The iLet Introduction Study: A Feasibility Study of the iLet, a Fully Integrated Bihormonal Bionic Pancreas

Study Overview
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Brief Summary
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This study will compare two different models of a wearable bionic pancreas device (the iPhone-based bionic pancreas vs. the iLet bionic pancreas) in adult participant with type 1 diabetes. Both bionic pancreas devices measure glucose levels every five minutes and then give insulin and/or glucagon automatically to regulate the blood glucose (BG).

Detailed Description
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The iPhone bionic pancreas has been used in earlier studies, during which volunteers used the system for up to 11 days at a time while living their normal lives at home and work. The iLet bionic pancreas has never been tested in humans. In this new study, volunteers will participate in a training visit to learn how both devices work. They will then use the iPhone-based BP for 1 day and the iLet BP for 1 day in random order using Lilly glucagon. They will then use the iLet BP for one additional day using Xeris Xerisol glucagon (a stable formulation of human glucagon). A custom infusion set is required for this bihormonal system, to prevent future consumers from being able to accidentally swap their insulin and glucagon reservoirs and infusion sets, which could be potentially fatal. Previous experiments have demonstrated flaws in the infusion set design, requiring human experiments to be suspended and modifications to the infusion set be made. We believe the current infusion set has addressed these flaws by incorporating an anti-coring heel and a tri-beveled needle, and the infusion set sub-study is designed to isolate and study the infusion set function before further experiments using the iLet BP are conducted.

Official Title
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The iLet Introduction Study: A Feasibility Study of the iLet, a Fully Integrated Bihormonal Bionic Pancreas

Conditions
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Diabetes Mellitus Type 1

Intervention / Treatment
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* Device: iPhone bionic pancreas
* Device: iLet bionic pancreas
* Drug: Xeris Xerisol glucagon
* Drug: Lilly glucagon
* Device: iLet infusion set
* Device: Contact Detach infusion set


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: iPhone and iLet BP experiments Age ≥ 18 years and have had clinical type 1 diabetes for at least one year Diabetes managed using an insulin pump for ≥ 6 months Prescription medication regimen stable for > 1 month (except for medications that will not affect the safety of the study and are not expected to affect any outcome of the study, in the judgment of the principal investigator) iLet Infusion Set Sub-Study Age ≥ 18 years and have had clinical type 1 diabetes for at least one year Diabetes managed using an insulin pump for ≥ 6 months Exclusion Criteria: iPhone and iLet BP experiments 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 Current alcohol abuse (intake averaging > 3 drinks daily in last 30 days), use of marijuana within 1 month of enrollment, or other substance abuse (use within the last 6 months of controlled substances other than marijuana without a prescription) Unwilling or unable to refrain on the study days from:acetaminophen in any form, use of marijuana, 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 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 Personal history of cystic fibrosis, pancreatitis, pancreatic tumor, or any other pancreatic disease besides type 1 diabetes 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) 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. Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference 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 Use of oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, DPP-4 inhibitors, SGLT-2 inhibitors) anti-diabetic medications Hemoglobin < 12 g/dl Any factors that, in the opinion of the principal investigator would interfere with the safe completion of the study iLet Infusion Set Sub-Study 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 their insulin pump, impaired memory, unable to speak and read English) Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception Hemoglobin < 11 g/dl Unable to establish IV access, or subject reports difficult IV access in the past History of allergy or severe reaction to adhesive or tape that must be used in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: iPhone bionic pancreas - Lilly glucagon<br>iPhone based bionic pancreas using insulin lispro and Lilly glucagon. These visits will be conducted separately from the infusion set sub-study visits. | Device: iPhone bionic pancreas<br>* An experimental device composed of three parts: a continuous glucose monitor, control algorithms running on an iPhone, and drug delivery using Tandem insulin pumps<br>Drug: Lilly glucagon<br>* An aqueous formulation of human glucagon with limited stability that must be changed daily<br>* Other names: glucagon;|
| Experimental: iLet bionic pancreas - Lilly glucagon<br>iLet Bionic Pancreas using using insulin lispro and Lilly glucagon. These visits will be conducted separately from the infusion set sub-study visits. | Device: iLet bionic pancreas<br>* An experimental device that combines the functions of the iPhone-based bionic pancreas into one device.<br>Drug: Lilly glucagon<br>* An aqueous formulation of human glucagon with limited stability that must be changed daily<br>* Other names: glucagon;|
| Experimental: iLet bionic pancreas - Xerisol glucagon<br>iLet Bionic Pancreas using using insulin lispro and Xeris Xerisol glucagon. These visits will be conducted separately from the infusion set sub-study visits. | Device: iLet bionic pancreas<br>* An experimental device that combines the functions of the iPhone-based bionic pancreas into one device.<br>Drug: Xeris Xerisol glucagon<br>* A stabilized formulation of human glucagon in a solvent based primarily composed of dimethyl sulfoxide (DMSO) that has prolonged stability and can be used for multiple days in a pump<br>* Other names: Xeris glucagon;|
| Experimental: iLet infusion set<br>The infusion set sub-study will be testing just the experimental iLet infusion set in a crossover with the contact detach infusion set. These visits will be conducted separately from the iPhone and iLet bionic pancreas visits. | Device: iLet infusion set<br>* The infusion set sub-study will be studying the experimental iLet infusion set in a cross-over with the Contact Detach infusion set. These visits will be conducted separately from the iPhone and iLet BP visits.<br>|
| Active Comparator: Contact Detach infusion set<br>The infusion set sub-study will be testing just the experimental iLet infusion set in a crossover with the contact detach infusion set. These visits will be conducted separately from the iPhone and iLet bionic pancreas visits. | Device: Contact Detach infusion set<br>* The infusion set sub-study will be studying the experimental iLet infusion set in a cross-over with the Contact Detach infusion set. These visits will be conducted separately from the iPhone and iLet BP visits.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Percent Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump (Aggregate of Both Insulin and Glucagon Doses) | Average percent dose amounts calculated by the bionic pancreas control algorithm that are successfully delivered by the pump (aggregate of both insulin and glucagon doses) - primary outcome for iPhone-based BP using Lilly glucagon vs. iLet BP using Lilly glucagon | 8 hours | 
| Average Percent Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump (Glucagon Doses). | Average percent dose amounts calculated by the bionic pancreas control algorithm that are successfully delivered by the pump (glucagon doses) - - primary outcome for iLet BP using Lilly glucagon vs. iLet BP using Xeris Xerisol glucagon | 8 hours | 
| Insulin Area Under the Curve in the 3.5 Hours Following the Insulin Bolus | This applies only to the infusion set sub-study | 3.5 hours following insulin bolus | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Continuous Glucose Monitor (CGM) Glucose | The average glucose according to continuous glucose monitor readings. This only applies to the iPhone vs. iLet BP experiments. | 8 hours | 
| Percentage of Time in Each of the Following Ranges: < 50 mg/dl, < 60 mg/dl, <70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, >180 mg/dl, >250 mg/dl | Percentage of time subjects spent in each of these ranges based on continuous glucose monitor readings. This only applies to the iPhone vs iLet BP visits. | 8 hours | 
| Number of Subjects With Mean CGM Glucose < 154 mg/dl | The number of subjects who achieved a mean CGM glucose < 154 mg/dl, which correlates to an estimated hemoglobin a1c of 7%, which is the ADA goal for therapy. This applies only to the iPhone vs iLet BP experiments | 8 hours | 
| Number of Severe Hypoglycemic Events (Subject Unable to Self-treat, Requiring the Assistance of Another Person) | The number of severe hypoglycemic events subjects experience. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Average Percent Insulin Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump. | The average percentage of successfully delivered insulin doses. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Average Percent Glucagon Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump. | The average percentage of successfully delivered glucagon doses. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Average Percent Insulin Dose Amounts Successfully Issued to the Pump by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump. | The average percentage of successfully issued insulin doses that are then delivered successfully by the pump. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Average Percent Glucagon Dose Amounts Successfully Issued to the Pump by the Bionic Pancreas Control Algorithm That a Successfully Delivered by the Pump. | The average percentage of successfully issued glucagon doses that are then delivered successfully by the pump. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Average Percent of 5 Minute Steps During Which the Bionic Pancreas is Functioning Nominally in All Respects Based on Real-time CGM Data (New CGM Glucose Reading Captured, Dose Calculated, Dose Issued to Pumps | The percentage of time (measured in 5 minute steps) that the bionic pancreas is working, indicated by the presence of a CGM reading, a successful dose calculation and successful issuing of a dose. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Average Percent of 5 Minute Steps During Which the Bionic Pancreas is Functioning Nominally With or Without a New CGM Glucose Reading Captured (Dose Calculated, Dose Issued to Pumps). | The percentage of time (measured in 5 minute steps) that the bionic pancreas is working even without a CGM reading being present, indicated by a successful dose calculation and successful issuing of a dose. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| CGM Reliability Index, Calculated as Percent of Possible Values Actually Recorded by CGM. | A measure of CGM reliability, indicating the percentage of values the CGM displayed out of the total values it should have displayed in that time. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Glucagon Total Delivery Per kg of Body Mass. | The average total glucagon delivered by the bionic pancreas. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Insulin Total Delivery Per kg of Body Mass. | The average total insulin delivered by the bionic pancreas. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Number of Episodes of Symptomatic Hypoglycemia. | Number of time subjects experienced symptoms of hypoglycemia and reported that to study staff. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Total Grams of Carbohydrate Taken for Hypoglycemia. | The total grams of carbohydrates given to subjects for treatment of hypoglycemia. This applies only to the iPhone vs iLet BP experiments. | 8 hours | 
| Difference in Mean Nausea From VAS During the Study | This applies only the iPhone vs. iLet BP experiments. Subjects were given a visual analog scale measuring 100 mm and asked to draw a line to indicate their level of nausea at timepoints during the study with 100 being the worst possible nausea and 0 being no nausea. | 8 hours | 
| Average Insulin Infusion Site Pain From VAS | This applies to the iPhone vs. iLet BP experiments and the infusion set sub-study experiments. Subjects were given a visual analog scale measuring 100 mm and asked to draw a line to indicate their level of pain at timepoints during the study with 100 being the worst possible pain and 0 being no pain. | 8 hours | 
| Difference in Local Erythema and Edema According to the Draize Scale | This applies to the iPhone vs. iLet BP experiments and the infusion set sub-study experiments. The draize scale assess erythema, eschar and edema using a score from 0-4, with 4 meaning a worse outcome. | 8 hours | 
| Number of Unscheduled Infusion Set Replacements. | This applies to the iPhone vs. iLet BP experiments and the infusion set sub-study experiments. | 8 hours | 
| Number of Unscheduled CGM Sensor Changes. | This applies only to the iPhone vs. iLet BP experiments | 8 hours | 
| Insulin Area Under the Curve During the Initial 90 Minute Fasted Period | This applies only to the infusion set sub-study | 8 hours | 
| Mean Insulin Levels During the Initial 90 Minute Fasted Period | This applies only to the infusion set sub-study | 8 hours | 
| Difference Between Insulin Levels at Baseline and at 90 Minutes | This applies only to the infusion set sub-study | 8 hours | 
| Tmax After the Insulin Dose | This applies only to the infusion set sub-study | 8 hours | 
| T 1/2 Max After the Insulin Dose | This applies only to the infusion set sub-study | 8 hours | 
| C Max After the Insulin Dose | This applies only to the infusion set sub-study | 8 hours | 
| AUC in the First 30 Minutes After the Insulin Dose | This applies only to the infusion set sub-study | 8 hours | 
| AUC in the First 60 Minutes After the Insulin Dose | This applies only to the infusion set sub-study | 8 hours | 
| AUC in the First 90 Minutes After the Insulin Dose | This applies only to the infusion set sub-study | 8 hours | 
| Terminal Half Life After the Insulin Dose | This applies only to the infusion set sub-study | 8 hours | 
| Difference Between the Fasted PG Value and the PG Value at 90 Minutes | This applies only to the infusion set sub-study | Baseline Fasted State and 90 Minutes | 
| Difference in the PG Prior to the Meal and Peak Post-prandial Glucose | This applies only to the infusion set sub-study | Pre-meal PG value and peak PG value during the 3.5 hours following the meal. | 
| PG AUC in the 3.5 Hours Following the Meal | This applies only to the infusion set sub-study | 3.5 hours following the meal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bionic Pancreas, Insulin, Glucagon, Continuous Glucose Monitor