Closed Loop Control in Adolescents Using Heart Rate as Exercise Indicator

Study Overview
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Brief Summary
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The purpose of this study is to see if the Artificial Pancreas (AP) Platform can successfully control blood sugar in people with type 1 diabetes mellitus on insulin pump therapy in a hospital setting. Investigators will also be studying to see if the heart rate informed Control To Range (hrCTR) can improve the performance of the system during and immediately after exercise.

Detailed Description
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The artificial pancreas (AP), known as Closed-Loop Control of blood glucose in diabetes, is a system combining a continuous glucose monitor (glucose sensor), a control algorithm (complex mathematical formulas), and an insulin pump. The algorithms are intended to maintain your blood glucose level within a certain range. This is called Control-to-Range. The algorithms are intended to maintain your blood glucose level within a certain range. The algorithms run on a portable AP platform on an Android smart phone, called the Diabetes Assistant (DiAs) Medical Platform. In this study, researchers hypothesize that the heart rate informed Control To Range (hrCTR) will limit the risk for hypo and hyperglycemia during and immediately after exercise in adolescents 12 - 17 years of age and assess if the hrCTR will improve additional measures of overall short term glycemic control in this population. This trial will be performed at both Virginia Commonwealth University and the University of Virginia. IRB approvals have been obtained at both institutions.

Official Title
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Closed Loop Control in Adolescents Using Heart Rate as Exercise Indicator

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Device: heart rate Control to Range System (hrCTR) using DiAs Platform
* Other: DiAs Control-to-Range System not informed for heart rate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Criteria for documented hyperglycemia (at least 1 must be met): Fasting glucose ≥ 126 mg/dL - confirmed Two-hour Oral Glucose Tolerance Test (OGTT) glucose ≥ 200 mg/dL - confirmed Hemoglobin A1c (HbA1c) ≥ 6.5% documented - confirmed Random glucose ≥ 200 mg/dL with symptoms No data are available from the time of diagnosis but the participant has a convincing history of medical care and biochemical parameters consistent with T1DM Criteria for requiring insulin at diagnosis (1 must be met): Participant required insulin at diagnosis and continually thereafter Participant did not start insulin at diagnosis but upon investigator review likely needed insulin (significant hyperglycemia that did not respond to oral agents) and did eventually require insulin that has been used continually Criteria for Type 1 Diabetes Mellitus (T1DM) (at least 1 must be met): Documented low or absent C-peptide level. Documented presence of islet cell autoantibodies (ICA) or glutamic acid decarboxylase (GAD65) autoantibodies. No data are available from the time of diagnosis but the participant has a convincing history of medical care and biochemical parameters consistent with T1DM In addition, all subjects will meet the following additional criteria: Use an insulin pump (CSII) to treat his/her diabetes for at least 6 months Actively use a bolus calculator with the current insulin pump with pre-defined parameters for carbohydrate (CHO) ratio, insulin sensitivity factor (ISF), and target glucose Current HbA1c between 5.0% and 10.5% as measured with DCA2000 or equivalent device Not currently known to be pregnant, breast feeding, or intending to become pregnant (females) Demonstration of proper mental status and cognition for the study Willingness to avoid consumption of acetaminophen-containing products while wearing the continuous glucose monitor sensor. Exclusion Criteria: Clinical diagnosis of Type 2 Diabetes Mellitus (T2DM) Diabetic ketoacidosis within 6 months prior to enrollment Severe hypoglycemia resulting in seizure or loss of consciousness within 3 months prior to enrollment Pregnancy, breast feeding, or intention to become pregnant Subjects weighing less than 40 kg Hematocrit <36% (females); <38% (males) Conditions which may increase the risk of hypoglycemia such as known history of cerebrovascular event, history of arrhythmias, seizure disorder, syncope, adrenal insufficiency, or neurologic disease Additional conditions which may inhibit the ability to perform exercise (e.g. injury to or immobility of limbs, neuromuscular disease, exercise-induced asthma requiring inhaler use within the last 12 months or clinically impaired pulmonary function) 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) 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 continuous glucose monitor (implantable cardioverter defibrillator, electronic pacemaker, neurostimulator, intrathecal pump, and cochlear implants) Medical condition requiring use of an acetaminophen-containing medication that cannot be withheld for the study admission. Psychiatric disorders that would interfere with study tasks (e.g. inpatient psychiatric treatment within 6 months prior to enrollment, uncontrolled anxiety or panic disorder) Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation Medical conditions that would make operating a continuous glucose monitor, cell phone or insulin pump difficult (e.g. blindness, severe arthritis, immobility) Any skin condition that prevents sensor or pump placement on the abdomen or arm (e.g. bad sunburn, pre-existing dermatitis, intertrigo, psoriasis, extensive scarring, cellulitis) Known micro vascular (diabetic) complications (other than diabetic non-proliferative retinopathy), such as history of laser coagulation, proliferative diabetic retinopathy, known diabetic nephropathy (other than microalbuminuria with normal creatinine) or neuropathy requiring treatment Active gastroparesis requiring current medical therapy If on antihypertensive, thyroid, or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study Known bleeding diathesis or dyscrasia Allergy to medical adhesives, components of the insulin pump insertion set or continuous glucose monitor sensor Anticoagulant therapy other than aspirin Oral steroids Active enrollment in another clinical trial Unwillingness to avoid acetaminophen while wearing the continuous glucose monitor sensor. Unwillingness to withhold dietary supplements two weeks prior to and during admission Unwillingness to use an approved form of birth control during this study by a sexually active female participant. Subject develops a febrile illness within 24 hours of inpatient admission.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: heart rate Control to Range System (hrCTR) THEN No heart rate Control to Range System (hrCTR)<br>The Diabetes Assistant (DiAs) Control-to-Range system is notified of heart rate during exercise. The study team member will activate and deactivate a heart rate button when the subject's heart rate exceeds and then returns below 140 beats per minute. | Device: heart rate Control to Range System (hrCTR) using DiAs Platform<br>* Diabetes Assistant (DiAs) Medical Platform System A smart-phone medical platform (DiAs); Continuous Glucose Monitor; Insulin pump; Bluetooth connection; Remote Monitoring Server.<br>|
| Placebo Comparator: No heart rate Control to Range System (hrCTR) THEN heart rate Control to Range System (hrCTR)<br>Using the DiAs Platform, the Control-to-Range system is not notified of the heart rate during exercise. Heart rate not of interest in this arm. | Device: heart rate Control to Range System (hrCTR) using DiAs Platform<br>* Diabetes Assistant (DiAs) Medical Platform System A smart-phone medical platform (DiAs); Continuous Glucose Monitor; Insulin pump; Bluetooth connection; Remote Monitoring Server.<br>Other: DiAs Control-to-Range System not informed for heart rate<br>* Not informing system of heart rate during exercise.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low Blood Glucose Index (LBGI) | The Low Blood Glucose Index, which quantifies the risk for hypoglycemia, and the hypoglycemic count (number sequences of blood glucose less than 70 mg/dL). The LBGI is a metric of the frequency and severity of hypoglycemia, based on an increasing weighting of progressively low glucose readings. The LBGI is measured on a scale from 0 to 100 and a higher score indicates a worse outcome. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artificial Pancreas Project, Diabetes Assistant (DiAs) Medical Platform System, Artificial Pancreas Platform, Insulin Pump, Continuous Glucose Monitor, Closed-Loop Control, heart rate Control to Range System (hrCTR)