Feasibility of Outpatient Closed Loop Control With the Bionic Pancreas in Cystic Fibrosis Related Diabetes

Inclusion Criteria

- Age ≥ 18 years and have had a diagnosis of CFRD managed using either an insulin pump
or multiple daily injections (insulin dose must be ≥0.1u/kg/day)

- Live within a 120 minute drive-time radius of the central monitoring location

- Willing to remain within a 250 mile radius of the central monitoring location
throughout the study. No air travel will be allowed due to the inability to remotely
monitor patients while they are flying.

- Willing to wear one or two infusion sets and one Dexcom CGM sensor and change sets
frequently (at least one new glucagon infusion set daily during bi-hormonal arms, and
insulin infusion set every other day throughout the study)

- Have a mobile phone they will have access to at all times throughout the study for
making contact with study staff

- Have someone over 18 years of age who lives with them, has access to where they sleep,
is willing to be in the house when the subject is sleeping, and is willing to receive
calls from the study staff and check the welfare of the study subject if telemetry
shows a technical problem or severe biochemical hypoglycemia without subject response
and the subject does not answer their telephone (up to two individuals can share this
role, but they must be willing to carefully coordinate with each other and the subject
so that one of them is clearly designated as having this responsibility at any given
time)

No subjects will be excluded on the basis of gender or race.

Exclusion Criteria

- 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 Subjects must use
acceptable contraception for the two weeks prior to the study, throughout the study
and for the two weeks following the study.

Acceptable contraception methods include:

Oral contraceptive pill (OCP) Intrauterine Device (IUD, hormonal or copper) Male condoms
Female condoms Diaphragm or cervical cap with spermicide Contraceptive patch (such as
OrthoEvra) Contraceptive implant (such as Implanon, Nexplanon) Vaginal ring (such as
NuvaRing) Progestin shot (such as Depo-Provera) Male partner with a vasectomy proven to be
effective by semen analysis

- Need to go outside of the designated geographic boundaries during the study

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

- Unwilling or unable to refrain from drinking more than 2 drinks in an hour or more
than 4 drinks in a day during the trial

- Unwilling or unable or to avoid 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 severe 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 (eGFR<30)

- 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)

- Abnormal EKG consistent with coronary artery disease or increased risk of malignant
arrhythmia including, but not limited to, evidence of active ischemia, prior
myocardial infarction, proximal LAD critical stenosis (Wellen's sign), prolonged QT
interval (> 440 ms). Non-specific ST segment and T wave changes are not grounds for
exclusion in the absence of symptoms or history of heart disease. A reassuring
evaluation by a cardiologist after an abnormal EKG finding may allow participation.

- 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.

- Unable to completely avoid acetaminophen for duration of study

- 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

- History of eating disorder within the last 2 years, such as anorexia, bulimia, or
diabulemia or omission of insulin to manipulate weight

- History of intentional, inappropriate administration of insulin leading to severe
hypoglycemia requiring treatment

- Use of oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, DPP-4
inhibitors, SGLT-2 inhibitors) or non-insulin injectable (GLP-1 agonists, amylin)
anti-diabetic medications

- Lives in or frequents areas with poor Verizon wireless network coverage (which would
prevent remote monitoring)

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

- Currently receiving (or likely to need during the study period): immunosuppressant
therapy, chemotherapy, anticoagulant/antithrombotic therapy (excluding aspirin).

- History of lung or liver transplant

- Anticipated lung transplant (on transplant list)

- No acute pulmonary exacerbation or hospitalizations within the past 4 weeks or
treatment with IV antibiotics in the past 4 weeks.