Closed Loop Control in Adolescents Using Heart Rate as Exercise Indicator

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.

Inclusion Criteria:

1. 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

2. 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

3. 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.