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A Multicenter Study of Outpatient Automated Blood Glucose Control With a Bihormonal Bionic Pancreas

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Boston University
Information provided by (Responsible Party):
Steven J. Russell, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT02092220
First received: March 18, 2014
Last updated: October 31, 2016
Last verified: October 2016
  Purpose

This study will test the hypothesis that a wearable bionic pancreas system that automatically delivers insulin and glucagon can provide superior regulation of glycemia vs. 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.


Condition Intervention Phase
Diabetes Mellitus Type 1
Device: Bionic Pancreas
Device: Patient controlled insulin pump
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Study of Outpatient Automated Blood Glucose Control With a Bihormonal Bionic Pancreas

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Mean CGMG during days 2-11 [ Time Frame: 10 days ]
    Co-primary outcome

  • Fraction of time spent with CGMG < 60 mg/dl during days 2-11 [ Time Frame: 10 days ]
    Co-primary outcome


Secondary Outcome Measures:
  • Mean CGMG [ Time Frame: day 1, days 2-11, days 1-11 ]
  • CGMG time in ranges [ Time Frame: day 1, days 2-11, days 1-11 ]
    < 50 mg/dl < 60 mg/dl < 70 mg/dl 70-120 mg/dl 70-180 mg/dl >250 mg/dl

  • Subjects with mean CGMG < 154 mg/dl [ Time Frame: day 1, days 2-11, days 1-11 ]
  • Number of hypoglycemic event [ Time Frame: day 1, days 2-11, days 1-11 ]
    < 70 mg/dl, < 60 mg/dl, <50 mg/dl; a series of hypoglycemic measurements is defined as a single event until there is a break of ≥ 30 minutes between measurements below the defined threshold

  • Fraction of days that CGM was used by participants as part of their usual care [ Time Frame: days 1-11 ]
  • Glycated albumin on day 11 [ Time Frame: 11 days ]
  • 1,5-anhydroglucitol on day 11 [ Time Frame: 11 days ]
  • Number of severe hypoglycemic events [ Time Frame: 11 days ]
    Subject unable to self-treat, requiring the assistance of another person

  • Number of episodes of symptomatic hypoglycemia [ Time Frame: day 1, days 2-11, days 1-11, overall, daytime, nighttime ]
  • Number of carbohydrate interventions for hypoglycemia [ Time Frame: day 1, days 2-11, days 1-11, overall, daytime, nighttime ]
  • Total grams of carbohydrate taken for hypoglycemia [ Time Frame: day 1, days 2-11, days 1-11, overall, daytime, nighttime ]
  • Insulin total daily dose [ Time Frame: day 1, days 2-11, days 1-11 ]
  • Glucagon total daily dose [ Time Frame: day 1, days 2-11, days 1-11 ]
  • Mean glucose target set by user (time-weighted average over study period) [ Time Frame: day 1, days 2-11, days 1-11, overall, daytime, nighttime ]
    time-weighted average over study period

  • Fraction of time bionic pancreas off-line or not functioning properly [ Time Frame: 11 days ]
  • Episodes of nausea and nausea index [ Time Frame: day 1, days 2-11, days 1-11, and each individual day ]
    Nausea index: sum of number of episodes times severity from VAS on

  • Change in body weight [ Time Frame: 11 days ]
  • Change in hemoglobin [ Time Frame: 11 days ]
  • Incidence of skin rash [ Time Frame: 11 days ]

Other Outcome Measures:
  • Reliability index, calculated as percent of possible values actually recorded by CGM [ Time Frame: 11 days ]
  • Correlation between mean CGMG and mean bionic pancreas target (100-130 mg/dl). [ Time Frame: 11 days, each individual day ]
  • Correlation between mean CGMG and mean number of meal announcements per day. [ Time Frame: 11 days ]
  • Mean CGM glucose at the time of user initiated glucagon doses. [ Time Frame: 11 days ]
  • CGM MARD versus time-stamped BG values from meter downloads. [ Time Frame: 11 days ]
  • Mean number of daily BG measurements. [ Time Frame: 11 days ]
  • Number of hypoglycemic events from all BG measurements. [ Time Frame: 11 days ]
    < 70 mg/dl < 60 mg/dl, and < 50 mg/dl; a series of hypoglycemic measurements is defined as a single event until there is a break of ≥ 30 minutes between hypoglycemic measurements

  • Correlation of glycated albumin with mean CGMG. [ Time Frame: Day 11 ]
  • Correlation of glycated albumin with mean BG from meter download. [ Time Frame: Day 11 ]
  • Change in glycated albumin. [ Time Frame: Day 1-11 ]
  • Correlation of 1,5-anhydroglucitol with CGMG time >180 mg/dL. [ Time Frame: 11 days ]
    Day 11 1,5-anhydro with CGM time > 180 mg/dl on days 1-11

  • Change in 1,5-anhydroglucitol. [ Time Frame: Day 1-11 ]
  • Fraction of subjects using a GLP-1 agonist during usual care. [ Time Frame: 11 days ]
  • Fraction of subjects using pramlintide during usual care. [ Time Frame: 11 days ]
  • Number of user initiated glucagon doses. [ Time Frame: 11 days ]
  • Fraction of user initiated glucagon doses followed within 15 minutes by a period of CGM connection loss. [ Time Frame: 11 days ]
  • Correlation between the number of user initiated glucagon doses and number of reported carbohydrate interventions for hypoglycemia. [ Time Frame: 11 days ]
  • Correlation between the number of user initiated glucagon doses and total grams of carbohydrate taken for hypoglycemia. [ Time Frame: 11 days ]
  • Mean daily basal insulin dose. [ Time Frame: 11 days ]
  • Mean daily bolus insulin dose. [ Time Frame: Day 1, days 2-11, each individual day 2-11 ]
  • Correlation between mean bionic pancreas target (100 -130 mg/dl) and mean insulin dosing by the bionic pancreas. [ Time Frame: Day 1, days 2-11, each individual day 2-11 ]
  • Correlation between mean bionic pancreas target (100 -130 mg/dl) and mean glucagon dosing by the bionic pancreas. [ Time Frame: Day 1, days 2-11, each individual day 2-11 ]
  • Correlation between number of user initiated glucagon doses and insulin dosing by the bionic pancreas. [ Time Frame: Day 1, days 2-11, each individual day 2-11 ]
  • Correlation between number of user initiated glucagon doses and overall glucagon dosing by the bionic pancreas. [ Time Frame: Day 1, days 2-11, each individual day 2-11 ]
  • Daily mean of glucose targets set by users. [ Time Frame: Day 1, days 2-11, each individual day 2-11 ]
  • Number of times temporary glucose target feature used. [ Time Frame: Day 1, days 2-11, each individual day 2-11 ]
  • Mean target glucose during subjects self-reported sleep time and awake time. [ Time Frame: 11 days ]
  • Fraction of time bionic pancreas disconnected by the subject for bathing or swimming. [ Time Frame: 11 days ]
  • Number of unscheduled infusion set replacements. [ Time Frame: 11 days ]
  • Number of unscheduled CGM sensor changes. [ Time Frame: 11 days ]
  • Time without CGM monitoring data during the usual care arm. [ Time Frame: 11 days ]
  • Change in the mean of any parameter of the complete blood count. [ Time Frame: 11 days ]
  • Number of subjects with change of any parameter of the complete blood count from normal to abnormal. [ Time Frame: 11 days ]
  • Change in the mean of any parameter of the blood chemistry panel. [ Time Frame: 11 days ]
  • Number of subjects with change of any parameter of the blood chemistry panel from normal to abnormal . [ Time Frame: 11 days ]
  • Episodes of reported diarrhea with subject reported severity and timing. [ Time Frame: 11 days ]

Estimated Enrollment: 48
Study Start Date: April 2014
Estimated Study Completion Date: December 2016
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bionic Pancreas
Bionic Pancreas Diabetes Management
Device: Bionic Pancreas
Active Comparator: Usual Care
Usual Care Diabetes Management
Device: Patient controlled insulin pump

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 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 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 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 (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 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
  • 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, DPP-4 inhibitors, 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02092220

Locations
United States, Massachusetts
MGH Diabetes Research Center
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Boston University
Investigators
Principal Investigator: Steven J Russell, MD, PhD Massachusetts General Hospital
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Steven J. Russell, MD, PhD, Assistant Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02092220     History of Changes
Other Study ID Numbers: Multicenter Study
Study First Received: March 18, 2014
Last Updated: October 31, 2016

Keywords provided by Massachusetts General Hospital:
Bionic Pancreas
Insulin
Glucagon
Continuous Glucose Monitor

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Pancrelipase
Pancreatin
Hypoglycemic Agents
Physiological Effects of Drugs
Gastrointestinal Agents

ClinicalTrials.gov processed this record on March 24, 2017