Type 1 Diabetes, Type 2 Diabetes
Conditions
Keywords
bionic pancreas, artificial pancreas, insulin, glucagon, continuous glucose monitor (CGM), insulin pump, outpatient
Brief summary
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.
Detailed description
We have two specific aims: Aim 1 is to conduct an outpatient study testing multiple configurations of the bionic pancreas in 24 adult subjects with type 1 diabetes in a random cross-over study versus usual care with an insulin pump. These bionic pancreas configurations include the insulin only BP at 145 mg/dl set point, 130 mg/dl set point, 120 mg/dl set point and 110 mg/dl set point and the bihormonal BP at 130 mg/dl set point, 115 mg/dl set point and 110 mg/dl set point. These arms are all compared to usual care. Aim 2 is to evaluate the incremental utility of glucagon in the context of automated insulin delivery by the bionic pancreas in preventing hypoglycemia during exercise in the fasted state. The 130 mg/dl set points and 110 mg/dl set points also participate in this fasted exercise visit. These two set points are double blinded, so neither the subjects nor the study staff are aware which arm is bihormonal and which arm is insulin only.
Interventions
DEVICEBionic 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 for type 1 diabetes patients will deliver insulin and glucagon. The 100 mg/dl arm for type 2 diabetes patients will deliver just insulin. The 115 mg/dl arm will deliver insulin and glucagon. The 120 mg/dl arm will deliver just insulin. The 145 mg/dl arm will deliver just insulin. The 130 mg/dl and 110 mg/dl arms will deliver insulin and placebo, or insulin and glucagon, and will be double blinded.
OTHERUsual 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.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
Some of the study arms are double blinded: the 110 mg/dl and 130 mg/dl set point configurations of the bionic pancreas are double blinded, so neither the patient nor the study team know if they are using the bihormonal bionic pancreas or insulin only bionic pancreas
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Type 1 Diabetes Subjects: Age ≥ 18 years and have had clinical type 1 diabetes for at least one year, and managed using an insulin pump for ≥ 6 months Type 2 Diabetes subjects: Age ≥ 18 years and have type 2 diabetes managed with rapid acting insulin in an insulin pump, or multiple daily injections including both long acting and short acting insulin * 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) * Have a mobile phone they are willing to keep with them and answer calls from study staff
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 * Type 1 diabetes subjects: Use of oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, DPP-4 inhibitors, SGLT-2 inhibitors) anti-diabetic medications * Type 2 diabetes subjects: Use of oral anti-diabetic medications other than metformin * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Continuous Glucose Monitor (CGM) Glucose Values | Days 2 and 3 | Glucose values were collected from the Dexcom G4 CGM device every 5 minutes and an average (calculated mean with associated standard deviation) CGM glucose level (mg/dl) was calculated from days 2 and 3 of the study arm. |
| Percentage of Time With CGM < 60 mg/dl | Days 2 and 3 | For this calculation we analyzed data from every 5 minutes of CGM data for days 2 and 3 of each study arm. We looked specifically at the percentage time of those roughly 48 hours that had any glucose values less than 60 mg/dl. The final value presented is the percent of time per 2 days of the study arm spent in a specific hypoglycemia range of less than 60 mg/dl with an associated standard deviation. |
| Number of Subjects Discordant for Reaching a BG < 60 mg/dl for > 2 Consecutive Plasma Glucose Measurements During Inpatient Exercise Visit | Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only) | During both 110 mg/dl and 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Mean CGM < 154 mg/dl | Days 2-3 | The percentage of subjects who's mean CGM glucose level is \< 154 mg/dl, which is an estimated hemoglobin a1c \< 7%, which is the ADA goal for therapy |
| Area Between the Glucose Curve and 60 mg/dl Calculated From BG Measurements | Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only) | Plasma glucose values to create this curve included time points from time 0 to a maximum of 360 minutes, with a sampling frequency of at least every 10 minutes throughout. |
| Area Between the Glucose Curve and 60 mg/dl Calculated From CGM Measurements | Day 4 in-clinic Exercise Visit (type 1 diabetes only, 110 and 130 mg/dl arms only) | CGM glucose values to create this curve included time points from time 0 to a maximum of 360 minutes, with a sampling frequency of every 5 minutes |
| Mean CGM Glucose | Days 1 through 3 | Average glucose according to continuous glucose monitor readings including the 1 day washout |
| Time From Start of Exercise to First CGM Measurement < 60 mg/dl | Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only) | During both 110 mg/dl and 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 |
| Grams of Carbohydrates Given to the Subject to Treat Hypoglycemia | Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only) | During both 110 mg/dl and 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 |
| Total Glucagon Dosing by the Bihormonal Bionic Pancreas From the Start of Exercise Until the End of the Visit | Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only) | During both 110 mg/dl and 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 |
| Time From Start of Exercise to First BG Measurement < 60 mg/dl | Day 4 in-clinic Exercise Visit (type 1 diabetes only, 110 and 130 mg/dl arms only) | During both 110 mg/dl and 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 |
| Nausea Severity | Days 1-3 | The average severity of nausea, as recorded on a 10 centimeter visual analog scale by the daily e-mail survey they receive. Scores were determined by how many centimeters the subject marked as a surrogate for their nausea level on a daily basis. Any value more than 0 cm indicates some degree of nausea with a score of 10 cm being the worst nausea imaginable. A score less than 3 cm indicates a mild level of nausea. |
| Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | Days 2-3 | The fraction of time spent in each of these ranges according to continuous glucose monitor readings |
Countries
United States
Participant flow
Recruitment details
27 subjects were recruited and found eligible. Of the 27, only 24 subjects participated in the trial.
Pre-assignment details
There were 24 subjects and a total of 9 study arms.The order of the arms was assigned in a psuedo random cross-over design. The 110 and 120 mg/dl arms were added later and were not included in the original randomization. 11 of the same subjects completed all 9 arms. Each arm had 20 subjects total, but these 20 were not the same cohort in each arm.
Participants by arm
| Arm | Count |
|---|---|
| All Enrolled Subjects All subjects enrolled into the study | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | All Enrolled Subjects |
|---|---|
| Age, Continuous | 38.6 years STANDARD_DEVIATION 15.5 |
| Hemoglobin A1c | 7.3 percent STANDARD_DEVIATION 0.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Mean Continuous Glucose Monitor (CGM) Glucose Values
Glucose values were collected from the Dexcom G4 CGM device every 5 minutes and an average (calculated mean with associated standard deviation) CGM glucose level (mg/dl) was calculated from days 2 and 3 of the study arm.
Time frame: Days 2 and 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Mean Continuous Glucose Monitor (CGM) Glucose Values | 158 mg/dl | Standard Deviation 31 |
| 145 mg/dl Set Point - Insulin Only | Mean Continuous Glucose Monitor (CGM) Glucose Values | 174 mg/dl | Standard Deviation 23 |
| 130 mg/dl Set Point - Insulin Only | Mean Continuous Glucose Monitor (CGM) Glucose Values | 161 mg/dl | Standard Deviation 17 |
| 130 mg/dl Set Point - Bihormonal | Mean Continuous Glucose Monitor (CGM) Glucose Values | 156 mg/dl | Standard Deviation 12 |
| 115 mg/dl Set Point - Bihormonal | Mean Continuous Glucose Monitor (CGM) Glucose Values | 146 mg/dl | Standard Deviation 15 |
| 100 mg/dl Set Point - Bihormonal | Mean Continuous Glucose Monitor (CGM) Glucose Values | 136 mg/dl | Standard Deviation 14 |
| 110 mg/dl Set Point - Insulin Only | Mean Continuous Glucose Monitor (CGM) Glucose Values | 153 mg/dl | Standard Deviation 15 |
| 110 mg/dl Set Point - Bihormonal | Mean Continuous Glucose Monitor (CGM) Glucose Values | 148 mg/dl | Standard Deviation 17 |
| 120 mg/dl Set Point - Insulin Only | Mean Continuous Glucose Monitor (CGM) Glucose Values | 156 mg/dl | Standard Deviation 15 |
Primary
Number of Subjects Discordant for Reaching a BG < 60 mg/dl for > 2 Consecutive Plasma Glucose Measurements During Inpatient Exercise Visit
During both 110 mg/dl and 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
Time frame: Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Number of Subjects Discordant for Reaching a BG < 60 mg/dl for > 2 Consecutive Plasma Glucose Measurements During Inpatient Exercise Visit | 0 Participants |
| 145 mg/dl Set Point - Insulin Only | Number of Subjects Discordant for Reaching a BG < 60 mg/dl for > 2 Consecutive Plasma Glucose Measurements During Inpatient Exercise Visit | 0 Participants |
| 130 mg/dl Set Point - Insulin Only | Number of Subjects Discordant for Reaching a BG < 60 mg/dl for > 2 Consecutive Plasma Glucose Measurements During Inpatient Exercise Visit | 3 Participants |
| 130 mg/dl Set Point - Bihormonal | Number of Subjects Discordant for Reaching a BG < 60 mg/dl for > 2 Consecutive Plasma Glucose Measurements During Inpatient Exercise Visit | 1 Participants |
Primary
Percentage of Time With CGM < 60 mg/dl
For this calculation we analyzed data from every 5 minutes of CGM data for days 2 and 3 of each study arm. We looked specifically at the percentage time of those roughly 48 hours that had any glucose values less than 60 mg/dl. The final value presented is the percent of time per 2 days of the study arm spent in a specific hypoglycemia range of less than 60 mg/dl with an associated standard deviation.
Time frame: Days 2 and 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Percentage of Time With CGM < 60 mg/dl | 1.38 percentage of time | Standard Deviation 2.6 |
| 145 mg/dl Set Point - Insulin Only | Percentage of Time With CGM < 60 mg/dl | 0.96 percentage of time | Standard Deviation 1.5 |
| 130 mg/dl Set Point - Insulin Only | Percentage of Time With CGM < 60 mg/dl | 0.79 percentage of time | Standard Deviation 1.4 |
| 130 mg/dl Set Point - Bihormonal | Percentage of Time With CGM < 60 mg/dl | 0.55 percentage of time | Standard Deviation 1 |
| 115 mg/dl Set Point - Bihormonal | Percentage of Time With CGM < 60 mg/dl | 0.88 percentage of time | Standard Deviation 1.2 |
| 100 mg/dl Set Point - Bihormonal | Percentage of Time With CGM < 60 mg/dl | 0.76 percentage of time | Standard Deviation 1.1 |
| 110 mg/dl Set Point - Insulin Only | Percentage of Time With CGM < 60 mg/dl | 1.34 percentage of time | Standard Deviation 1.3 |
| 110 mg/dl Set Point - Bihormonal | Percentage of Time With CGM < 60 mg/dl | 0.4 percentage of time | Standard Deviation 0.6 |
| 120 mg/dl Set Point - Insulin Only | Percentage of Time With CGM < 60 mg/dl | 1.05 percentage of time | Standard Deviation 1.7 |
Secondary
Area Between the Glucose Curve and 60 mg/dl Calculated From BG Measurements
Plasma glucose values to create this curve included time points from time 0 to a maximum of 360 minutes, with a sampling frequency of at least every 10 minutes throughout.
Time frame: Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Area Between the Glucose Curve and 60 mg/dl Calculated From BG Measurements | 0 min*mg/dl | Standard Deviation 0 |
| 145 mg/dl Set Point - Insulin Only | Area Between the Glucose Curve and 60 mg/dl Calculated From BG Measurements | 0 min*mg/dl | Standard Deviation 0 |
| 130 mg/dl Set Point - Insulin Only | Area Between the Glucose Curve and 60 mg/dl Calculated From BG Measurements | 26.3 min*mg/dl | Standard Deviation 78.5 |
| 130 mg/dl Set Point - Bihormonal | Area Between the Glucose Curve and 60 mg/dl Calculated From BG Measurements | 5.15 min*mg/dl | Standard Deviation 23.03 |
Secondary
Area Between the Glucose Curve and 60 mg/dl Calculated From CGM Measurements
CGM glucose values to create this curve included time points from time 0 to a maximum of 360 minutes, with a sampling frequency of every 5 minutes
Time frame: Day 4 in-clinic Exercise Visit (type 1 diabetes only, 110 and 130 mg/dl arms only)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Area Between the Glucose Curve and 60 mg/dl Calculated From CGM Measurements | 14.8 min*mg/dl | Standard Deviation 66.2 |
| 145 mg/dl Set Point - Insulin Only | Area Between the Glucose Curve and 60 mg/dl Calculated From CGM Measurements | 0 min*mg/dl | Standard Deviation 0 |
| 130 mg/dl Set Point - Insulin Only | Area Between the Glucose Curve and 60 mg/dl Calculated From CGM Measurements | 29.6 min*mg/dl | Standard Deviation 91.5 |
| 130 mg/dl Set Point - Bihormonal | Area Between the Glucose Curve and 60 mg/dl Calculated From CGM Measurements | 0 min*mg/dl | Standard Deviation 0 |
Secondary
Grams of Carbohydrates Given to the Subject to Treat Hypoglycemia
During both 110 mg/dl and 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
Time frame: Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Grams of Carbohydrates Given to the Subject to Treat Hypoglycemia | 0 grams of carbohydrates | Standard Deviation 0 |
| 145 mg/dl Set Point - Insulin Only | Grams of Carbohydrates Given to the Subject to Treat Hypoglycemia | 0 grams of carbohydrates | Standard Deviation 0 |
| 130 mg/dl Set Point - Insulin Only | Grams of Carbohydrates Given to the Subject to Treat Hypoglycemia | 1.77 grams of carbohydrates | Standard Deviation 5.51 |
| 130 mg/dl Set Point - Bihormonal | Grams of Carbohydrates Given to the Subject to Treat Hypoglycemia | 0.86 grams of carbohydrates | Standard Deviation 3.83 |
Secondary
Mean CGM Glucose
Average glucose according to continuous glucose monitor readings including the 1 day washout
Time frame: Days 1 through 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Mean CGM Glucose | 160.8 mg/dl | Standard Deviation 30.4 |
| 145 mg/dl Set Point - Insulin Only | Mean CGM Glucose | 177.8 mg/dl | Standard Deviation 19.5 |
| 130 mg/dl Set Point - Insulin Only | Mean CGM Glucose | 164.1 mg/dl | Standard Deviation 15.3 |
| 130 mg/dl Set Point - Bihormonal | Mean CGM Glucose | 159.4 mg/dl | Standard Deviation 13.4 |
| 115 mg/dl Set Point - Bihormonal | Mean CGM Glucose | 151.6 mg/dl | Standard Deviation 16.1 |
| 100 mg/dl Set Point - Bihormonal | Mean CGM Glucose | 140.7 mg/dl | Standard Deviation 15.4 |
| 110 mg/dl Set Point - Insulin Only | Mean CGM Glucose | 158.8 mg/dl | Standard Deviation 18.4 |
| 110 mg/dl Set Point - Bihormonal | Mean CGM Glucose | 155.0 mg/dl | Standard Deviation 19.4 |
| 120 mg/dl Set Point - Insulin Only | Mean CGM Glucose | 160.2 mg/dl | Standard Deviation 18.9 |
Secondary
Nausea Severity
The average severity of nausea, as recorded on a 10 centimeter visual analog scale by the daily e-mail survey they receive. Scores were determined by how many centimeters the subject marked as a surrogate for their nausea level on a daily basis. Any value more than 0 cm indicates some degree of nausea with a score of 10 cm being the worst nausea imaginable. A score less than 3 cm indicates a mild level of nausea.
Time frame: Days 1-3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Nausea Severity | 0.3 scores on a scale 0-10 cm | Standard Deviation 0.5 |
| 145 mg/dl Set Point - Insulin Only | Nausea Severity | 0.5 scores on a scale 0-10 cm | Standard Deviation 1.6 |
| 130 mg/dl Set Point - Insulin Only | Nausea Severity | 0.4 scores on a scale 0-10 cm | Standard Deviation 0.6 |
| 130 mg/dl Set Point - Bihormonal | Nausea Severity | 0.4 scores on a scale 0-10 cm | Standard Deviation 0.6 |
| 115 mg/dl Set Point - Bihormonal | Nausea Severity | 0.8 scores on a scale 0-10 cm | Standard Deviation 1.6 |
| 100 mg/dl Set Point - Bihormonal | Nausea Severity | 1.2 scores on a scale 0-10 cm | Standard Deviation 1.8 |
| 110 mg/dl Set Point - Insulin Only | Nausea Severity | 0.64 scores on a scale 0-10 cm | Standard Deviation 1.25 |
| 110 mg/dl Set Point - Bihormonal | Nausea Severity | 0.80 scores on a scale 0-10 cm | Standard Deviation 1.38 |
| 120 mg/dl Set Point - Insulin Only | Nausea Severity | 0.26 scores on a scale 0-10 cm | Standard Deviation 0.26 |
Secondary
Percentage of Subjects With Mean CGM < 154 mg/dl
The percentage of subjects who's mean CGM glucose level is \< 154 mg/dl, which is an estimated hemoglobin a1c \< 7%, which is the ADA goal for therapy
Time frame: Days 2-3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Percentage of Subjects With Mean CGM < 154 mg/dl | 7 Participants |
| 145 mg/dl Set Point - Insulin Only | Percentage of Subjects With Mean CGM < 154 mg/dl | 1 Participants |
| 130 mg/dl Set Point - Insulin Only | Percentage of Subjects With Mean CGM < 154 mg/dl | 7 Participants |
| 130 mg/dl Set Point - Bihormonal | Percentage of Subjects With Mean CGM < 154 mg/dl | 6 Participants |
| 115 mg/dl Set Point - Bihormonal | Percentage of Subjects With Mean CGM < 154 mg/dl | 16 Participants |
| 100 mg/dl Set Point - Bihormonal | Percentage of Subjects With Mean CGM < 154 mg/dl | 18 Participants |
| 110 mg/dl Set Point - Insulin Only | Percentage of Subjects With Mean CGM < 154 mg/dl | 12 Participants |
| 110 mg/dl Set Point - Bihormonal | Percentage of Subjects With Mean CGM < 154 mg/dl | 13 Participants |
| 120 mg/dl Set Point - Insulin Only | Percentage of Subjects With Mean CGM < 154 mg/dl | 5 Participants |
Secondary
Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl
The fraction of time spent in each of these ranges according to continuous glucose monitor readings
Time frame: Days 2-3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual Care | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-120 mg/dl | 29.3 percentage of time | Standard Deviation 18.8 |
| Usual Care | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 250 mg/dl | 8.2 percentage of time | Standard Deviation 8.4 |
| Usual Care | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 70 mg/dl | 3.8 percentage of time | Standard Deviation 6.2 |
| Usual Care | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 50 mg/dl | 0.3 percentage of time | Standard Deviation 0.6 |
| Usual Care | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 180 mg/dl | 33.7 percentage of time | Standard Deviation 21.5 |
| Usual Care | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-180 mg/dl | 62.5 percentage of time | Standard Deviation 19 |
| 145 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 250 mg/dl | 11.3 percentage of time | Standard Deviation 12 |
| 145 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 180 mg/dl | 40.6 percentage of time | Standard Deviation 40.9 |
| 145 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 70 mg/dl | 2.4 percentage of time | Standard Deviation 2.2 |
| 145 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-180 mg/dl | 57.0 percentage of time | Standard Deviation 11.2 |
| 145 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-120 mg/dl | 16.9 percentage of time | Standard Deviation 5.8 |
| 145 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 50 mg/dl | 0.5 percentage of time | Standard Deviation 1 |
| 130 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-120 mg/dl | 21.3 percentage of time | Standard Deviation 7.4 |
| 130 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 180 mg/dl | 30.5 percentage of time | Standard Deviation 13.1 |
| 130 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 250 mg/dl | 6.6 percentage of time | Standard Deviation 7.3 |
| 130 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-180 mg/dl | 67.2 percentage of time | Standard Deviation 13.6 |
| 130 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 50 mg/dl | 0.2 percentage of time | Standard Deviation 0.8 |
| 130 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 70 mg/dl | 2.3 percentage of time | Standard Deviation 2.1 |
| 130 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 70 mg/dl | 1.3 percentage of time | Standard Deviation 2 |
| 130 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 50 mg/dl | 0.1 percentage of time | Standard Deviation 0.3 |
| 130 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-120 mg/dl | 25.9 percentage of time | Standard Deviation 10.2 |
| 130 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-180 mg/dl | 70.8 percentage of time | Standard Deviation 10.2 |
| 130 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 180 mg/dl | 27.9 percentage of time | Standard Deviation 9.8 |
| 130 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 250 mg/dl | 5.1 percentage of time | Standard Deviation 3.8 |
| 115 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 50 mg/dl | 0.2 percentage of time | Standard Deviation 0.4 |
| 115 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 180 mg/dl | 21.6 percentage of time | Standard Deviation 10.3 |
| 115 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-120 mg/dl | 34.3 percentage of time | Standard Deviation 8.2 |
| 115 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-180 mg/dl | 76.1 percentage of time | Standard Deviation 11 |
| 115 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 250 mg/dl | 5.7 percentage of time | Standard Deviation 6.7 |
| 115 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 70 mg/dl | 2.3 percentage of time | Standard Deviation 2.3 |
| 100 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-180 mg/dl | 80.7 percentage of time | Standard Deviation 8.2 |
| 100 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 50 mg/dl | 0.2 percentage of time | Standard Deviation 0.7 |
| 100 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 180 mg/dl | 16.9 percentage of time | Standard Deviation 8.5 |
| 100 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 250 mg/dl | 3.4 percentage of time | Standard Deviation 4.5 |
| 100 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-120 mg/dl | 45.3 percentage of time | Standard Deviation 11.1 |
| 100 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 70 mg/dl | 2.4 percentage of time | Standard Deviation 2 |
| 110 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-120 mg/dl | 30.2 percentage of time | Standard Deviation 7.1 |
| 110 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 70 mg/dl | 3.6 percentage of time | Standard Deviation 2.2 |
| 110 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 250 mg/dl | 7.7 percentage of time | Standard Deviation 6.2 |
| 110 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-180 mg/dl | 70.4 percentage of time | Standard Deviation 10.3 |
| 110 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 180 mg/dl | 26.0 percentage of time | Standard Deviation 10.2 |
| 110 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 50 mg/dl | 0.5 percentage of time | Standard Deviation 0.7 |
| 110 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 180 mg/dl | 22.2 percentage of time | Standard Deviation 11.6 |
| 110 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-180 mg/dl | 76.5 percentage of time | Standard Deviation 11.2 |
| 110 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-120 mg/dl | 37.5 percentage of time | Standard Deviation 10.5 |
| 110 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 70 mg/dl | 1.2 percentage of time | Standard Deviation 1.3 |
| 110 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 250 mg/dl | 6.5 percentage of time | Standard Deviation 7 |
| 110 mg/dl Set Point - Bihormonal | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 50 mg/dl | 0.1 percentage of time | Standard Deviation 0.2 |
| 120 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 250 mg/dl | 5.6 percentage of time | Standard Deviation 6 |
| 120 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | > 180 mg/dl | 28.2 percentage of time | Standard Deviation 12.9 |
| 120 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 50 mg/dl | 0.3 percentage of time | Standard Deviation 0.6 |
| 120 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-180 mg/dl | 69.5 percentage of time | Standard Deviation 14 |
| 120 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | 70-120 mg/dl | 25.1 percentage of time | Standard Deviation 7.6 |
| 120 mg/dl Set Point - Insulin Only | Percentage of Time Spent in: < 50 mg/dl, < 70 mg/dl, 70-120 mg/dl, 70-180 mg/dl, > 180 mg/dl, >250 mg/dl | < 70 mg/dl | 2.4 percentage of time | Standard Deviation 3.3 |
Secondary
Time From Start of Exercise to First BG Measurement < 60 mg/dl
During both 110 mg/dl and 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
Time frame: Day 4 in-clinic Exercise Visit (type 1 diabetes only, 110 and 130 mg/dl arms only)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Time From Start of Exercise to First BG Measurement < 60 mg/dl | NA minutes | — |
| 145 mg/dl Set Point - Insulin Only | Time From Start of Exercise to First BG Measurement < 60 mg/dl | NA minutes | — |
| 130 mg/dl Set Point - Insulin Only | Time From Start of Exercise to First BG Measurement < 60 mg/dl | 46.7 minutes | Standard Deviation 59.2 |
| 130 mg/dl Set Point - Bihormonal | Time From Start of Exercise to First BG Measurement < 60 mg/dl | 30 minutes | Standard Deviation 0 |
Secondary
Time From Start of Exercise to First CGM Measurement < 60 mg/dl
During both 110 mg/dl and 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
Time frame: Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Time From Start of Exercise to First CGM Measurement < 60 mg/dl | 25.0 minutes | Standard Deviation 0 |
| 145 mg/dl Set Point - Insulin Only | Time From Start of Exercise to First CGM Measurement < 60 mg/dl | NA minutes | — |
| 130 mg/dl Set Point - Insulin Only | Time From Start of Exercise to First CGM Measurement < 60 mg/dl | 53.3 minutes | Standard Deviation 31.7 |
| 130 mg/dl Set Point - Bihormonal | Time From Start of Exercise to First CGM Measurement < 60 mg/dl | NA minutes | — |
Secondary
Total Glucagon Dosing by the Bihormonal Bionic Pancreas From the Start of Exercise Until the End of the Visit
During both 110 mg/dl and 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
Time frame: Day 4 in-clinic Exercise Visit (110 and 130 mg/dl arms only)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Total Glucagon Dosing by the Bihormonal Bionic Pancreas From the Start of Exercise Until the End of the Visit | 0.0 mcg/kg | Standard Deviation 0 |
| 145 mg/dl Set Point - Insulin Only | Total Glucagon Dosing by the Bihormonal Bionic Pancreas From the Start of Exercise Until the End of the Visit | 1.36 mcg/kg | Standard Deviation 1.06 |
| 130 mg/dl Set Point - Insulin Only | Total Glucagon Dosing by the Bihormonal Bionic Pancreas From the Start of Exercise Until the End of the Visit | 0.0 mcg/kg | Standard Deviation 0 |
| 130 mg/dl Set Point - Bihormonal | Total Glucagon Dosing by the Bihormonal Bionic Pancreas From the Start of Exercise Until the End of the Visit | 0.70 mcg/kg | Standard Deviation 0.53 |