Early Feasibility Study of Adaptive Advisory/Automated (AAA) Control of Type 1 Diabetes
Early Feasibility Study of Adaptive Advisory/Automated (AAA) Control of Type 1 Diabetes
The purpose of this study is to use an Advisory/Automated Adaptive (AAA) Control system for
 insulin delivery in adults with Type 1 Diabetes (T1DM) in an outpatient setting to evaluate
 the system's ability to significantly improve blood glucose levels. One component of this
 study is evaluating if the AAA Control system run on the Diabetes Assistant (DiAs) system can
 prevent hypoglycemia during and following exercise more efficiently during a 40 hour trial.
 Another component of this study is evaluating AAA Control overnight only in 5 consecutive
 overnights. This protocol represents a culmination of prior clinical trials in development of
 this AAA system and benefits from the synthesis of those components.
The primary goal of this study is to test an Advisory/Automated Adaptive (AAA) Control
 system, which includes three interacting control modules:

 -  Module 1 - Automated Safety Supervision (SSM) responsible for prevention of
 hypoglycemia, which can be adapted (individualized) with prior data for each subject;

 -  Module 2 - Advisory Module (AM) responsible for pre-meal boluses and postprandial
 corrections, which can be adapted (individualized) with prior data for each subject;

 -  Module 3 -- Automated Basal Rate Module (BRM) responsible for augmentation of basal rate
 to compensate for changes in insulin sensitivity, particularly overnight (e.g. dawn
 phenomenon), which can be adapted with prior data for each subject.

 Daytime control (40hour studies) includes all 3 modules (n=36). Overnight only closed loop
 control (5 consecutive overnights) includes Module 1 and 3 (n=5-7).
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 glucose ≥200 mg/dL -
 confirmed iii. Hemoglobin A1C (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 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 24 hours prior
 to and during CGM use.

 9. Ability to access the Internet and upload CGM data via the company software during the
 data collection period.

 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. 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,
 uncontrolled 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 Continuous Glucose Monitor (CGM) (implantable
 cardioverter-defibrillator, electronic pacemaker, neurostimulator, intrathecal pump,
 and cochlear implants).

 8. Anticoagulant therapy other than aspirin.

 9. Oral steroids.

 10. Subjects currently taking Amylin.

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

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

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

 14. Known current or recent alcohol or drug abuse.

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

 16. 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, and
 cellulitis).

 17. In adherence with the One Touch Ultra 2 User Guide that may be used in the
 experimental session and overnight during substudy, subjects with hematocrit levels
 less than 30% and above 55% will be excluded.

 18. Impaired hepatic function measured as alanine aminotransferase or aspartate
 aminotransferase

 ≥three times the upper reference limit.

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

 20. 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.

 21. Active gastroparesis requiring current medical therapy.

 22. 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.

 23. Uncontrolled thyroid disease.

 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. Active enrollment in another treatment clinical trial. Observational trials may be
 permitted at the discretion of the study physician.

 27. Use of anti-diabetic agents other than continuous subcutaneous insulin infusion (CSII)
 including long-acting insulin, intermediate-acting insulin, metformin, sulfonylureas,
 meglitinides, thiazolidinediones, Dipeptidyl peptidase-4 inhibitors, glucagon- like
 peptide 1 agonists, and alpha-glucosidase inhibitors

 28. Unwillingness to use an approved form of birth control during this study by a sexually
 active female participant.

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

 RESTRICTIONS ON USE OF OTHER DRUGS OR TREATMENTS

 1. Use of anti-diabetic agents other than CSII including long-acting insulin,
 intermediate-acting insulin, metformin, sulfonylureas, meglitinides,
 thiazolidinediones, Dipeptidyl peptidase-4 inhibitors, glucagon- like peptide 1
 agonists, and alpha-glucosidase inhibitors.

 2. Acetaminophen will be restricted starting 24 hours prior to CGM use.

 3. Medications that block symptoms of hypoglycemia, including but not limited to beta
 blockers.