USS Virginia Closed-Loop for Overnight Control in Type 1 Diabetes
USS Virginia Closed-Loop for Overnight Control in Type 1 Diabetes
The purpose of this study is to use the USS Virginia Closed-Loop system for overnight insulin
 delivery in adults with Type 1 Diabetes (T1DM) in an outpatient setting to evaluate the
 system's ability to significantly improve blood glucose levels. This protocol will test the
 feasibility of "bedside" closed-loop control - an approach comprised of standard
 sensor-augmented pump therapy during the day using off-the-shelf devices and overnight
 closed-loop control using experimental devices in an outpatient setting. The rationale for
 this study is as follows: we anticipate that closed-loop control may ultimately be adopted by
 patients with T1DM in a selective manner. Patient may choose to start using these systems for
 overnight control only, e.g. to alleviate the well documented fear of hypoglycemia while
 asleep. To test this paradigm of "bedside" closed-loop control, subjects will be studied with
 continuous glucose monitoring (CGM)-augmented usual pump therapy during the day followed by
 overnight use of USS Virginia Closed Loop Control.
The subject will participate in both the Experimental and the Control Admissions. The order
 of the two admissions will be randomized. During the Control Admission at home, the subject
 will use the study insulin pump along with a continuous glucose monitor receiver. During the
 Experimental Admission, the subject will be the research house/hotel where the subject will
 be in control of the DiAs. Participation in this study will require 5 study visits over 11-14
 weeks.
Inclusion Criteria:

 1. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least
 one year and using insulin for at least 1 year and an insulin pump for at least 6
 months

 - Criteria for documented hyperglycemia (at least 1 must be met): i. Fasting glucose
 ≥126 mg/dL ii. Two-hour Oral Glucose Tolerance Test (OGTT) glucose ≥200 mg/dL iii.
 HbA1c ≥6.5% documented 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.

 - 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

 2. Age ≥21 to <65 years

 3. HbA1c <10.0%

 4. For females, not currently known to be pregnant If female and sexually active, must
 agree to use a form of contraception to prevent pregnancy while a participant in the
 study. A negative urine pregnancy test will be required for all premenopausal women
 who are not surgically sterile. Subjects who become pregnant will be discontinued from
 the study.

 5. Demonstration of proper mental status and cognition for the study

 6. Currently using insulin-to-carbohydrate ratio to calculate meal bolus sizes

 7. Ability to access the Internet and upload CGM data via the DexCom company software
 during the data collection period.

 8. Willingness to remain within approximately 30 miles radius of study site during the
 day time hours of Visit 4.

 9. An understanding of and willingness to follow the protocol and sign the informed
 consent

 Additional Inclusion Criteria for UVA subjects only who participate in the 5 days at-home
 portion

 -  Availability of a significant other or family member committed to participating in all
 training activities, knowledgeable at all times of the participant's location, and
 being present and available to provide assistance when system is being used at night

 -  Commitment to maintaining uninterrupted availability via cell phone and avoiding any
 overnight travel for the duration of the period of time using the closed-loop system
 at home.

 -  Access to internet and cell phone service at home

 Exclusion Criteria:

 1. Admission for diabetic ketoacidosis in the 12 months prior to enrollment

 2. Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months
 prior to enrollment

 3. History of a seizure disorder (except hypoglycemic seizure), unless written clearance
 is received from a neurologist

 4. Coronary artery disease or heart failure, unless written clearance is received from a
 cardiologist

 5. Cystic fibrosis

 6. A known medical condition that in the judgment of the investigator might interfere
 with the completion of the protocol such as the following examples:

 -  Inpatient psychiatric treatment in the past 6 months

 -  Presence of a known adrenal disorder

 -  Abnormal liver function test results (Transaminase >2 times the upper limit of
 normal); testing required for subjects taking medications known to affect liver
 function or with diseases known to affect liver function

 -  Abnormal renal function test results (calculated GFR <60 mL/min/1.73m2); testing
 required for subjects with diabetes duration of greater than 5 years post onset
 of puberty

 -  Active gastroparesis

 -  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

 -  Uncontrolled thyroid disease (TSH undetectable or >10 mlU/L); testing required
 within three months prior to admission for subjects with a goiter, positive
 antibodies, or who are on thyroid hormone replacement, and within one year
 otherwise

 -  Abuse of alcohol or recreational drugs

 -  Infectious process not anticipated to resolve prior to study procedures (e.g.
 meningitis, pneumonia, osteomyelitis).

 -  Uncontrolled arterial hypertension (Resting diastolic blood pressure >90 mmHg
 and/or systolic blood pressure >160 mmHg).

 -  Oral steroids

 -  Uncontrolled microvascular complications such as current active proliferative
 diabetic retinopathy defined as proliferative retinopathy requiring treatment
 (e.g. laser therapy) in the past 12 months.

 7. A recent injury to body or limb, muscular disorder, use of any medication, any
 carcinogenic disease, or other significant medical disorder if that injury, medication
 or disease in the judgment of the investigator will affect the completion of the
 protocol

 8. Basal Rates <0.01 units/hour.

 9. Current use of the following drugs and supplements:

 -  Acetaminophen

 -  Any medication being taken to lower blood glucose, such as Pramlintide,
 Metformin, glucagon-like peptide (GLP)-1 Analogs such as Liraglutide, and
 nutraceuticals intended to lower blood glucose

 -  Beta blockers

 -  Any other medication that the investigator believes is a contraindication to the
 subject's participation