Feasibility Study of a Modular Control to Range System in Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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In this protocol the investigators plan to demonstrate the feasibility of a modular insulin management system based on continuous glucose monitoring and targeted towards the avoidance of hypoglycemic and prolonged hyperglycemic episodes (i.e. control to range). The protocol is designed to challenge the insulin management system with meals and mild exercise, so as to demonstrate its capacity to avoid large glucose excursion with changing metabolic state. This system is designed to both monitor the meal boluses of the patient and correct it in case of observed/predicted under insulinization (avoidance of prolonged hyperglycemia), based on a coarse and subjective knowledge of the meal amount, a precise understanding of the subject's day to day insulin treatment, continuous glucose monitoring, and past insulin injections; predict and avoid hypoglycemic events, based on continuous glucose reading and past insulin injection. The investigators plan to enroll 12 adult Type 1 Diabetes Mellitus (T1DM) patients (expected retention 10/12) and compare glucose control performances under two treatments: standard vs. the new insulin management system. The protocol will include a total of 6 admissions per subject (4 out-patients and 2 in-patients): screening, effort test, CGM insertion 1, inpatient 1, CGM insertion 2, and inpatient 2. During the 24h inpatient admissions, the patients will be challenged with 30 minutes of mild exercise and 3 meals, insulin coverage of these events will vary depending on the chosen treatment, each subject will be exposed to both studied treatments (repeated measure design).The order of treatment during the inpatient admissions will be randomized.

Official Title
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Feasibility Study of a Modular Control to Range System in T1DM

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Device: Closed Loop Control (CLC)
* Device: Open Loop


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 21 years of age and up to and including 65 years of age. Have Type 1 Diabetes Mellitus as defined by American Diabetes Association criteria or judgment of physician for at least 2 years (including those who may also be treated with metformin, thiazolidinedione, exenatide, or pramlintide). Use of an insulin pump If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, have stability on the medication for at least 2 months prior to enrollment in the study Willingness to use lispro (Humalog) insulin for the duration of the inpatient study Demonstration of proper mental status and cognition for the study Willingness to stop using any dietary supplements for two weeks prior to admission and for the duration of their participation. Exclusion Criteria: Age <21or >65 Pregnancy Hematocrit <36% (females); <38% (males) HemoglobinA1c > 10.0 Symptomatic coronary artery disease (e.g. history of myocardial infarction, history of acute coronary syndrome, history of therapeutic coronary intervention, history of coronary bypass or stenting procedure, stable or unstable angina, episode of chest pain of cardiac etiology with documented EKG changes, positive stress test or catheterization with coronary blockages >50%). Use of a medication that significantly lowers heart rate (beta blockers, reserpine, guanethidine, methyldopa, clonidine, cimetidine, digitalis, calcium channel blockers, amiodarone, antiarrythmic drugs, or lithium) Congestive heart failure History of a cerebrovascular event Use of a medication that significantly impacts glucose metabolism (oral steroids) Atrial fibrillation Uncontrolled hypertension (resting blood pressure >140/90) History of a systemic or deep tissue infection with methicillin- resistant staph aureus or Candida albicans Use of a device that may pose electromagnetic compatibility issues and/or radiofrequency interference with the FreeStyle NavigatorTM CGM (implantable cardioverter-defibrillator, electronic pacemaker, neurostimulator,intrathecal pump, and cochlear implants) Active enrollment in another clinical trial Allergy or adverse reaction to lispro insulin Known adrenal gland problem, pancreatic tumor, or insulinoma Current alcohol abuse by patient history, substance abuse by patient history, or severe mental illness Retinopathy and renal failure Uncontrolled anxiety or panic disorder Known bleeding diathesis or dyscrasia Renal insufficiency (creatinine >1.5) Any comorbid condition affecting glucose metabolism

Ages Eligible for Study
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Minimum Age: 21 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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Closed Loop Control (CLC)<br>The CLC used a computer to make recommendations for their insulin treatment. This study arm was designed to demonstrate management of glucose using a modular insulin management system based on continuous glucose monitoring and targeted towards the avoidance of hypoglycemic and prolonged hyperglycemic episodes (i.e. control to range). This system was designed to both: monitor the meal boluses of the patient and correct it in case of observed/predicted under insulinization (avoidance of prolonged hyperglycemia), based on a coarse and subjective knowledge of the meal amount, a precise understanding of the subject's day to day insulin treatment, continuous glucose monitoring, and past insulin injections; predict and avoid hypoglycemic events, based on continuous glucose reading and past insulin injection. | Device: Closed Loop Control (CLC)<br>* In this study, the researchers compared the management of diabetes during physical activity and meals with the closed-loop system developed at the University of Virginia. This Control to Range System uses two DexCom Seven Continuous Glucose Monitor, a computer containing an investigational control algorithm (well-defined instructions that are expressed in mathematical equations), and an OmniPod Insulin Management System, a portable subcutaneous (under the skin) insulin pump. During the closed-loop admission, the computer used CGM values to make recommendations of insulin treatment based on the algorithms.<br>|
| Placebo Comparator: Open Loop<br>The subject were in charge of their insulin treatment. | Device: Open Loop<br>* This admission was to assess the subjects' level of glucose control and created a base to compare the performance of the closed-loop system. Subjects monitored their own blood glucose values and administer their basal/bolus as they would at home. Subjects use their own pump. Otherwise, the admission remained the same as in the closed-loop admission (i.e. meals, exercise, etc...).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemic Events | Number of hypoglycemic events below 70 mg/dL per patient per day | Throughout each 22-hour closed-loop and open-loop admission for sCTR and eCTR | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Time Spent in Near Normoglycemia | Comparison of time spent in near normoglycemia (3.9 to 10 mmol/mL) in open-loop vs closed-loop sCTR and eCTR. | Throughout each 22-hour closed-loop and open-loop admission for sCTR and eCTR | 
| Mean Glucose | Average plasma glucose concentration in mg/dl | Throughout each 22-hour closed-loop and open-loop admission for sCTR and eCTR |