Outpatient Control-to-Range: System and Monitoring Testing
Outpatient Control-to-Range: System and Monitoring Testing
A single arm, single treatment study is proposed to assess the feasibility of the AP Platform
 (cell phone + Control to Range system) outside of a hospital based clinical research center.
Automated closed-loop control (CLC) of blood glucose, known as "artificial pancreas" (AP) can
 have tremendous impact on the health and lives of people with type 1 diabetes (T1DM). This
 inter-institutional and international research team has been on the forefront of CLC
 developments since the beginning of the Juvenile Diabetes Research Foundation (JDRF)
 Artificial Pancreas initiative in 2006. Thus far, the investigators have conducted three
 closed-loop control clinical trials (totaling 60 subjects with T1DM), which demonstrated
 significantly more time in an acceptable "target" blood glucose range during CLC, and
 significantly fewer hypoglycemic events during CLC compared to open loop. The overall
 objective is to sequentially test, validate, obtain regulatory approval for, and deploy at
 home, a closed-loop Control-to-Range (CTR) system comprised of two algorithmic components: a
 Safety Supervision Module (SSM) and a Hypoglycemia Mitigation Module (HMM). The SSM will
 monitor the safety of the subject's continuous subcutaneous insulin infusion pump (CSII) to
 prevent hypoglycemia and will also monitor the integrity of continuous glucose monitor (CGM)
 data for signal sensor deviations or loss of sensitivity. The HMM will be responsible for the
 optimal regulation of postprandial hyperglycemic excursions through correction boluses.

 This study will test the ability of AP Platform to (1) run CTR in an outpatient setting, and
 (2) be remotely monitored. Specifically, this study involves studying adults with T1DM who
 are experienced insulin pump users. Subjects will spend two nights (~42 hours) in a local
 hotel, during which the AP Platform will be remotely monitored in an adjacent hotel room for
 validation that remote system monitoring can successfully occur. During the study, study
 subjects will be responsible for operating the CTR system with nursing and technicians
 available for additional support. A study physician and senior engineer will be on call.

 Five subjects each will be enrolled at University of Virginia and the University of
 California, Santa Barbara.
INCLUSION CRITERIA

 1. ≥21 and <65 years old

 2. Clinical diagnosis of type 1 diabetes mellitus:

 -  Criteria for documented hyperglycemia (at least 1 criterion must be met):

 -  Fasting glucose ≥126 mg/dL - confirmed

 -  Two-hour Oral Glucose Tolerance Test (OGTT) glucose ≥200 mg/dL - confirmed

 -  HbA1c ≥6.5% documented by history - confirmed

 -  Random glucose ≥200 mg/dL with symptoms

 -  No data at diagnosis is available but the participant has a convincing
 history of hyperglycemia consistent with diabetes

 -  Criteria for requiring insulin at diagnosis (at least 1 criterion must be met):

 -  Participant required insulin at diagnosis and continually thereafter

 -  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

 -  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

 3. Use of an insulin pump to treat his/her diabetes for at least 1 year

 4. Actively using an insulin pump with bolus calculator feature including predefined
 parameters for carbohydrate ratio, insulin sensitivity factor, target blood glucose
 (BG) and active insulin.

 5. HbA1c between 6.0% - 9.0% as measured with DCA2000 or equivalent device

 6. Not currently known to be pregnant, breast feeding, or intending to become pregnant
 (females)

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

 8. Willingness to avoid consumption of acetaminophen-containing products during the study
 interventions

 9. If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, have
 stability on the medication for at least 2 months prior to enrollment in the study

 EXCLUSION CRITERIA

 1. Diabetic ketoacidosis within the 6 months prior to enrollment

 2. Severe hypoglycemia resulting in seizure, loss of consciousness, or 3rd party
 assistance in the 12 months prior to enrollment

 3. Subject reports that he/she has hypoglycemia unawareness with severe low blood sugars
 (e.g. <50 mg/dL without symptoms)

 4. Pregnancy; breast feeding, or intention of becoming pregnant

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

 6. Conditions which may increase the risk of hypoglycemia such as any cardiac
 disorder/arrhythmia, uncontrolled coronary artery disease during the previous year
 (e.g. history of myocardial infarction, acute coronary syndrome, therapeutic coronary
 intervention, coronary bypass or stenting procedure, stable or unstable angina,
 episode of chest pain of cardiac etiology with documented EKG changes, or positive
 stress test or catheterization with coronary blockages >50%), congestive heart
 failure, history of cerebrovascular event, seizure disorder, syncope, adrenal
 insufficiency, neurologic disease or atrial fibrillation

 7. Hematocrit <40% (males) and <35% (females)

 8. History of a systemic or deep tissue infection with methicillin-resistant staph aureus
 or Candida albicans

 9. Use of a device that may pose electromagnetic compatibility issues and/or
 radiofrequency interference with the CGM (implantable cardioverter-defibrillator,
 electronic pacemaker, neurostimulator, intrathecal pump, and cochlear implants)

 10. Anticoagulant therapy other than aspirin

 11. Oral steroids

 12. Medical condition requiring use of an acetaminophen-containing medication that cannot
 be withheld for the study admissions.

 13. Psychiatric disorders that would interfere with study tasks (e.g. inpatient
 psychiatric treatment within 6 months prior to enrollment)

 14. Mental incapacity, unwillingness or language barriers precluding adequate
 understanding or cooperation

 15. Known current or recent alcohol or drug abuse

 16. Medical conditions that would make operating a CGM, cell phone, or insulin pump
 difficult (e.g. blindness, severe arthritis, immobility)

 17. Any skin condition that prevents sensor or pump placement on the abdomen or arm (e.g.
 bad sunburn, pre-existing dermatitis, intertrigo, psoriasis, extensive scarring,
 cellulitis)

 18. Impaired hepatic function measured as alanine aminotransferase or aspartate
 aminotransferase ≥three times the upper reference limit

 19. Impaired renal function measured as creatinine >1.2 times above the upper limit of
 normal

 20. Uncontrolled microvascular (diabetic) complications (other than diabetic
 non-proliferative retinopathy), such as current proliferative diabetic retinopathy,
 known diabetic nephropathy (other than microalbuminuria with normal creatinine) or
 neuropathy requiring treatment

 21. Active gastroparesis requiring current medical therapy

 22. If taking 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

 23. Uncontrolled thyroid disease

 24. Known bleeding diathesis or dyscrasia

 25. Known allergy to medical adhesives, components of the insulin pump insertion set or
 continuous glucose monitor sensor

 26. Active enrollment in another clinical trial

 27. Unwillingness to withhold dietary supplements two weeks prior to admission and for the
 duration of the study participation

 28. Use of anti-diabetic agents other than CSII including long-acting insulin,
 intermediate-acting insulin, metformin, sulfonylureas, meglitinides,
 thiazolidinediones, DPP-IV inhibitors, glucagon-like peptide 1 agonists, and
 alpha-glucosidase inhibitors

 29. Subjects with basal rates less than 0.05.

 RESTRICTIONS ON USE OF OTHER DRUGS OR TREATMENTS.

 1. Use of anti-diabetic agents other than CSII including long-acting insulin,
 intermediate-acting insulin, metformin, sulfonylureas, meglitinides,
 thiazolidinediones, DPP-IV inhibitors, glucagon-like peptide 1 agonists, and
 alpha-glucosidase inhibitors.

 2. Oral steroids are excluded

 3. Anticoagulant therapy other than aspirin is excluded

 4. Acetaminophen will not be allowed while the continuous glucose monitor is in use

 5. Dietary supplements will be withheld two weeks prior to admission and for the duration
 of study participation

 6. Medications that block symptoms of hypoglycemia, including but not limited to beta
 blockers