Single Hormone Closed Loop Study With PDT Sensor

Subjects will undergo one 12 hour inpatient study. During this intervention visit, subjects
will wear the single hormone closed loop system which includes two t:slim insulin pumps to
deliver insulin or saline through two investigational PDT glucose sensing cannulas, and a
Dexcom G5 CGM to measure glucose. The subject will come to the research center at
approximately 7am for the inpatient visit. The Dexcom G5 sensor and PDT glucose sensing
cannulas will be placed after arrival. An 18-22 gauge IV catheter will be placed for blood
sampling every 15 minutes after sensor warm-up is complete for measuring blood glucose
concentration. After a 2 hour warm-up period for the G5 sensor, glucose will be controlled
using the FMPD single hormone mode. The single hormone mode of the controller determines
insulin delivery rates based on proportional and derivative error through one t:slim insulin
pump. The second t:slim insulin pump will deliver normal saline at the same delivery rates as
the insulin. Subjects will eat breakfast and lunch at approximately 11 am and 3 pm
respectively. Subjects will have the ability to complete light exercise on a treadmill. The
closed loop system will be stopped at approximately 6pm with removal of all devices.

During the study, the subject will wear one subcutaneous DexcomTM G5 continuous glucose
monitoring (CGM) system. The CGM system will provide sensed glucose data every 5 minutes. The
accuracy of the sensed data will be obtained by reference measurements of two YSI venous
blood glucose values to calibrate the sensor at the beginning of the closed loop study.
Sensed glucose data will be wirelessly transmitted via Bluetooth Low Energy (BTLE) from the
Dexcom G5 transmitter to the Nexus 5 master controller every five minutes. The controller is
a Google Nexus 5 phone. The smart phone will wirelessly communicate via BTLE to two Tandem
t:slim insulin pumps, one for automated insulin delivery and one of automated saline
delivery.

Inclusion Criteria:

- Diagnosis of type 1 diabetes mellitus for at least 1 year.

- Male or female subjects 21 to 65 years of age.

- Current use of an insulin pump for at least 3 months with stable insulin pump settings
for > 2 weeks.

- HbA1c ≤ 10% at screening.

- Body Mass Index ≥ 22.

- Total daily insulin requirement is less than 200 units/day.

- Willingness to follow all study procedures, including attending all clinic visits.

- Willingness to sign informed consent and HIPAA documents.

Exclusion Criteria:

- Female of childbearing potential who is pregnant or intending to become pregnant or
breast-feeding, or is not using adequate contraceptive methods. Acceptable
contraception includes birth control pill / patch / vaginal ring, Depo-Provera,
Norplant, an IUD, the double barrier method (the woman uses a diaphragm and spermicide
and the man uses a condom), or abstinence.

- Any cardiovascular disease, defined as a clinically significant EKG abnormality at the
time of screening or any history of: stroke, heart failure, myocardial infarction,
angina pectoris, or coronary arterial bypass graft or angioplasty. Diagnosis of 2nd or
3rd degree heart block or any non-physiological arrhythmia judged by the investigator
to be exclusionary.

- Renal insufficiency (GFR < 60 ml/min, using the MDRD equation as reported by the OHSU
laboratory).

- Liver failure, cirrhosis, or any other liver disease that compromises liver function
as determined by the investigator.

- Hematocrit of less than 36% for men, less than 32% for women.

- History of severe hypoglycemia during the past 12 months prior to screening visit or
hypoglycemia unawareness as judged by the investigator.

- History of Diabetic Ketoacidosis during the prior 6 months prior to screening visit,
as diagnosed on hospital admission or as judged by the investigator.

- Adrenal insufficiency.

- Any active infection.

- Known or suspected abuse of alcohol, narcotics, or illicit drugs.

- Seizure disorder.

- Active foot ulceration.

- Severe peripheral arterial disease characterized by ischemic rest pain or severe
claudication.

- Major surgical operation within 30 days prior to screening.

- Use of an investigational drug within 30 days prior to screening.

- Chronic usage of any immunosuppressive medication (such as cyclosporine, azathioprine,
sirolimus, or tacrolimus).

- Bleeding disorder, treatment with warfarin, or platelet count below 50,000.

- Allergy to lispro insulin.

- Allergy to acrylate-based skin adhesives.

- Need for uninterrupted treatment of acetaminophen.

- Current administration of oral or parenteral corticosteroids.

- Any life threatening disease, including malignant neoplasms and medical history of
malignant neoplasms within the past 5 years prior to screening (except basal and
squamous cell skin cancer).

- Beta blockers or non-dihydropyridine calcium channel blockers.

- Current use of any medication intended to lower glucose other than insulin (ex. use of
liraglutide).

- Any clinically significant disease or disorder which in the opinion of the
Investigator may jeopardize the subject's safety or compliance with the protocol.