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The Set-Point Study: Evaluating Effects of Changing Glucose Target on Bionic Pancreas Performance

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Steven J. Russell, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT02509065
First received: July 22, 2015
Last updated: January 13, 2017
Last verified: January 2017
  Purpose
The current study is designed to determine the effect on mean glucose, hypoglycemia, glucagon usage, and insulin usage of adjusting upward the glucose target of the bi-hormonal bionic pancreas, and determine whether there is a target at which adequate glycemic control is achieved by an insulin-only bionic pancreas with minimal hypoglycemia.

Condition Intervention Phase
Type 1 Diabetes
Device: Bionic Pancreas
Other: Usual Care
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Set-Point Study: Evaluating Effects of Changing Glucose Target on Bionic Pancreas Performance

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Mean CGM glucose values [ Time Frame: Days 2-3 ]
  • Fraction of time with CGM < 60 mg/dl [ Time Frame: Days 2-3 ]
  • Number of subjects discordant for reaching a BG < 60 mg/dl for > 2 consecutive plasma glucose measurements during inpatient exercise visit [ Time Frame: Day 4 ]
    During both 130 mg/dl arms, subjects will report for a fasted in-clinic exercise visit, with plasma blood glucose measurements obtained at least every 10 minutes


Secondary Outcome Measures:
  • Mean CGM glucose [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Fraction of time spent in: < 50 mg/dl, < 60 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Correlation between the bionic pancreas target and the mean CGM glucose [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Correlation between the bionic pancreas target and time < 60 mg/dl [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Percentage of subjects with mean CGM < 154 mg/dl [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Number of hypoglycemic events (< 70 mg/dl, <60 mg/dl, <50 mg/dl) [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    A series of hypoglycemic measurements is defined as a single event until there is a break of >/= 30 minutes between hypoglycemic measurements below the defined threshold

  • Area between the glucose curve and 60 mg/dl calculated from BG measurements [ Time Frame: Day 4 ]
  • Area between the glucose curve and 60 mg/dl calculated from CGM measurements [ Time Frame: Day 4 ]
  • Time from start of exercise to first BG measurement < 60 mg/dl [ Time Frame: Day 4 ]
  • Time from start of exercise to first CGM measurement < 60 mg/dl [ Time Frame: Day 4 ]
  • Fraction of days that CGM was used by participants as part of their usual care [ Time Frame: Days 1-3 ]
  • Number of severe hypoglycemic events [ Time Frame: Days 1-3 ]
    Subject unable to self-treat, requiring the assistance of another person

  • Glucagon total daily dose in bi-hormonal bionic pancreas arm [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Insulin total daily dose [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Correlation between bionic pancreas target and mean insulin dosing by the bionic pancreas [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Correlation between bionic pancreas target and mean glucagon dosing by the bionic pancreas [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Number of episodes of symptomatic hypoglycemia (reported daily by subjects) [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Number of reported carbohydrate interventions for hypoglycemia (reported daily by subjects) [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Total grams of carbohydrate taken for hypoglycemia [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Fraction of time bionic pancreas off-line or not functioning properly [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    e.g. due to system crash, communication problem between CGM and bionic pancreas, communication problem between bionic pancreas and pumps and pump malfunction

  • Grams of oral carbohydrates given to the subject to treat hypoglycemia [ Time Frame: Day 4 ]
  • Total glucagon dosing by bi-hormonal bionic pancreas from the start of exercise until the end of the visit [ Time Frame: Day 4 ]
  • Episodes of nausea and nausea index [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    sum of number of episodes times severity from VAS

  • Change in body weight [ Time Frame: From day 1 to day 4 of each arm ]
  • Any skin rash, either local to infusion sites or more generalized with subject reported severity and timing [ Time Frame: Days 1-3 ]

Other Outcome Measures:
  • Reliability index of CGM [ Time Frame: Days 1-3 ]
    Calculated as percent of possible values actually recorded by CGM

  • Correlation between mean CGM glucose and mean number of meal announcements per day [ Time Frame: Days 1-3 ]
  • Mean CGM glucose at the time of user-initiated glucagon doses [ Time Frame: Days 1-3 ]
  • Mean Absolute Relative Difference (%) between CGM glucose values and meter blood glucose values [ Time Frame: Days 1-3 ]
  • Mean number of daily BG measurements [ Time Frame: Days 1-3 ]
    From meter download

  • Number of hypoglycemic events as determined from all BG measurements < 70 mg/dl, < 60 mg/dl and < 50 mg/dl [ Time Frame: Days 1-3 ]
    A series of hypoglycemic measurements is defined as a single event until there is a break of >/= 30 minutes between hypoglycemic measurements

  • Fraction of subjects using a GLP-1 agonist during usual care [ Time Frame: Days 1-3 ]
  • Fraction of subjects using pramlintide during usual care [ Time Frame: Days 1-3 ]
  • Number of user initiated glucagon doses [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Fraction of user initiated glucagon doses followed within 15 minutes by a period of CGM connection loss [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    (i.e. when the feature was used as intended)

  • Correlation between the number of user initiated glucagon doses and number of reported carbohydrate interventions for hypoglycemia [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    reported daily by subjects

  • Correlation between the number of user initiated glucagon doses and total grams of carbohydrates taken for hypoglycemia [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    reported daily by subjects

  • Mean daily basal insulin dose [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Mean daily bolus insulin dose [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Correlation between number of user initiated glucagon doses and insulin dosing by the bionic pancreas [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Fraction of time bionic pancreas disconnected by the subject for bathing or swimming [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    by self-report

  • Number of unscheduled infusion set replacements [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Number of unscheduled CGM sensor changes [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Time without CGM monitoring data during the usual care arm [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • List of technical faults associated with the bionic pancreas including cause and resolution [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Alcohol intake [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    mean drinks per day

  • Percentage of time with CGM glucose <60 mg/dl in periods following alcohol intake vs. the matched periods on days without alcohol intake [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    Period starts with first drink and extends two hours after the last drink - if a new drink is consumed before the end of the 2-hour period, the period is extended until 2 hours after the last drink

  • Percentage of time with CGM glucose <60 mg/dl on nights following days with alcohol intake vs nights following days without alcohol intake [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Correlation between mean alcohol intake and percentage of time with CGM glucose <60 mg/dl per subject [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Exercise duration [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Exercise exposure [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
    duration x intensity

  • Percentage of time with CGM glucose <60 mg/dl in the nights following bouts of exercise vs. nights without exercise the preceding day [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]
  • Correlation between exercise exposure and percentage of time with CGM glucose <60 mg/dl [ Time Frame: Day 1, 2-3 and each individual day 2-3 ]

Estimated Enrollment: 80
Study Start Date: August 2015
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Usual Care
Comparator week to all closed-loop control, utilizing usual diabetes care and the subject's own insulin pump.
Other: Usual Care
Participant cares for their diabetes according to their usual practice, with blinded CGM monitoring. No medication will be administered by the study in this intervention.
Experimental: 145 mg/dl Set Point - insulin only
Automated blood glucose control via a closed-loop bionic pancreas device targeting a blood glucose level of 145 mg/dl and using only an insulin pump
Device: Bionic Pancreas
Participant wears the bionic pancreas, including an insulin and/or glucagon pump depending on which arm they are in. The 100 mg/dl arm will deliver insulin and glucagon. The 115 mg/dl arm will deliver insulin and glucagon. The 145 mg/dl arm will deliver just insulin. The 130 mg/dl arms will deliver insulin and placebo, or insulin and glucagon, and will be double blinded.
Experimental: 130 mg/dl Set Point - insulin only
Automated blood glucose control via a closed-loop bionic pancreas device targeting a blood glucose level of 130 mg/dl and using only an insulin pump
Device: Bionic Pancreas
Participant wears the bionic pancreas, including an insulin and/or glucagon pump depending on which arm they are in. The 100 mg/dl arm will deliver insulin and glucagon. The 115 mg/dl arm will deliver insulin and glucagon. The 145 mg/dl arm will deliver just insulin. The 130 mg/dl arms will deliver insulin and placebo, or insulin and glucagon, and will be double blinded.
Experimental: 130 mg/dl Set Point - bihormonal
Automated blood glucose control via a closed-loop bionic pancreas device targeting a blood glucose level of 130 mg/dl using both an insulin and a glucagon pump
Device: Bionic Pancreas
Participant wears the bionic pancreas, including an insulin and/or glucagon pump depending on which arm they are in. The 100 mg/dl arm will deliver insulin and glucagon. The 115 mg/dl arm will deliver insulin and glucagon. The 145 mg/dl arm will deliver just insulin. The 130 mg/dl arms will deliver insulin and placebo, or insulin and glucagon, and will be double blinded.
Experimental: 115 mg/dl Set Point - bihormonal
Automated blood glucose control via a closed-loop bionic pancreas device targeting a blood glucose level of 115 mg/dl using both an insulin and a glucagon pump
Device: Bionic Pancreas
Participant wears the bionic pancreas, including an insulin and/or glucagon pump depending on which arm they are in. The 100 mg/dl arm will deliver insulin and glucagon. The 115 mg/dl arm will deliver insulin and glucagon. The 145 mg/dl arm will deliver just insulin. The 130 mg/dl arms will deliver insulin and placebo, or insulin and glucagon, and will be double blinded.
Experimental: 100 mg/dl Set Point - bihormonal
Automated blood glucose control via a closed-loop bionic pancreas device targeting a blood glucose level of 100 mg/dl using both an insulin and a glucagon pump
Device: Bionic Pancreas
Participant wears the bionic pancreas, including an insulin and/or glucagon pump depending on which arm they are in. The 100 mg/dl arm will deliver insulin and glucagon. The 115 mg/dl arm will deliver insulin and glucagon. The 145 mg/dl arm will deliver just insulin. The 130 mg/dl arms will deliver insulin and placebo, or insulin and glucagon, and will be double blinded.

  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 judgment of the principal investigator)
  • Live within a 60 minute drive-time radius of the central monitoring location
  • Willing to remain within a 120 minute drive-time radius of the central monitoring location throughout the study
  • 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 one CGM sensor and change sets frequently (at least one new glucagon infusion set daily during bi-hormonal arms, and insulin infusion set every other day throughout the study)

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 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 (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:

oEpisodic or treatment refractory (requiring 4 or more medications to achieve normotension) hypertension oParoxysms of tachycardia, pallor, or headache oPersonal 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 within the last 2 years, 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 of 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 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: NCT02509065

Contacts
Contact: Courtney A Balliro, BS, RN, CDE 617-726-1242 cballiro@partners.org

Locations
United States, Massachusetts
Masscahusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Courtney A Balliro, BS, RN, CDE       cballiro@partners.org   
Contact: Michele Maheno, BSN, RN       mmaheno1@partners.org   
Principal Investigator: Steven J Russell, MD, PhD         
Sub-Investigator: Laya Ekhlaspour, MD         
Sub-Investigator: Courtney A Balliro, BS, RN         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Steven J Russell, MD, PhD Massachusetts General Hospital
  More Information

Additional Information:
Responsible Party: Steven J. Russell, MD, PhD, Assistant Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02509065     History of Changes
Other Study ID Numbers: 2015P001260
Study First Received: July 22, 2015
Last Updated: January 13, 2017

Keywords provided by Massachusetts General Hospital:
bionic pancreas
artificial pancreas
insulin
glucagon
continuous glucose monitor (CGM)
insulin pump
outpatient

Additional relevant MeSH terms:
Pancrelipase
Pancreatin
Glucagon-Like Peptide 1
Insulin, Globin Zinc
Insulin
Glucagon
Hypoglycemic Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Incretins

ClinicalTrials.gov processed this record on May 22, 2017