Early Feasibility Study 2 of Outpatient Control-to-Range - Testing System Efficacy (Italy)
Early Feasibility Study 2 of Outpatient Control-to-Range - Testing System Efficacy (Italy)
An unblinded, randomized, cross-over design with each patient participating in two 40-hour
 outpatient admissions: (a) Experimental involving automated Control to Range (CTR) and (b)
 Control using Continuous Glucose Monitor (CGM)- augmented insulin pump treatment outside of a
 hospital based clinical research center.
The principal goal is to validate a smart phone-based control-to-range (CTR) system for
 ambulatory use and to estimate the effect of CTR vs. sensor-augmented pump therapy, thereby
 providing justification for further larger home-based trials of CTR.
Inclusion Criteria:

 1. ≥21 and <65 years old.

 2. Clinical diagnosis of type 1 diabetes mellitus. For an individual to be enrolled at
 least one criterion from each list must be met.

 o Criteria for documented hyperglycemia (at least 1 must be met): i. Fasting glucose
 ≥126 mg/dL - confirmed ii. Two-hour Oral Glucose Tolerance Test (OGTT) glucose ≥200
 mg/dL - confirmed iii. HbA1c ≥6.5% documented - confirmed iv. Random glucose ≥200
 mg/dL with symptoms v. No data at diagnosis is available but the participant has a
 convincing history of hyperglycemia consistent with diabetes

 o Criteria for requiring insulin at diagnosis (1 must be met): i. Participant required
 insulin at diagnosis and continually thereafter ii. 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 iii. Participant did not start insulin at diagnosis but continued
 to be hyperglycemic, had positive islet cell antibodies - consistent with latent
 autoimmune diabetes in adults (LADA) and did require insulin eventually and used
 continually

 3. Use of an insulin pump to treat his/her diabetes for at least 1 year.

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

 5. HbA1c <9% as measured with DCA2000 or equivalent device.

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

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

 8. Willingness to avoid consumption of acetaminophen-containing products during the study
 interventions involving CGM use.

 9. 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. Severe hypoglycemia resulting in seizure, loss of consciousness, or diabetic
 ketoacidosis within the 12 months prior to enrollment.

 2. Pregnancy; breast feeding, or intention of becoming pregnant.

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

 4. Conditions which may increase the risks associated with possible hypoglycemia, such as
 any active cardiac disorder/arrhythmia, uncontrolled coronary artery disease during
 the previous year (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.

 5. Self-reported hypoglycemia unawareness.

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

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

 8. Anticoagulant therapy other than aspirin.

 9. Oral steroids.

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

 11. Psychiatric disorders that would interfere with study tasks (e.g. inpatient
 psychiatric treatment within 6 months prior to enrollment).

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

 13. Known current or recent alcohol or drug abuse.

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

 15. 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).

 16. In adherence with the One Touch Ultra 2 User Guide, subjects with hematocrit levels
 less than 30% and above 55% will be excluded.

 17. Impaired hepatic function measured as alanine aminotransferase or aspartate
 aminotransferase ≥three times the upper reference limit.

 18. Impaired renal function measured as creatinine >1.2 times above the upper limit of
 normal.

 19. Uncontrolled microvascular (diabetic) complications, such as current proliferative
 diabetic retinopathy or macular edema, known diabetic nephropathy (other than
 microalbuminuria with normal creatinine) or neuropathy requiring treatment.

 20. Active gastroparesis requiring current medical therapy.

 21. 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.

 22. Uncontrolled thyroid disease.

 23. Known bleeding diathesis or dyscrasia.

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

 25. Active enrollment in another clinical trial.

 26. Use of anti-diabetic agents other than continuous subcutaneous insulin infusion (CSII)
 including long-acting insulin, intermediate-acting insulin, metformin, sulfonylureas,
 meglitinides, thiazolidinediones, DPP-IV inhibitors, glucagon-like peptide 1 agonists,
 and alpha-glucosidase inhibitors

 27. Subjects with basal rates less than 0.01U/hr.