Feasibility Study of Closed Loop Control in Type 1 Diabetes Using Heart Rate Monitoring as an Exercise Marker
Feasibility Study of Closed Loop Control in Type 1 Diabetes Using Heart Rate Monitoring as an Exercise Marker
The purpose of this study is to see if the Artificial Pancreas Platform (AP Platform = Cell
 Phone + Closed Loop Control) 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 information about heart rate can help the AP Platform reduce hypoglycemia
 related to exercise.
The combination of the Control to Range system and the cell phone is called the "Artificial
 Pancreas (AP) Platform". The purpose of this study is to see if this investigational
 technology can help control blood sugar in people with type 1 diabetes mellitus on insulin
 pump therapy can be successfully used and supervised in a hospital setting. This study is
 also being done to see if giving information about heart rate to the Closed-to-Range System
 can reduce hypoglycemia as it relates to exercise. Subjects will exercise on an exercise bike
 in the clinical research unit. During one exercise testing session, the Closed-to-Range
 System will receive information about your heart rate (Experimental Condition). During the
 other exercise testing session, the Control to Range System will not receive information
 about your heart rate (Control Condition). This part of the study is being done to see
 whether heart rate information helps the Closed-to-Range System reduce the occurrences of
 exercise-related hypoglycemia.

 The Closed-to-Range system has two parts (modules) that can work together or separately.

 A. The Safety Supervision Module (SSM) helps to prevent low blood sugars. It can reduce the
 amount of basal insulin that the pump is delivering and alert you if carbohydrates are needed
 to help prevent a low blood sugar. This module will be active at all times during the
 operation of the Closed-to-Range System.

 B. The Hyperglycemia Mitigation Module (HMM) helps to prevent high blood sugars. It can
 instruct the insulin pump to deliver small boluses to help prevent high blood sugar. It can
 also help warn you of a possible pump problem if the blood sugar level is not responding to
 the insulin as it should.

 The Closed-to-Range System works with the insulin pump and continuous glucose monitor to help
 keep the blood sugar in a desired range (80-180 mg/dL) during the day and help avoid
 hypoglycemia during the night.
Inclusion Criteria

 1. ≥21 and <65 years old with clinical diagnosis of Type 1 Diabetes Mellitus for at least
 1 year.

 2. Criteria for documented hyperglycemia (at least 1 criterion must be met):

 1. Fasting glucose ≥126 mg/dL - confirmed

 2. Two-hour Oral Glucose Tolerance Test (OGTT) glucose ≥200 mg/dL - confirmed

 3. HbA1c ≥6.5% documented - confirmed

 4. Random glucose ≥200 mg/dL with symptoms

 3. No data at diagnosis is available but the participant has a convincing history of
 hyperglycemia consistent with diabetes.

 Criteria for requiring insulin at diagnosis (at least 1 criterion must be met):

 1. Participant required insulin at diagnosis and continually thereafter

 2. 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 require insulin eventually and used continually

 3. Participant did not start insulin at diagnosis but continued to be hyperglycemic,
 had positive islet cell antibodies - consistent with latent autoimmune diabetes
 (LADA) in adults and did require insulin eventually and used continually.

 Criteria for Type 1 Diabetes Mellitus (at least 1 criterion must be met)

 4. Documented low or absent C-peptide level.

 5. Documented presence of Islet Cell Cytoplasmic Autoantibodies (ICA) or Glutamic
 Acid Decarboxylase (GAD65) antibodies.

 4. Use of an insulin pump to treat his/her diabetes for at least 6 months

 5. Actively using a bolus calculator with the current insulin pump with pre-defined
 parameters for carbohydrate (CHO) ratio, insulin sensitivity factor (ISF), and target
 glucose

 6. HbA1c between 5.0% and 10.5% as measured with DCA2000 or equivalent device

 7. Not currently known to be pregnant, breast feeding, or intending to become pregnant
 (females)

 8. Demonstration of proper mental status and cognition for the study.

 9. Willingness to avoid consumption of acetaminophen-containing products during the study
 interventions involving continuous glucose monitor use.

 10. 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.

 Exclusion Criteria

 1. Clinical diagnosis of Type 2 Diabetes Mellitus

 2. Diabetic ketoacidosis within the 6 months prior to enrollment

 3. Severe hypoglycemia resulting in seizure or loss of consciousness in the 3 months
 prior to enrollment

 4. Pregnancy, breast feeding, or intention of becoming pregnant

 5. Uncontrolled arterial hypertension (diastolic blood pressure >90 mmHg and/or systolic
 blood pressure >160 mmHg)

 6. Hematocrit <36% (females); <38% (males)

 7. Uncontrolled thyroid disease or thyroid replacement as determined by a
 thyroid-stimulating hormone (TSH) out of the UVa reference range.

 8. Impaired hepatic function measured as alanine aminotransferase or aspartate
 aminotransferase >2 times the upper limit of normal

 9. Impaired renal function measured as creatinine >1.5 mg/dL

 10. Conditions which may increase the risk of hypoglycemia such as known coronary artery
 disease (e.g. history of myocardial infarction, acute coronary syndrome, therapeutic
 coronary intervention, coronary bypass or stenting procedure, stable or unstable
 angina, episode of chest pain of cardiac etiology with documented EKG changes, or
 positive stress test or catheterization with coronary blockages >50%), congestive
 heart failure, history of cerebrovascular event, seizure disorder, syncope, adrenal
 insufficiency, neurologic disease or atrial fibrillation

 11. Additional conditions which may inhibit the ability to perform exercise on a
 stationary bike (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)

 12. 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)

 13. History of a systemic or deep tissue infection with methicillin-resistant staph aureus
 or Candida albicans

 14. Use of a device that may pose electromagnetic compatibility issues and/or
 radiofrequency interference with the continuous glucose monitor (CGM) (implantable
 cardioverter-defibrillator, electronic pacemaker, neurostimulator, intrathecal pump,
 and cochlear implants)

 15. Medical condition requiring use of an acetaminophen-containing medication that cannot
 be withheld for the study admissions.

 16. Psychiatric disorders that would interfere with study tasks (e.g. inpatient
 psychiatric treatment within 6 months prior to enrollment, uncontrolled anxiety or
 panic disorder)

 17. Mental incapacity, unwillingness or language barriers precluding adequate
 understanding or cooperation

 18. Current or recent alcohol or drug abuse by patient history

 19. Medical conditions that would make operating a CGM, cell phone or insulin pump
 difficult (e.g. blindness, severe arthritis, immobility)

 20. 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)

 21. Known microvascular (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

 22. Active gastroparesis requiring current medical therapy

 23. If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of
 stability on the medication for the past 2 months prior to enrollment in the study

 24. Known bleeding diathesis or dyscrasia

 25. Known allergy to medical adhesives, components of the insulin pump insertion set or
 continuous glucose monitor sensor

 26. Anticoagulant therapy other than aspirin

 27. Oral steroids

 28. Active enrollment in another clinical trial

 29. Unwillingness to avoid acetaminophen while the continuous glucose monitor is in use.

 30. Unwillingness to withhold dietary supplements two weeks prior to admission and for the
 duration of the study participation.

 31. Subjects with basal rates less than 0.05.

 Restrictions on use of other drugs or treatments

 1. Pramlintide, liraglutide and exenatide will be held for the duration of the study
 intervention.

 2. Oral steroids are excluded

 3. Anticoagulant therapy other than aspirin is excluded

 4. Acetaminophen will not be allowed while the continuous glucose monitor is in use

 5. Dietary supplements will be withheld two weeks prior to admission and for the duration
 of study participation

 6. Beta blockers, reserpine, guanethidine, methyldopa, clonidine, cimetidine, digitalis,
 calcium channel blockers, amiodarone, antiarrythmic drugs, and lithium are excluded