dL | 4 hours following the breakfast with a missed meal bolus | 
| Percent of subjects with a nadir blood glucose <=60 mg/dL following the breakfast with a missed meal bolus | Success is defined as less than 15% of subjects have a nadir blood glucose <=60 mg/dL | 4 hours following the breakfast with a missed meal bolus | 
| Percent of subjects with a peak blood glucose >400 mg/dL following the breakfast with a meal bolus 30% more than the recommended bolus amount | Success is defined as less than 5% of subjects have a peak blood glucose >400 mg/dL | following the breakfast with a meal bolus 30% more than the recommended bolus amount | 
| Percent of subjects with a nadir blood glucose <=60 mg/dL following the breakfast with a meal bolus 30% more than the recommended bolus amount | Success is defined as less than 25% of subjects have a nadir blood glucose <=60 mg/dL | following the breakfast with a meal bolus 30% more than the recommended bolus amount |