Assessment of an Automatic Closed-loop Insulin Delivery System

Study Overview
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Brief Summary
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The overall aim of this research proposal is to determine the safety, feasibility and efficacy of an automatic closed-loop insulin delivery system.

Detailed Description
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This study will be completed in two parts. The initial part of this study will be an inpatient evaluation of the system with the primary goal of assessing safety and feasibility. This will involve 8 subjects with type 1 diabetes, aged 14 - 40 years, admitted for up to 60 hour. Plasma glucose levels will be collected hourly and tested by YSI (YSI 2300, Yellow Springs Instrument). These studies will be performed at Stanford University and will include group sporting activities to mimic the diabetes camp environment. Capillary blood glucose testing will be performed every 2-3 hours before meals, snacks, exercise, and prebed by subjects with research staff supervision during the day and at 00:00, 03:00 and 07:00 by research staff. These data will be reviewed by the DSMB before proceeding to camp studies. The second part of this study will be to test the efficacy of the system during diabetes summer camps. We will test the system in subjects with type 1 diabetes, aged 14-40 years, attending diabetes camp. There will be 20 subjects recruited, with 10 subjects randomized to the control arm Medtronic 530G system with threshold suspend (control group) and 10 subjects randomized to the automatic closed-loop insulin delivery (intervention group). Capillary blood glucose testing will be performed every 2-3 hours before meals, snacks, exercise and prebed by subjects with research staff supervision and at 00:00, 03:00 and 07:00 by research staff. The primary aim of this study is to generate preliminary data of system safety and efficacy in a closely supervised environment that challenges glucose control.

Official Title
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Assessment of an Automatic Closed-loop Insulin Delivery System

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Device: Automatic closed-loop insulin delivery
* Device: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of type 1 diabetes The diagnosis of type 1 diabetes is based on the investigator's judgment C peptide levels and antibody determinations are not required Daily insulin therapy for ≥ 12 months Insulin pump therapy for ≥ 3 months Age 14.0 - 40.0 years Subject comprehends written English Female subjects who are sexually active must be on acceptable method of contraception e.g. oral contraceptive pill, diaphragm, IUD Female subjects past menarche must have a negative urine pregnancy test Informed consent form is signed by the subject and/or parent and assent assigned by the subject if under 18 years of age For subjects under 18 years, both the subject and parent/guardian understand the study protocol and agree to comply with it. Both parents must sign if possible. Exclusion Criteria: Subject has a medical disorder that in the judgment of the investigator will affect the wearing of the devices or the completion of any aspect of the protocol Diabetic ketoacidosis in the past month Hypoglycemic seizure or loss of consciousness or an event requiring glucagon or IV glucose in the past 3 months Subject has a respiratory condition such as asthma, treated with systemic or inhaled corticosteroids in the previous 6 months or cystic fibrosis Subject has a history of any cardiac or vascular disorder such as myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack, cerebrovascular accident, angina, congestive heart failure, arrhythmia or thromboembolic disease Subject has a history of liver or kidney disease (other than microalbuminuria) Subject has active Graves' disease Subjects with inadequately treated thyroid disease or celiac disease Subject has a neurologic disorder that in the judgment of the investigator will affect completion of the protocol Subject has a history of diagnosed medical eating disorder Subject has a history of known illicit drug abuse Subject has a history of known prescription drug abuse Subject has a history of current alcohol abuse Subject has a history of visual impairment which would not allow subject to participate Subject has an active skin condition that would affect sensor placement Subject has adhesive allergies Subjects requiring an intermediate or long-acting insulin (such as NPH, detemir or glargine) Subjects requiring other anti-diabetic medications other than insulin (oral or injectable) Current use of oral/inhaled glucocorticoids or other medications, which in the judgment of the investigator would be a contraindication to participation in the study Subject is currently on beta blocker medication Subject is currently participating in another investigational study (drug or device) Subject is deemed by the investigator to be unwilling or unable to follow the protocol Presence of a febrile illness within 24 hours of enrollment

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 40 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: automatic closed-loop insulin delivery<br>The closed-loop arm will consist of participants wearing a sensor and transmitter which transmits sensor glucose data. The algorithm determines insulin delivery rates and this is delivered in microboluses every 5 minutes | Device: Automatic closed-loop insulin delivery<br>* Sensor transmit glucose data every 5 minutes to the control algorithm which adjusts insulin delivery every 5 minutes.<br>|
| Active Comparator: Control<br>The subjects in the control arm will wear the 530G system using Enlite and MiniLink transmitter and threshold suspend. | Device: Control<br>* Threshold suspend<br>* Other names: 530G Pump;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Automatic Closed Loop Insulin Delivery System in Adolescents and Adults With Type 1 Diabetes | As measured by the number of events of plasma glucose values ≤ 50 mg/dL OR frequency of system alerts preceding a plasma glucose value of ≤ 50 mg/dL in all subjects As measured by the number of events of system alerts of plasma glucose values >300 mg/dL lasting for more than one hour in all subjects. As measured by number of events of serum ketones >3 mmol/L in all subjects As measured by the number of events meeting the criteria for severe hypoglycemia, defined as hypoglycemic seizure, loss of consciousness or coma or an event requiring administration of glucagon or IV glucose in all subjects | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Using the Automatic Closed Loop Delivery System in Adolescents and Adults With Type 1 Diabetes | As measured by the system initiating and operating properly for at least 75% of the time for 75% of subjects. As measure by the completion of study enrollment procedures and education on system use within 2 hours for 75% of the subjects. | 6 days | 
| Efficacy of Hybrid Closed-loop System in Comparison With Control | As measured by overall mean sensor glucose percent time in range 70-180 mg/dL. | 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin Infusion Systems, Continuous Glucose Monitors