Clinical trial NCT02092220: A Multicenter Study of Outpatient Automated Blood Glucose Control With a Bihormonal Bionic Pancreas
Official title: A Multicenter Study of Outpatient Automated Blood Glucose Control With a Bihormonal Bionic Pancreas
Study type: INTERVENTIONAL
Overall status: COMPLETED
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: 2014-03-20
Enrollment: 48
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 test the hypothesis that a wearable bionic pancreas system that automatically delivers insulin and glucagon can provide superior regulation of glycemia versus usual care for adults with type 1 diabetes.

Please note that all participants must work or attend school at one of the following campuses: Massachusetts General Hospital in Boston, MA; University of Massachusetts Medical Center in Worcester, MA; University of North Carolina in Chapel Hill, NC; Stanford University in Palo Alto, CA.


Eligibility criteria: Inclusion Criteria:

* 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 judgement of the site principal investigator).
* Employee or student working or studying during most of the week at one of the participating campuses (Massachusetts General Hospital in Boston, MA; University of Massachusetts Medical Center in Worcester, MA; University of North Carolina in Chapel Hill, NC; Stanford University in Palo Alto, CA)
* Lives within a 30 minute drive-time radius of the central monitoring location for one of the study sites
* Willing to remain within a 60 minute drive-time radius of the central monitoring location for one of the study sites during each of the 11-day study arms
* Have someone over 18 years of age who lives with them, has access to where they sleep, is willing to be in the house when the subject is sleeping, and is willing to receive calls from the study staff and check the welfare of the study subject if telemetry shows a technical problem or severe biochemical hypoglycemia without subject response and the subject does not answer their telephone (up to two individuals can share this role, but they must be willing to carefully coordinate with each other and the subject so that one of them is clearly designated as having this responsibility at any given time)
* Willing to wear two infusion sets and continuous glucose monitor (CGM) sensor and change sets frequently (at least one new glucagon infusion set daily)

Exclusion Criteria:

* 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 \[positive urine human chorionic gonadotropin (HCG)\] breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception
* Need to go outside of the designated geographic boundaries during either arm of the study
* 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 from drinking more than 2 drinks in an hour or more than 4 drinks in a day or use of marijuana during the trial
* Unwilling or unable or to avoid 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)
* Abnormal electrocardiogram (EKG) consistent with coronary artery disease or increased risk of malignant arrhythmia including, but not limited to, evidence of active ischemia, prior myocardial infarction, proximal left anterior descending coronary artery (LAD) critical stenosis (Wellen's sign), prolonged QT interval (\> 440 ms). Non-specific ST segment and T wave changes are not grounds for exclusion in the absence of symptoms or history of heart disease. A reassuring evaluation by a cardiologist after an abnormal EKG finding may allow participation.
* Congestive heart failure (CHF) \[established history of CHF, lower extremity edema, paroxysmal nocturnal dyspnea, or orthopnea\]
* History of transient ischaemic attack (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 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 multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B), neurofibromatosis, or von Hippel-Lindau disease
* History of adrenal disease or tumor
* Hypertension with systolic blood pressure (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 radio-frequency (RF) interference
* Unable to completely avoid acetaminophen for duration of study
* 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
* History of eating disorder such as anorexia, bulimia, or diabulemia or omission of insulin to manipulate weight
* History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment
* Use oral \[e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter 2 (SGLT-2) inhibitors\] anti-diabetic medications
* Lives in or frequents areas with poor Verizon wireless network coverage (which would prevent remote monitoring)
* Any factors that, in the opinion of the site principal investigator or overall principal investigator, would interfere with the safe completion of the study

Primary outcomes:
measure: Mean Continuous Glucose Monitoring Glucose (CGMG) Values During Days 2 to 11
timeFrame: Days 2 to 11 of each period
measure: Percentage of Time Spent With CGMG Concentration < 60 mg/dL During Days 2 to 11
timeFrame: Days 2 to 11 of each period
Secondary outcomes:
measure: Mean CGMG Values
timeFrame: Day 1 and Days 1 to 11 in each period
measure: Percentage of Time With CGMG Concentration by Ranges During Day 1
timeFrame: Day 1 of each period
measure: Percentage of Time With CGMG Concentration by Ranges During Days 1 to 11
timeFrame: Days 1 to 11 of each period
measure: Percentage of Time With CGMG Concentration by Ranges During Days 2 to 11
timeFrame: Days 2 to 11 of each period
measure: Percentage of Participants With Mean CGMG < 154 mg/dl
timeFrame: Day 1, Days 2 to11, Days 1 to11 of each period
measure: Number of Hypoglycemic Events (< 70 mg/dL, < 60 mg/dL, <50 mg/dL)
timeFrame: Days 1-11
measure: Percentage of Days That CGM Was Used by Participants as Part of Their Usual Care
timeFrame: Days 1-11 of each period
measure: Glycated Albumin on Day 12
timeFrame: Day 12 of each period
measure: 1,5-anhydroglucitol on Day 12
timeFrame: Day 12 of each period
measure: Anti-Insulin and Anti-Glucagon Antibodies on Day 12
timeFrame: Day 12 of each period
measure: Number of Participants With Severe Hypoglycemic Events
timeFrame: 11 days of each period
measure: Number of Episodes of Symptomatic Hypoglycemia
timeFrame: Day 1, Days 1 to 11 and Days 2 to 11 of each period
measure: Number of Reported Carbohydrate Interventions for Hypoglycemia
timeFrame: Day 1, Days 1 to 11 and Days 2 to 11 of each period
measure: Total Grams of Carbohydrate Taken for Hypoglycemia
timeFrame: Day 1, Days 1 to 11 and Days 2 to 11 of each period
measure: Insulin Total Daily Dose
timeFrame: Day 1, Days 1 to 11, Days 2 to 11 of each period
measure: Glucagon Total Daily Dose Levels in the Bionic Pancreas Arm
timeFrame: Day 1, Days 2 to 11, Days 1 to 11 of each period
measure: Mean Glucose Target Set by User (Time-weighted Average Over Study Period) in the Bionic Pancreas Arm
timeFrame: Day 1, Days 2 to 11, Days 1 to11, Overall, Daytime, Nighttime of each period
measure: Percentage of Time Bionic Pancreas Off-line or Not Functioning Properly
timeFrame: 11 days
measure: Mean Nausea Index Score Using a Visual Analog Scale (VAS)
timeFrame: Day 1, Days 1 to 11, Days 2 to 11 and each individual day 2 to 11 of each period
measure: Change From Baseline in Body Weight
timeFrame: Baseline and Day 12 of each period
measure: Change From Baseline in Hemoglobin
timeFrame: Baseline and Day 12 of each period
measure: Number of Participants With Skin Rash
timeFrame: 11 days of each period
Other outcomes:
measure: Reliability Index, Calculated as Percent of Possible Values Actually Recorded by CGM
timeFrame: 11 days
measure: Number of Unscheduled Infusion Set Replacements
timeFrame: 11 days
measure: Mean Daily Basal Insulin Dose
timeFrame: Day 1, Days 2 to 11, each individual day 2 to 11 of each period
measure: Mean Daily Bolus Insulin Dose
timeFrame: Day 1, Days 1 to 11, Days 2 to 11, each individual day 2 to 11 of each period
measure: CGM Mean Absolute Relative Differences (MARD) Versus Time-stamped Blood Glucose (BG) Values From Meter Downloads
timeFrame: 11 days
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH) Diabetes Research Center
state: Massachusetts
city: Worcester
country: United States
facility: UMass Medical Center
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina Chapel Hill
state: North Carolina
Study officials:
affiliation: Massachusetts General Hospital
name: Steven J Russell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: El-Khatib FH, Balliro C, Hillard MA, Magyar KL, Ekhlaspour L, Sinha M, Mondesir D, Esmaeili A, Hartigan C, Thompson MJ, Malkani S, Lock JP, Harlan DM, Clinton P, Frank E, Wilson DM, DeSalvo D, Norlander L, Ly T, Buckingham BA, Diner J, Dezube M, Young LA, Goley A, Kirkman MS, Buse JB, Zheng H, Selagamsetty RR, Damiano ER, Russell SJ. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial. Lancet. 2017 Jan 28;389(10067):369-380. doi: 10.1016/S0140-6736(16)32567-3. Epub 2016 Dec 20.