Clinical trial NCT01271023: Inpatient Evaluation of an Automated Closed-Loop Control-to-Range System
Official title: Inpatient Evaluation of an Automated Closed-Loop Control-to-Range System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
First posted: 2011-01-06
Enrollment: 57
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test an insulin management system ("Control-to-Range (CTR) system") in an inpatient setting to see if the system is safe and effective enough to test in a future at-home study. The system includes (1) a DexCom Seven Plus Continuous Glucose Monitoring (CGM) device that measures the blood sugar, (2) a laptop computer that determines how much insulin is needed, and (3) an Insulet OmniPod insulin pump that delivers the insulin.

The study will include two hospital stays consisting of meals and exercise scenarios. Both hospital stays will be for 24+ hours during the day and night. The study will include about 50 individuals at 7 clinical centers in the United States, France, Israel, and Italy.

Detailed description: Clinical Research Center (CRC) Session Detail (closed-loop control active for all elements)

Day 1 (24+ hours):

1. Admission at 7:00 AM
2. Standardized breakfast with normal bolus at 9:00 AM
3. Lunch with normal bolus at 1:00 PM
4. Dinner with normal bolus at 7:00 PM
5. Overnight sleep
6. Breakfast with missed meal bolus followed by user alert and correction bolus
7. Discharge

Day 2 (24+ hours):

1. Admission at 7:00 AM
2. Standardized breakfast with normal bolus at 9:00 AM
3. Lunch with normal bolus at 1:00 PM
4. Exercise
5. Dinner with normal bolus at 7:00 PM
6. Overnight sleep
7. Breakfast with overbolus at 7:00 AM
8. Discharge

Meal boluses will be semi-automated, with manual meal announcement by the physician/nurse, automated bolus recommendation by the system, and automated delivery of the bolus following confirmation of the recommendation. Between-meal insulin dosing will be fully automated; bolus confirmation by the physician/nurse will be requested by the closed-loop controller only when it determines that carbohydrates may be necessary to avoid hypoglycemia following the bolus.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of type 1 diabetes for at least one year and using an insulin pump for at least 6 months The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
* Age 12 to 65 years
* Hemoglobin A1c (HbA1c) between 5.0% and 10.5%, as measured with DCA2000 or equivalent device
* For females, not currently known to be pregnant
* Demonstration of proper mental status and cognition for the study
* An understanding of and willingness to follow the protocol and sign the informed consent or assent

Exclusion Criteria:

* Diabetic ketoacidosis in the past 6 months
* Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment
* History of a seizure disorder (except hypoglycemic seizure). Subjects with a history of seizures may be included in the study if they receive written clearance from their neurologist treatment for a seizure disorder
* Coronary artery disease or heart failure. Subjects with a history of coronary artery disease may be included in the study if they receive written clearance from their cardiologist
* Cystic fibrosis
* Active infection
* A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:

  * Inpatient psychiatric treatment in the past 6 months for either the subject or the subject's primary care giver (i.e., parent or guardian)
  * Presence of a known adrenal disorder
  * Abnormal liver or renal function (Transaminase \>2 times the upper limit of normal, Creatinine \> 1.5 mg/dL)
  * Active gastroparesis
  * If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study
  * Uncontrolled thyroid disease
  * Abuse of alcohol Note: Adequately treated thyroid disease and celiac disease do not exclude subjects from enrollment
* A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the exercise protocol
* Current use of a beta blocker medication
* Hematocrit \<30% (labs drawn at screening visit or within one month prior to screening for other purposes will suffice for enrollment purposes related to hematocrit)
* Use of pseudoephedrine 48 hours prior to Clinical Research Center (CRC) admission

Primary outcomes:
measure: Percent of glucose values 71-180 mg/dL of combined day and night readings during the first admission visit
timeFrame: Admission Visit 1
measure: Percent of subjects with blood glucose reading of 71-180 mg/dL 4 hours following the breakfast with a missed meal bolus
timeFrame: 4 hours following the breakfast with a missed meal bolus
measure: Percent of subjects with blood glucose reading of 71-180 mg/dL 5 hours following the breakfast with a meal bolus 30% more than the recommended bolus amount
timeFrame: 5 hours following the breakfast with a meal bolus 30% more than the recommended bolus amount
measure: Percent of subjects with a blood glucose nadir <=60 mg/dL following exercise
timeFrame: Following exercise completion
measure: Overall frequency of hypoglycemia
timeFrame: Includes both admission visits
measure: Overall frequency of hyperglycemia
timeFrame: Includes both admission visits
Secondary outcomes:
measure: Percent of blood glucose values 71-180 mg/dL during the day (9:00AM-11:00PM) of the first admission visit
timeFrame: Admission Visit Day 1 (9:00AM-11:00PM)
measure: Percent of blood glucose values 70-180 mg/dL during the night (11:00PM-8:00AM) of the first admission visit
timeFrame: Admission Visit Night 1 (11:00PM-8:00AM)
measure: Percent of blood glucose values >400 mg/dL during the first admission visit
timeFrame: Admission Visit 1
measure: Percent of blood glucose values <=60 mg/dL during the first admission visit
timeFrame: Admission Visit 1
measure: Percent of subjects with a peak blood glucose >400 mg/dL following the breakfast with a missed meal bolus
timeFrame: 4 hours following the breakfast with a missed meal bolus
measure: Percent of subjects with a nadir blood glucose <=60 mg/dL following the breakfast with a missed meal bolus
timeFrame: 4 hours following the breakfast with a missed meal bolus
measure: Percent of subjects with a peak blood glucose >400 mg/dL following the breakfast with a meal bolus 30% more than the recommended bolus amount
timeFrame: following the breakfast with a meal bolus 30% more than the recommended bolus amount
measure: Percent of subjects with a nadir blood glucose <=60 mg/dL following the breakfast with a meal bolus 30% more than the recommended bolus amount
timeFrame: following the breakfast with a meal bolus 30% more than the recommended bolus amount
Other outcomes:
Locations:
city: Santa Barbara
country: United States
facility: Sansum Diabetes Research Institute
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center- Barbara Davis
state: Colorado
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Montpellier
country: France
facility: Montpellier University Hospital
city: Petah Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Padova
country: Italy
facility: University of Padova
Study officials:
affiliation: Jaeb Center for Health Research
name: Roy W Beck, MD, PhD
role: STUDY_DIRECTOR
affiliation: Sansum Diabetes Research Institute
name: Howard Zisser, MD
role: STUDY_CHAIR
References:
citation: Chase HP, Doyle FJ 3rd, Zisser H, Renard E, Nimri R, Cobelli C, Buckingham BA, Maahs DM, Anderson S, Magni L, Lum J, Calhoun P, Kollman C, Beck RW; Control to Range Study Group. Multicenter closed-loop/hybrid meal bolus insulin delivery with type 1 diabetes. Diabetes Technol Ther. 2014 Oct;16(10):623-32. doi: 10.1089/dia.2014.0050. Epub 2014 Sep 4.
citation: Zisser H, Renard E, Kovatchev B, Cobelli C, Avogaro A, Nimri R, Magni L, Buckingham BA, Chase HP, Doyle FJ 3rd, Lum J, Calhoun P, Kollman C, Dassau E, Farret A, Place J, Breton M, Anderson SM, Dalla Man C, Del Favero S, Bruttomesso D, Filippi A, Scotton R, Phillip M, Atlas E, Muller I, Miller S, Toffanin C, Raimondo DM, De Nicolao G, Beck RW; Control to Range Study Group. Multicenter closed-loop insulin delivery study points to challenges for keeping blood glucose in a safe range by a control algorithm in adults and adolescents with type 1 diabetes from various sites. Diabetes Technol Ther. 2014 Oct;16(10):613-22. doi: 10.1089/dia.2014.0066. Epub 2014 Jul 8.