Effect of Closed Loop Glucose Control on Exercise-Associated Hypoglycemia

This is an open-label, single-center, randomized crossover study evaluating the performance
of a closed-loop insulin delivery system using a subcutaneous glucose sensor and an external
insulin pump and comparing it to an open-loop delivery system during aerobic exercise.
Subject participation will be for a maximum of 16 weeks including an outpatient study (up to
6 days) and two inpatient studies (one closed-loop; the other open-loop). The closed- and
open-loop visit consists of approximately 67 hours over 4 days and 3 nights.

Inclusion Criteria:

- Male and female subjects between 12-30 years of age.

- Subjects must weigh at least 50 kg to accommodate phlebotomy.

- Previously diagnosed Type 1 Diabetes Mellitus

- Diabetes duration at least 1 year.

- Currently treating their diabetes with an insulin pump.

- A1C of ≤ 9.0 % at time of enrollment.

- Willing to have an intravenous (IV) line inserted for frequent blood sampling and
infusion of glucose if needed.

- Willing to wear two (2) subcutaneous glucose sensors and two (2) transmitters
simultaneously during closed-loop portion of the study.

- Be in good general health without other acute or chronic illnesses except treated
hypothyroidism or celiac disease and asthma not requiring glucocorticoid use.

- Able to tolerate a 75-minute exercise period of moderate intensity.

- Speak and understand English.

- Subject and parent (if minor) must be able to comprehend and sign the informed consent
form and other study documents.

Exclusion Criteria:

- Pregnancy (urine pregnancy test) or lactation, if female.

- Subject has any major concomitant disease or any physical or psychological disorder
within the last five years, which might be considered life threatening, or which might
confound the collection or interpretation of the study data.

- Subject has a cardiac pacemaker or similar device that may be sensitive to radio
frequency telemetry.

- Subject using any of the following medications:

- glucocorticoids

- cyclosporine

- L-asparaginase

- niacin

- protease inhibitors

- anti-psychotics

- GnRH agonists

- beta-blockers

- calcium channel blockers

- immunosuppressants

- over-the-counter medications that may effect glucose metabolism.

- Subject has any of the following conditions

- insulin allergy

- severe insulin resistance

- exercise-induced asthma

- musculoskeletal problems that may impact ability to complete exercise protocol

- substance abuse

- skin ulcers or poor wound healing

- bleeding disorders

- chronic infections

- eating disorders

- give a history of or are predisposed to major stress

- any other major organ system disease.

- Subject has experienced two (2) or more severe hypoglycemic events -seizures/coma
requiring assistance in the past six (6) months.

- Subject has any other condition that in the investigator's opinion warrants exclusion
from the study or precludes him/her from completing the protocol.

- Subjects using dietary supplements within 14 days of study enrollment

- Subject is currently enrolled in another study.