Diabetes Mellitus
Conditions
Keywords
Closed-loop, Artificial pancreas, Bi-hormonal, Insulin, Glucagon, Diabetes mellitus type 1
Brief summary
The investigators hypothesize that our closed-loop glucose-control system can provide BG control in subjects with type 1 diabetes using the estimated BG signal from a CGM as the input signal to the controller.
Detailed description
To test the safety and efficacy of our control system in the bi-hormonal configuration in regulating BG in adults (18 years of age or older) and in children (12-17 years of age) with type 1 diabetes based on interstitial-fluid (ISF) glucose data from a CGM. Experiments will be 51 hours in length incorporating 6 meals and two (night) sleep periods. In order to evaluate the effect of exercise on BG control, the last 48 hours of the experiment will be divided into two 24 hour blocks, the second of which will contain a period of structured exercise near the beginning of the block.
Interventions
DEVICEBi-hormonal (insulin and glucagon) artificial pancreas
Subjects wore a bionic pancreas consisting of a continuous glucose monitor, an insulin pump and a glucagon pump
Sponsors
Massachusetts General Hospital
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Juvenile Diabetes Research Foundation
The Leona M. and Harry B. Helmsley Charitable Trust
Boston University Charles River Campus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 12 years or older with clinical type 1 diabetes for at least one year * Weight \> 41 kg * Otherwise healthy (mild chronic disease allowed if well controlled) * Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting insulins * Body mass index (BMI) between 20 and 35 for subjects \>18 years of age or BMI between the 5th and 95th percentile for age for subjects \< 18 years of age * Total daily dose (TDD) of insulin that is \< 1 U/kg * Stimulated C-peptide \< 0.1 nmol/L at 90 minutes after liquid mixed meal by DCCT protocol * Hemoglobin A1c \<= 9% * Prescription medication regimen stable for 1 month
Exclusion criteria
* Unable to provide informed consent for subjects \> 18 years of age or unable to provide assent if \< 18 years of age * Unable to comply with study procedures * Current participation in another diabetes-related clinical trial other than one that is primarily observational in nature. Potential subjects enrolled in trials of passive monitoring equipment are not excluded. * Anemia (HCT less than normal for age and sex) * Alanine aminotransferase \> 3 fold above upper limit of normal * Untreated or inadequately treated hyperthyroidism or hypothyroidism * Pregnancy * Renal insufficiency (creatinine clearance ≤ 50 ml/min) * Any known history of coronary artery disease * Abnormal EKG including, but not limited to evidence of active ischemia, prior myocardial infarction, proximal LAD critical stenosis (Wellen's sign), arrhythmia, tachycardia, and prolonged QT interval (\> 440 ms) * Congestive heart failure * History of TIA or stroke * Acute illness or exacerbation of chronic illness * History of seizures * History of pheochromocytoma (fractionated metanephrines will be tested in patients with history suggestive of pheochromocytoma) * History of adrenal disease or tumor * History of pancreatic tumor, including insulinoma * History of impaired gastric motility or gastroparesis requiring pharmacological or surgical treatment * Current alcohol abuse (intake averaging \> 3 drinks daily in last 30 days) or substance abuse (any use within the last 6 months of controlled substances without a prescription) * Untreated or inadequately treated mental illness (indicators would include symptoms such as psychosis, hallucinations, mania, and any psychiatric hospitalization in the last year) * Impaired cognition or altered mental status. * Hypertension (blood pressure \> 140/90 or \> 95% for age, height and weight in subjects \< 18 years of age) at the time of screening * Use of medications that reduce gastric motility (e.g. narcotics, anti-spasmodics, anticholinergics). * Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference * Use non-insulin, injectable anti-diabetic medications * History of adverse reaction to glucagon (including allergy) besides nausea and vomiting. * Established history of latex, adhesive, or tape allergy * Inadequate venous access * History of allergy to aspirin or any history of aspirin intolerance, including Reye syndrome, or gastric ulcer or bleeding associated with salicylates * Blood dyscrasia or bleeding diathesis, such as hemophilia, Von Willebrands disorder, and idiopathic thrombocytopenic purpura (ITP) * Peptic ulcer * Unable to perform 30 minutes of moderate exercise on a treadmill or exercise bicycle * Unable or unwilling to discontinue dietary supplements for at least 2 weeks prior to each CRC admission * History of celiac disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl) | 48 hours |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Time Spent With Blood Glucose <70 mg/dl | 48 hours |
| Percentage of Time Spent With Blood Glucose 70-180 mg/dl | 48 hours |
| Insulin Total Daily Dose | 48 hours |
| Percentage of Time Spent With Blood Glucose < 60 mg/dl | 48 hours |
| Number of Blood Glucose Events < 70 mg/dl | 48 hours |
| Nadir Blood Glucose in Each Arm | 48 hours |
| Number of Carbohydrate Interventions for Hypoglycemia | 48 hours |
Countries
United States
Participant flow
Recruitment details
Twelve adult and twelve pediatric subjects with type 1 diabetes and no endogenous insulin secretion participated in two 51-h experiments. The protocol was approved by the Massachusetts General Hospital (MGH) and Boston University Human Research Committees
Participants by arm
| Arm | Count |
|---|---|
| Bi-hormonal Pancreas With Meal-priming Bolus An automatically adapting meal priming bolus was given by the controller at the time each meal was presented | 12 |
| Bi-hormonal Pancreas Without Meal-priming Bolus The insulin controller was entirely reactive to CGMG; there were no meal priming boluses and no meal announcements | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Bi-hormonal Pancreas Without Meal-priming Bolus | Bi-hormonal Pancreas With Meal-priming Bolus | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Continuous | 30.5 years STANDARD_DEVIATION 19 | 30 years STANDARD_DEVIATION 17.7 | 30 years STANDARD_DEVIATION 18 |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 1 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl)
Time frame: 48 hours
Population: Overall number of participants was 24, 12 in each arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bionic Pancreas With Automated Meal-priming Bolus | Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl) | Adults | 132 mg/dl | Standard Deviation 3 |
| Bionic Pancreas With Automated Meal-priming Bolus | Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl) | Adolescents | 162 mg/dl | Standard Deviation 6 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl) | Adults | 146 mg/dl | Standard Deviation 9 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl) | Adolescents | 175 mg/dl | Standard Deviation 9 |
Secondary
Insulin Total Daily Dose
Time frame: 48 hours
Population: Overall number of participants=24 (12 in each arm)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bionic Pancreas With Automated Meal-priming Bolus | Insulin Total Daily Dose | Adults | 0.6 u/kg/day | Standard Deviation 0.2 |
| Bionic Pancreas With Automated Meal-priming Bolus | Insulin Total Daily Dose | Adolescents | 1.1 u/kg/day | Standard Deviation 0.2 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Insulin Total Daily Dose | Adults | 0.7 u/kg/day | Standard Deviation 0.2 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Insulin Total Daily Dose | Adolescents | 1.2 u/kg/day | Standard Deviation 0.2 |
Secondary
Nadir Blood Glucose in Each Arm
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bionic Pancreas With Automated Meal-priming Bolus | Nadir Blood Glucose in Each Arm | 65.9 mg/dl | Standard Deviation 17.4 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Nadir Blood Glucose in Each Arm | 66.4 mg/dl | Standard Deviation 17.8 |
Secondary
Number of Blood Glucose Events < 70 mg/dl
Time frame: 48 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bionic Pancreas With Automated Meal-priming Bolus | Number of Blood Glucose Events < 70 mg/dl | 59 Number of events |
| Bionic Pancreas Without Automated Meal-priming Bolus | Number of Blood Glucose Events < 70 mg/dl | 48 Number of events |
Secondary
Number of Carbohydrate Interventions for Hypoglycemia
Time frame: 48 hours
Population: Overall number of participants=24 (12 in each arm)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bionic Pancreas With Automated Meal-priming Bolus | Number of Carbohydrate Interventions for Hypoglycemia | 12 Carbohydrate Interventions |
| Bionic Pancreas Without Automated Meal-priming Bolus | Number of Carbohydrate Interventions for Hypoglycemia | 10 Carbohydrate Interventions |
Secondary
Percentage of Time Spent With Blood Glucose < 60 mg/dl
Time frame: 48 hours
Population: Overall number of participants=24 (12 in each arm)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bionic Pancreas With Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose < 60 mg/dl | Adults | 2.3 percentage of total time | Standard Deviation 3.9 |
| Bionic Pancreas With Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose < 60 mg/dl | Adolescents | 0.1 percentage of total time | Standard Deviation 0.2 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose < 60 mg/dl | Adults | 1.4 percentage of total time | Standard Deviation 2.7 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose < 60 mg/dl | Adolescents | 0.1 percentage of total time | Standard Deviation 0.2 |
Secondary
Percentage of Time Spent With Blood Glucose 70-180 mg/dl
Time frame: 48 hours
Population: Overall number of participants=24 (12 in each arm)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bionic Pancreas With Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose 70-180 mg/dl | Adults | 80 percentage of total time | Standard Deviation 6 |
| Bionic Pancreas With Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose 70-180 mg/dl | Adolescents | 68 percentage of total time | Standard Deviation 8 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose 70-180 mg/dl | Adolescents | 60 percentage of total time | Standard Deviation 4 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose 70-180 mg/dl | Adults | 70 percentage of total time | Standard Deviation 9 |
Secondary
Percentage of Time Spent With Blood Glucose <70 mg/dl
Time frame: 48 hours
Population: Overall number of participants=24 (12 in each arm)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bionic Pancreas With Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose <70 mg/dl | Adults | 5.1 percentage of total time | Standard Deviation 6.7 |
| Bionic Pancreas With Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose <70 mg/dl | Adolescents | 0.3 percentage of total time | Standard Deviation 0.5 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose <70 mg/dl | Adults | 3.6 percentage of total time | Standard Deviation 4.5 |
| Bionic Pancreas Without Automated Meal-priming Bolus | Percentage of Time Spent With Blood Glucose <70 mg/dl | Adolescents | 0.4 percentage of total time | Standard Deviation 0.7 |