Pilot Study 3 of Outpatient Control-to-Range: Safety and Efficacy With Day-and-Night In-Home Use

Pilot Study 3 of Outpatient Control-to-Range: Safety and Efficacy With Day-and-Night In-Home Use

The purpose of this study is to see if an automated insulin management system ("study system") can safely be used at home to manage blood sugar. The study system includes (1) a CGM that measures glucose levels, (2) a computer program on a smartphone that determines how much insulin is needed and allows the study participant user to control the whole system, and (3) an insulin pump that delivers the insulin. The CGM will be from Dexcom. The pump will be from Roche. The CGM and pump are similar to the devices that are currently available for people to purchase and use. However, the smartphone device, the CGM sensor type used with it, and the overall study system can only be used for research at this time.

The study will be completed by about 24 individuals at 6 centers in the United States and Europe. This study has several phases and will take about 11-14 weeks to complete depending on whether the study participant is a CGM user or not.

At selected sites (based on subject eligibility and availability), approximately 10-20 subjects who exhibit safe and competent use of the system at home will be given the option to continue home use of the system in Day-and-Night Closed-Loop mode for up to 5 months.

The study phases are as follows:

• Screening visit to see if you are eligible for the study and to determine how long you will need to use the study CGM (visit 1)
• Up to 3 weeks using the study CGM (depends on your current CGM use), followed by an office visit (visit 2)
• 2 weeks using the study insulin pump and study CGM together
• Full day visit in clinic or hotel for training using the system (visit 3)
• 1 week using the system without automated insulin delivery or suspension
• 2-day hotel or clinic visit for closed-loop training (visit 4),
• 16-19 days using the system in the evening and overnight only followed by an office visit (visit 5)
• 16-19 days using the system for the full 24 hours
• Final study clinic visit (visit 6)
• Option 5 month extension phase of day-and-night closed-loop home use

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.
2. Age >=18 to <70 years.
3. HbA1c <10.0%; if HbA1c <6.0% then total daily insulin must be >=0.5 U/kg
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. Hypoglycemia awareness as demonstrated by a Clarke Hypoglycemia Awareness score of 2 or lower
8. Access to internet and cell phone service at home, and a computer for downloading device data.
9. Living with 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.
10. Commitment to maintaining uninterrupted availability via cell phone and avoiding any overnight travel for the duration of each two-week period using the closed-loop system.
11. An understanding of and willingness to follow the protocol and sign the informed consent.

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. History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)

6. Cystic fibrosis.

7. 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 for either the subject or the subject's primary care giver (i.e., parent or guardian)
   • 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); 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); 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)

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. Current use of the following drugs and supplements:

• Acetaminophen
• Any medication being taken to lower blood glucose, such as Pramlintide, Metformin, GLP-1 Analogs such as Liraglutide, and nutraceuticals intended to lower blood glucose
• Beta blockers
• Oral or injectable glucocorticoids
• Any other medication that the investigator believes is a contraindication to the subject's participation