The iLet Introduction Study: A Feasibility Study of the iLet, a Fully Integrated Bihormonal Bionic Pancreas

The iPhone bionic pancreas has been used in earlier studies, during which volunteers used the
system for up to 11 days at a time while living their normal lives at home and work. The iLet
bionic pancreas has never been tested in humans. In this new study, volunteers will
participate in a training visit to learn how both devices work. They will then use the
iPhone-based BP for 1 day and the iLet BP for 1 day in random order using Lilly glucagon.
They will then use the iLet BP for one additional day using Xeris Xerisol glucagon (a stable
formulation of human glucagon).

A custom infusion set is required for this bihormonal system, to prevent future consumers
from being able to accidentally swap their insulin and glucagon reservoirs and infusion sets,
which could be potentially fatal. Previous experiments have demonstrated flaws in the
infusion set design, requiring human experiments to be suspended and modifications to the
infusion set be made. We believe the current infusion set has addressed these flaws by
incorporating an anti-coring heel and a tri-beveled needle, and the infusion set sub-study is
designed to isolate and study the infusion set function before further experiments using the
iLet BP are conducted.

Inclusion Criteria:

iPhone and iLet BP experiments

- Age ≥ 18 years and have had clinical type 1 diabetes for at least one year

- Diabetes managed using an insulin pump for ≥ 6 months

- Prescription medication regimen stable for > 1 month (except for medications that will
not affect the safety of the study and are not expected to affect any outcome of the
study, in the judgment of the principal investigator)

iLet Infusion Set Sub-Study

- Age ≥ 18 years and have had clinical type 1 diabetes for at least one year

- Diabetes managed using an insulin pump for ≥ 6 months

Exclusion Criteria:

iPhone and iLet BP experiments

- Unable to provide informed consent (e.g. impaired cognition or judgment)

- Unable to safely comply with study procedures and reporting requirements (e.g.
impairment of vision or dexterity that prevents safe operation of the bionic pancreas,
impaired memory, unable to speak and read English)

- Current participation in another diabetes-related clinical trial that, in the judgment
of the principal investigator, will compromise the results of this study or the safety
of the subject

- Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the
immediate future, or sexually active without use of contraception

- Current alcohol abuse (intake averaging > 3 drinks daily in last 30 days), use of
marijuana within 1 month of enrollment, or other substance abuse (use within the last
6 months of controlled substances other than marijuana without a prescription)

- Unwilling or unable to refrain on the study days from:acetaminophen in any form, use
of marijuana, use of drugs that may dull the sensorium, reduce sensitivity to symptoms
of hypoglycemia, or hinder decision making during the period of participation in the
study (use of beta blockers will be allowed as long as the dose is stable and the
subject does not meet the criteria for hypoglycemia unawareness while taking that
stable dose, but use of benzodiazepines or narcotics, even if by prescription, may be
excluded according to the judgment of the principal investigator)

- History of liver disease that is expected to interfere with the anti-hypoglycemia
action of glucagon (e.g. liver failure or cirrhosis). Other liver disease (i.e. active
hepatitis, steatosis, active biliary disease, any tumor of the liver, hemochromatosis,
glycogen storage disease) may exclude the subject if it causes significant compromise
to liver function or may do so in an unpredictable fashion.

- Renal failure on dialysis

- Personal history of cystic fibrosis, pancreatitis, pancreatic tumor, or any other
pancreatic disease besides type 1 diabetes

- Any known history of coronary artery disease including, but not limited to, history of
myocardial infarction, stress test showing ischemia, history of angina, or history of
intervention such as coronary artery bypass grafting, percutaneous coronary
intervention, or enzymatic lysis of a presumed coronary occlusion)

- Congestive heart failure (established history of CHF, lower extremity edema,
paroxysmal nocturnal dyspnea, or orthopnea)

- History of TIA or stroke

- Seizure disorder, history of any non-hypoglycemic seizure within the last two years,
or ongoing treatment with anticonvulsants

- History of hypoglycemic seizures (grand-mal) or coma in the last year

- History of pheochromocytoma: fractionated metanephrines will be tested in patients
with history increasing the risk for a catecholamine secreting tumor: Episodic or
treatment refractory (requiring 4 or more medications to achieve normotension)
hypertension, Paroxysms of tachycardia, pallor, or headache, Personal or family
history of MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease

- History of adrenal disease or tumor

- Hypertension with systolic BP ≥160 mm Hg or diastolic BP ≥100 despite treatment

- Untreated or inadequately treated mental illness (indicators would include symptoms
such as psychosis, hallucinations, mania, and any psychiatric hospitalization in the
last year), or treatment with anti-psychotic medications that are known to affect
glucose regulation.

- Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be
susceptible to RF interference

- History of adverse reaction to glucagon (including allergy) besides nausea and
vomiting

- Established history of allergy or severe reaction to adhesive or tape that must be
used in the study

- Use of oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, DPP-4
inhibitors, SGLT-2 inhibitors) anti-diabetic medications

- Hemoglobin < 12 g/dl

- Any factors that, in the opinion of the principal investigator would interfere with
the safe completion of the study

iLet Infusion Set Sub-Study

- Unable to provide informed consent (e.g. impaired cognition or judgment)

- Unable to safely comply with study procedures and reporting requirements (e.g.
impairment of vision or dexterity that prevents safe operation of their insulin pump,
impaired memory, unable to speak and read English)

- Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the
immediate future, or sexually active without use of contraception

- Hemoglobin < 11 g/dl

- Unable to establish IV access, or subject reports difficult IV access in the past

- History of allergy or severe reaction to adhesive or tape that must be used in the
study