Clinical trial NCT01161862: Integration of Continuous Glucose Monitoring Into a BiHormonal Closed-Loop Artificial Pancreas
Official title: Integration of Continuous Glucose Monitoring Into a Bi-Hormonal Closed-Loop Artificial Pancreas for Automated Management of Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus
Keywords: Closed-loop
Artificial pancreas
Bi-hormonal
Insulin
Glucagon
Diabetes mellitus type 1
Lead sponsor: Boston University Charles River Campus
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Juvenile Diabetes Research Foundation
name: The Leona M. and Harry B. Helmsley Charitable Trust
First posted: 2010-07-14
Enrollment: 24
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl)
timeFrame: 48 hours
Secondary outcomes:
measure: Percentage of Time Spent With Blood Glucose < 60 mg/dl
timeFrame: 48 hours
measure: Percentage of Time Spent With Blood Glucose <70 mg/dl
timeFrame: 48 hours
measure: Percentage of Time Spent With Blood Glucose 70-180 mg/dl
timeFrame: 48 hours
measure: Insulin Total Daily Dose
timeFrame: 48 hours
measure: Number of Carbohydrate Interventions for Hypoglycemia
timeFrame: 48 hours
measure: Number of Blood Glucose Events < 70 mg/dl
timeFrame: 48 hours
measure: Nadir Blood Glucose in Each Arm
timeFrame: 48 hours
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Steven J Russell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Damiano ER, El-Khatib FH, Zheng H, Nathan DM, Russell SJ. A comparative effectiveness analysis of three continuous glucose monitors. Diabetes Care. 2013 Feb;36(2):251-9. doi: 10.2337/dc12-0070. Epub 2012 Dec 28.
citation: Russell SJ, El-Khatib FH, Nathan DM, Magyar KL, Jiang J, Damiano ER. Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas. Diabetes Care. 2012 Nov;35(11):2148-55. doi: 10.2337/dc12-0071. Epub 2012 Aug 24.