Outpatient Pump Shutoff Pilot Feasibility and Efficacy Study

Study Overview
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Brief Summary
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The purpose of this study is to see whether low blood sugar at night can be reduced by using a system that turns off the insulin pump automatically. The study system includes a combination continuous glucose monitor (CGM)/ insulin pump made by Medtronic MiniMed, Inc and a regular laptop computer that runs a computer program that predicts low blood sugar. It works by (1) measuring the glucose levels under the skin with a continuous glucose monitor, (2) using a computer program on a laptop to predict what will happen to the glucose level over the next 35-55 minutes, and (3) turning off the insulin pump when the computer program predicts that low blood sugar will occur. This study has several phases and will take about 3 months for a patient to complete. Patients will use the Medtronic CGM with the Enlite sensor at home for 10-15 days to be sure that they are able and willing to use this system and to determine if they meet the investigators study criteria to proceed with the next phase of the study. Patients will be provided teaching on how to use CGM data in real time. If a patient is not using a Medtronic CGM already, the patient will first use one at home for 10-15 days to be sure that he/she is able and willing to use it. If a patient is already using a Medtronic CGM, then his/her most recent 10-15 days of data will be used to find out if he/she is eligible. Those who need to complete the CGM run-in phase will have an extra office visit for training. If eligible to continue in the study, patients will need to use the study system for 5 nights at home so that the investigators can make sure they are able to use it correctly. After that, patients will be asked to use the study system each night for an additional 6 to 8 weeks. If the system is active and predicts that a patient's blood sugar will become low, the insulin pump will shut off for up to 2 hours. The study will include about 45 individuals at 3 clinical centers in the United States and Canada.

Detailed Description
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Patients who are eligible for the clinical trial initially will use a Medtronic Continuous Glucose Monitor (CGM) at home to verify that the subject is able to use the CGM and insert sensors. Subjects already using a Medtronic CGM will skip this phase, provided that the eligibility criteria for CGM use and the study are met. Patients who meet criteria for sensor use and the study will then use the closed-loop system at home for 5 days to demonstrate their ability to use the system and submit study data to the Coordinating Center. Patients who successfully demonstrate their ability to use the system at home as described above will be eligible for the randomized trial phase. This phase consists of use of the full system as an outpatient for approximately 42 nights: Each night the blood glucose level will be checked with the study home blood glucose (BG) meter and used to perform a calibration of the CGM. This calibration must occur no more than 90 minutes prior to activation of the system. NOTE: Patients will be instructed to calibrate the CGM per manufacturer guidelines. Then the system will be activated, linking the CGM and insulin pump to the computer at the bedside. A randomization schedule on the laptop will be used to determine whether the 'pump shut off' application will be active that night or not. Patients will be blinded as to whether the pump shut off is active when a session is initiated each night. There will not be an alarm if the pump shuts off. The CGM alarm will be set to 60 mg/dL (3.3 mmol/L). When a CGM alarm occurs, the patient will be asked to measure the blood glucose with a BG meter, if he/she is aware of the alarm. The time period for outcome assessment each night will be from the time the system is activated until it is turned off in the morning Pump shut off, when it occurs, will be for up to 2 hours. Multiple instances of pump suspension can occur if there are recurrent predictions of hypoglycemia during the night. Patients will be asked to check blood glucose with the study BG meter, blood ketones with the study ketone meter, and urine ketones with a ketone strip each morning prior to breakfast and enter the results on the study laptop. The patient will be instructed to contact the study physician if the blood glucose or ketone readings are out of an expected range. Patients will be contacted if these morning safety values are not reported as required or are out of range. Patients will be asked to record all overnight carbohydrate intake on the study laptop. Patients will be asked to perform periodic data uploads using the study laptop. Monitoring processes will ensure that the patient is contacted if these uploads do not occur as required, or if review of an upload reveals any extreme, prolonged episodes of low or high blood glucose readings, or elevated morning blood glucose, blood ketone, or urine ketone values. Upon completion of the study, patients as well as study clinicians will be asked to complete a questionnaire regarding use of the study system. There will be one follow-up visit after 21 days in the clinical trial and a second follow-up visit after the completion of 42 nights of successful study system use. A successful night of study system use is defined as use of the system for at least four hours. Phone contacts with the patients will be made once a week.

Official Title
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Reduction of Nocturnal Hypoglycemia by Using Predictive Algorithms and Pump Suspension: An Outpatient Pilot Feasibility and Efficacy Study

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Pump suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least one year and an insulin infusion pump for at least 6 months Age >/= 15.0 - 45 years HbA1c </= 8.0% Availability of internet access for periodic upload of study data Exclusion Criteria: Diabetic ketoacidosis in the past 3 months Hypoglycemic seizure or loss of consciousness in the past 6 months History of seizure disorder (except for hypoglycemic seizure) History of any heart disease including coronary artery disease, heart failure, or arrhythmiasCoronary artery disease or heart failure Cystic fibrosis Current use of oral/inhaled glucocorticoids, beta-blockers or other medications, which in the judgment of the investigator would be a contraindication to participation in the study. History of ongoing renal disease (other than microalbuminuria), or liver disease (Creatinine > 1.5 mg/dL (0.08 mmol/L)) Medical or psychiatric condition that in the judgment of the investigator might interfere with the completion of the protocol such as: Inpatient psychiatric treatment in the past 6 months Uncontrolled adrenal disorder Abuse of alcohol Pregnancy Liver disease as defined by an ALT greater than 3 times the upper limit of normal

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 45 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pump suspension algorithm<br>The study laptop will be running actively during the night and suspending the patient's pump if the algorithm predicts hypoglycemia based on the patient's continuous glucose sensor trend. | Device: Pump suspension<br>* The study laptop will communicate to the pump causing a suspension based on output from the algorithm which predicts hypoglycemia based on the continuous glucose sensor trend.<br>|
| No Intervention: Standard of Care<br>The control algorithm will run passively and not recommend control the patient's pump. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemia Outcome: Percentage of Nights With Sensor Glucose Value </=60 mg/dl | Each night is categorized as to whether hypoglycemia occurred. Hypoglycemia is defined as the occurrence of one or more CGM glucose values ≤60 mg/dL. The percentage of hypoglycemic nights will be tabulated separately with versus without the closed-loop control system in use. A repeated measures logistic regression model will be used to compare intervention versus control nights accounting for correlated data from the same subject and adjusting for the baseline (bedtime) sensor glucose. | Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Sensor Glucose Values 71 to 180 mg/dL | The median percentages of the number of glucose values with values of 71-180 mg/dL overall. | Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use | 
| Percentage of Nights With a Sensor Glucose Value </= 70 mg/dL |  | Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use | 
| Proportion of Nights With a Sensor Glucose Value </= 50 mg/dL |  | Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use | 
| Median Morning Blood Glucose | Measured with a study home blood glucose meter. | 42 mornings following night of system use | 
| Percent of Mornings With Glucose >250 mg/dL | Measured with a study home blood glucose meter. | 42 mornings following night of system use | 
| Percent of Mornings With Blood Ketones >1.0 mmol/L | Blood ketones measured with a study blood ketone meter. | 42 mornings following night of system use | 
| Percent of Mornings With Urine Ketones >/= 15 mg/dl | Urine ketones measured each morning with Ketostix. | 42 mornings following night of system use | 
| Overall Mean Sensor Glucose Overnight | Calculated as the median of the overall mean. | Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use | 
| Overnight Area Under the Curve 250 mg/dl Per 8 Hour | The measure is reporting area under the curve for glucose concentrations below 250 mg/dL and above 60 mg/dL. Overall time below and above a threshold and area under a curve was divided by total time and multiplied by 8 hours. | Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use | 
| Percent of Nights With Sensor Glucose >250 mg/dL |  | Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, Hypoglycemia, Continuous Glucose Monitoring, Pump Suspension