Early Feasibility Study 2 of Outpatient Control-to-Range - Testing System Efficacy

The overall objective of this project is to sequentially test, validate, obtain regulatory
approval for, and deploy at home, a closed-loop Control-to-Range (CTR) system for optimal
blood glucose (BG) regulation in people with type 1 diabetes. The CTR system is comprised of
two algorithmic layers: a Safety Supervision Module (SSM) and Insulin on Board Tracking and
Safety Module (ITSM), and an automated Range Correction Module (RCM). Both modules will
receive continuous glucose monitoring (CGM) and insulin delivery data. The SSM and ITSM will
monitor the safety of the subject's continuous subcutaneous insulin infusion pump (CSII) to
prevent hypoglycemia. The RCM will be responsible for optimizing BG control and mitigating
postprandial hyperglycemic excursions through series of insulin boluses. To run CTR, we will
use our wearable artificial pancreas platform, known as DiAs (Diabetes Assistant), which
consists of a smart phone running CTR and connected to standard insulin delivery and CGM
devices.

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.