Clinical trial NCT02701257: The iLet Introduction Study: A Feasibility Study of the iLet, a Fully Integrated Bihormonal Bionic Pancreas
Official title: The iLet Introduction Study: A Feasibility Study of the iLet, a Fully Integrated Bihormonal Bionic Pancreas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetes Mellitus Type 1
Keywords: Bionic Pancreas
Insulin
Glucagon
Continuous Glucose Monitor
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Boston University
First posted: 2016-03-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 8 hours
measure: Average Percent Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump (Glucagon Doses).
timeFrame: 8 hours
measure: Insulin Area Under the Curve in the 3.5 Hours Following the Insulin Bolus
timeFrame: 3.5 hours following insulin bolus
Secondary outcomes:
measure: Average Continuous Glucose Monitor (CGM) Glucose
timeFrame: 8 hours
measure: 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
timeFrame: 8 hours
measure: Number of Subjects With Mean CGM Glucose < 154 mg/dl
timeFrame: 8 hours
measure: Number of Severe Hypoglycemic Events (Subject Unable to Self-treat, Requiring the Assistance of Another Person)
timeFrame: 8 hours
measure: Average Percent Insulin Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump.
timeFrame: 8 hours
measure: Average Percent Glucagon Dose Amounts Calculated by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump.
timeFrame: 8 hours
measure: Average Percent Insulin Dose Amounts Successfully Issued to the Pump by the Bionic Pancreas Control Algorithm That Are Successfully Delivered by the Pump.
timeFrame: 8 hours
measure: Average Percent Glucagon Dose Amounts Successfully Issued to the Pump by the Bionic Pancreas Control Algorithm That a Successfully Delivered by the Pump.
timeFrame: 8 hours
measure: 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
timeFrame: 8 hours
measure: 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).
timeFrame: 8 hours
measure: CGM Reliability Index, Calculated as Percent of Possible Values Actually Recorded by CGM.
timeFrame: 8 hours
measure: Glucagon Total Delivery Per kg of Body Mass.
timeFrame: 8 hours
measure: Insulin Total Delivery Per kg of Body Mass.
timeFrame: 8 hours
measure: Number of Episodes of Symptomatic Hypoglycemia.
timeFrame: 8 hours
measure: Total Grams of Carbohydrate Taken for Hypoglycemia.
timeFrame: 8 hours
measure: Difference in Mean Nausea From VAS During the Study
timeFrame: 8 hours
measure: Average Insulin Infusion Site Pain From VAS
timeFrame: 8 hours
measure: Difference in Local Erythema and Edema According to the Draize Scale
timeFrame: 8 hours
measure: Number of Unscheduled Infusion Set Replacements.
timeFrame: 8 hours
measure: Number of Unscheduled CGM Sensor Changes.
timeFrame: 8 hours
measure: Insulin Area Under the Curve During the Initial 90 Minute Fasted Period
timeFrame: 8 hours
measure: Mean Insulin Levels During the Initial 90 Minute Fasted Period
timeFrame: 8 hours
measure: Difference Between Insulin Levels at Baseline and at 90 Minutes
timeFrame: 8 hours
measure: Tmax After the Insulin Dose
timeFrame: 8 hours
measure: T 1/2 Max After the Insulin Dose
timeFrame: 8 hours
measure: C Max After the Insulin Dose
timeFrame: 8 hours
measure: AUC in the First 30 Minutes After the Insulin Dose
timeFrame: 8 hours
measure: AUC in the First 60 Minutes After the Insulin Dose
timeFrame: 8 hours
measure: AUC in the First 90 Minutes After the Insulin Dose
timeFrame: 8 hours
measure: Terminal Half Life After the Insulin Dose
timeFrame: 8 hours
measure: Difference Between the Fasted PG Value and the PG Value at 90 Minutes
timeFrame: Baseline Fasted State and 90 Minutes
measure: Difference in the PG Prior to the Meal and Peak Post-prandial Glucose
timeFrame: Pre-meal PG value and peak PG value during the 3.5 hours following the meal.
measure: PG AUC in the 3.5 Hours Following the Meal
timeFrame: 3.5 hours following the meal
Other outcomes:
Locations:
city: Boston
country: United States
facility: MGH Diabetes Research Center
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Steven J Russell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: