Integration of Continuous Glucose Monitoring Into a BiHormonal Closed-Loop Artificial Pancreas

Not Applicable

Completed

Conditions: Diabetes Mellitus

Interventions: Device: Bi-hormonal (insulin and glucagon) artificial pancreas

Registration Number: NCT01161862

Lead Sponsor: Boston University Charles River Campus

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bi-hormonal without meal-priming bolus	Bi-hormonal (insulin and glucagon) artificial pancreas	The insulin controller was entirely reactive to CGMG; there were no meal priming boluses and no meal announcements
Bi-hormonal with meal-priming bolus	Bi-hormonal (insulin and glucagon) artificial pancreas	The first meal-priming bolus was solely based on weight (0.05 U/kg), after which meal-priming boluses were automatically adapted by the control system online targeting 75% of the anticipated insulin needed in the first four hours after the start of the meal

Primary Outcome Measures

Name	Time	Method
Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl)	48 hours

Secondary Outcome Measures

Name	Time	Method
Nadir Blood Glucose in Each Arm	48 hours
Percentage of Time Spent With Blood Glucose <70 mg/dl	48 hours
Insulin Total Daily Dose	48 hours
Number of Carbohydrate Interventions for Hypoglycemia	48 hours
Number of Blood Glucose Events < 70 mg/dl	48 hours
Percentage of Time Spent With Blood Glucose < 60 mg/dl	48 hours
Percentage of Time Spent With Blood Glucose 70-180 mg/dl	48 hours

Trial Locations

Locations (1): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States