Efficacy of inControl Advice: A Decision Support System (DSS) for Diabetes

The purpose of this study is to reduce the frequency of hypoglycemia and severe hypoglycemic events in subjects who use insulin pens to treat their Type 1 Diabetes Mellitus (T1DM). Hypoglycemia is the number one fear of many individuals and families with someone who has type 1 diabetes, and this fear often prevents optimal glycemic control. It is expected that this protocol will yield increased knowledge about using a decision support system to help control the glucose level.

This study is a 12-week parallel group multi-center randomized trial designed to compare CGM+DSS with CGM alone. The DSS to be implemented contains a "smart" bolus advisor that adjusts the size of correction insulin boluses based on short term blood glucose predictions. It is able to complete this function by evaluating CGM values, insulin usage and carbohydrate intake record. It also contains an exercise advisor, a bedtime advisor, hypoglycemia risk and long-term tracker of HbA1c.

inControl-Advice, a smart-phone based medical software platform, is designed to provide advice to users. It receives data from an insulin pen and then adjustments the insulin delivery every 5 minutes. The system provides a series of real-time alerts and on-demand advice, for both dosing of insulin and ingestion of carbohydrates, based on data collected from T1DM patients (i.e. carbohydrate consumption, insulin injected, CGM) and inConrol Cloud analytics.

Eligibility Criteria:
Inclusion Criteria:

1. Willingness to provide informed consent
2. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year
3. Using basal and meal insulin (NovoLog® \[insulin aspart\], Humalog® \[insulin lispro\] or Apidra® \[insulin glulisine\]) for Intensive Insulin Therapy including carbohydrate counting and use of pre-defined parameters for glucose goal, carbohydrate ratio, and insulin sensitivity factor for at least 1 month.

   a. Acceptable basal insulin regimens include: i. Lantus® (insulin glargine) 100U/mL once or twice daily ii. Levemir® (insulin detemir) 100U/mL once or twice daily iii. Tresiba® (insulin degludec) 100U/mL once daily
4. Age ≥15.0 years old
5. Willingness to use the study basal insulin (Tresiba® \[insulin degludec\]) and meal insulin (NovoLog® \[insulin aspart\]) for the duration of the study.
6. Willingness to use the home or DSS-optimized carbohydrate counting parameters for all meal dosing and enter the information into the inControl APP (for CGM+DSS group).
7. For females, not currently known to be pregnant
8. If female and sexually active, must agree to use a highly effective form of contraception to prevent pregnancy while a participant in the study. A negative serum or 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. Also, subjects who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued.
9. Ability to access the Internet to provide data to the clinical team or to travel to the research center so that the study equipment can be downloaded.
10. Ability to have 3G or Wi-Fi to be able to use the DSS smart bolus calculator and advice given (i.e. sleep, exercise).
11. Demonstration of proper mental status and cognition for the study
12. Investigator has confidence that the subject can successfully operate all study devices and is capable of adhering to the protocol
13. If on a non-insulin hyperglycemic therapy, stability on that therapy for the prior 3 months and willingness not to alter the therapy for the study duration.

Exclusion Criteria:

1. Medical need for chronic acetaminophen
2. Use of any medication that at the discretion of the clinical protocol chair is deemed to interfere with the trial.
3. Current treatment of a seizure disorder.
4. Coronary artery disease or heart failure, unless written clearance is received from a cardiologist.
5. Hemophilia or any other bleeding disorder
6. A known medical condition, which in the opinion of the investigator or designee, would put the participant or study at risk such as the following examples:

   1. Inpatient psychiatric treatment in the past 6 months
   2. Presence of a known adrenal disorder
   3. Abnormal liver function test results (Transaminase \>3 times the upper limit of normal)
   4. Abnormal renal function test results (calculated GFR \<60 mL/min/1.73m2).
   5. Active gastroparesis requiring medical therapy
   6. Uncontrolled thyroid disease (TSH undetectable or \>10 mlU/L).
   7. Abuse of alcohol or recreational drugs
   8. Infectious process not anticipated to be resolved prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis, deep tissue infection).
   9. Uncontrolled arterial hypertension (Resting diastolic blood pressure \>100 mmHg and/or systolic blood pressure \>180 mmHg).
   10. Uncontrolled microvascular complications such as current active proliferative diabetic retinopathy defined as proliferative retinopathy requiring treatment (e.g. laser therapy or VEGF inhibitor injections) 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. Current use of the following drugs and supplements:

   k. Regular acetaminophen user, or not willing to suspend acetaminophen 24 hours before and during the entire length of the trial l. Oral steroids m. Any other medication that the investigator believes is a contraindication to the subject's participation
9. Participation in another pharmaceutical or device trial at the time of enrollment or during the study