Back to resultsPilot Study 3 of Outpatient Control-to-Range: Safety and Efficacy With Day-and-Night In-Home Use (CTR3)
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Closed-Loop Control System
Sensor-Augmented Pump (SAP)
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring Artificial Pancreas
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year and an insulin pump for at least 6 months.
- Age >=18 to <70 years.
- HbA1c <10.0%; if HbA1c <6.0% then total daily insulin must be >=0.5 U/kg
- For females, not currently known to be pregnant. If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative urine pregnancy test will be required for all premenopausal women who are not surgically sterile. Subjects who become pregnant will be discontinued from the study.
- Demonstration of proper mental status and cognition for the study.
- Currently using insulin-to-carbohydrate ratio to calculate meal bolus sizes
- Hypoglycemia awareness as demonstrated by a Clarke Hypoglycemia Awareness score of 2 or lower
- Access to internet and cell phone service at home, and a computer for downloading device data.
- Living with significant other or family member committed to participating in all training activities, knowledgeable at all times of the participant's location, and being present and available to provide assistance when system is being used at night.
- Commitment to maintaining uninterrupted availability via cell phone and avoiding any overnight travel for the duration of each two-week period using the closed-loop system.
- An understanding of and willingness to follow the protocol and sign the informed consent.
Exclusion Criteria:
- Admission for diabetic ketoacidosis in the 12 months prior to enrollment.
- Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment.
- History of a seizure disorder (except hypoglycemic seizure), unless written clearance is received from a neurologist.
- Coronary artery disease or heart failure, unless written clearance is received from a cardiologist.
- History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)
- Cystic fibrosis.
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 function test results (Transaminase >2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function
- Abnormal renal function test results (calculated GFR <60); testing required for subjects with diabetes duration of greater than 5 years post onset of puberty
- 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 (TSH undetectable or >10); testing required within three months prior to admission for subjects with a goiter, positive antibodies, or who are on thyroid hormone replacement, and within one year otherwise
- Abuse of alcohol or recreational drugs
- Infectious process not anticipated to resolve prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis)
7. 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 protocol 8. Current use of the following drugs and supplements:
- Acetaminophen
- Any medication being taken to lower blood glucose, such as Pramlintide, Metformin, GLP-1 Analogs such as Liraglutide, and nutraceuticals intended to lower blood glucose
- Beta blockers
- Oral or injectable glucocorticoids
- Any other medication that the investigator believes is a contraindication to the subject's participation
Sites / Locations
- Sansum Diabetes Research Institute
- Stanford University
- University of Virginia
- Montpellier University Hospital
- National Center for Childhood Diabetes- Schneider Children's Medical Center
- University of Padova
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Closed-Loop Control System
Sensor-Augmented Pump (SAP)
Arm Description
Use of an investigational control-to-range automated insulin management (artificial pancreas) system using continuous glucose monitoring (CGM) and subcutaneous insulin pump infusion in individuals with type 1 diabetes in the home environment.
Use of a study-assigned commercial continuous glucose monitoring (CGM) system and commercial insulin pump
Outcomes
Primary Outcome Measures
Time Spent <70 mg/dL - Main Phase, Night Only
Percentage of CGM Measured Glucose Values <70 mg/dl during study Main Phase, night only (23:00 to 07:00)
Secondary Outcome Measures
Time Spent <70 mg/dL - Main Phase, Day and Night
Percentage of CGM Measured Glucose Values <70 mg/dl during study Main Phase
Time Spent <70 mg/dL - Main Phase, Day Only
Percentage of CGM Measured Glucose Values <70 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time in Range 70-180 mg/dL - Main Phase, Day and Night
Percentage of CGM Measured Glucose Values in range 70-180 mg/dl during study Main Phase
Time in Range 70-180 mg/dL - Main Phase, Night Only
Percentage of CGM Measured Glucose Values in range 70-180 mg/dl during study Main Phase, night only (23:00 - 07:00)
Time in Range 70-180 mg/dL - Main Phase, Day Only
Percentage of CGM Measured Glucose Values in range 70-180 mg/dl during study Main Phase, day only (07:00 - 23:00)
Mean Sensor Glucose - Main Phase, Day and Night
Mean CGM sensor glucose during study Main Phase
Mean Sensor Glucose - Main Phase, Night Only
Mean CGM sensor glucose during study Main Phase, night only (23:00 - 07:00)
Mean Sensor Glucose - Main Phase, Day Only
Mean CGM sensor glucose during study Main Phase, day only (07:00 - 23:00)
Glucose Coefficient of Variation - Main Phase, Day and Night
CGM Glucose Coefficient of Variation (CV) during study Main Phase
Glucose Coefficient of Variation - Main Phase, Night Only
CGM Glucose Coefficient of Variation (CV) during study Main Phase, night only (23:00 - 07:00)
Glucose Coefficient of Variation - Main Phase, Day Only
CGM Glucose Coefficient of Variation (CV) during study Main Phase, day only (07:00 - 23:00)
Glucose Standard Deviation - Main Phase, Day and Night
CGM Glucose Standard Deviation (SD) during study Main Phase
Glucose Standard Deviation - Main Phase, Night Only
CGM Glucose Standard Deviation (SD) during study Main Phase, night only (23:00 - 07:00)
Glucose Standard Deviation - Main Phase, Day Only
CGM Glucose Standard Deviation (SD) during study Main Phase, day only (07:00 - 23:00)
Time Spent >180 mg/dL - Main Phase, Day and Night
Percentage of CGM Measured Glucose Values >180 mg/dl during study Main Phase
Time Spent >180 mg/dL - Main Phase, Night Only
Percentage of CGM Measured Glucose Values >180 mg/dl during study Main Phase, night only (23:00 to 07:00)
Time Spent >180 mg/dL - Main Phase, Day Only
Percentage of CGM Measured Glucose Values >180 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Spent <50 mg/dL - Main Phase, Day and Night
Percentage of CGM Measured Glucose Values <50 mg/dl during study Main Phase
Time Spent <50 mg/dL - Main Phase, Night Only
Percentage of CGM Measured Glucose Values <50 mg/dl during study Main Phase, night only (23:00 to 07:00)
Time Spent <50 mg/dL - Main Phase, Day Only
Percentage of CGM Measured Glucose Values <50 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Spent <60 mg/dL - Main Phase, Day and Night
Percentage of CGM Measured Glucose Values <60 mg/dl during study Main Phase
Time Spent <60 mg/dL - Main Phase, Night Only
Percentage of CGM Measured Glucose Values <60 mg/dl during study Main Phase, night only (23:00 - 07:00)
Time Spent <60 mg/dL - Main Phase, Day Only
Percentage of CGM Measured Glucose Values <60 mg/dl during study Main Phase, day only (07:00 - 23:00)
LBGI - Main Phase, Day and Night
Low Blood Glucose Index (LBGI) - Main Phase, Day and Night. The LGBI metric is used to quantify the risk of hypoglycemia. A higher LBGI implies more mild hypoglycemic events or less severe hypoglycemic events.
LBGI - Main Phase, Night Only
Low Blood Glucose Index (LBGI) - Main Phase, night only (23:00 - 07:00). The LGBI metric is used to quantify the risk of hypoglycemia. A higher LBGI implies more mild hypoglycemic events or less severe hypoglycemic events.
LBGI - Main Phase, Day Only
Low Blood Glucose Index (LBGI) - Main Phase, day only (07:00 - 23:00). The LGBI metric is used to quantify the risk of hypoglycemia. A higher LBGI implies more mild hypoglycemic events or less severe hypoglycemic events.
AOC 70 mg/dL - Main Phase, Day and Night
Area Over the Curve (AOC) 70 mg/dL - Main Phase, Day and Night. The hypoglycemia AOC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, a hypoglycemia AOC of 1 mg/dl can denote a glucose of 60 mg/dl for 10% of the time (10 mg/dl below threshold * 10% = 1 mg/dl) or 65 mg/dl for 20% of the time (5 mg/dl below threshold * 20% = 1 mg/dl). Note that it is based on relative (%) rather than absolute time so there is no time element in the resulting units.
AOC 70 mg/dL - Main Phase, Night Only
Area Over the Curve (AOC) 70 mg/dL - Main Phase, night only (23:00 - 07:00). The hypoglycemia AOC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, a hypoglycemia AOC of 1 mg/dl can denote a glucose of 60 mg/dl for 10% of the time (10 mg/dl below threshold * 10% = 1 mg/dl) or 65 mg/dl for 20% of the time (5 mg/dl below threshold * 20% = 1 mg/dl). Note that it is based on relative (%) rather than absolute time so there is no time element in the resulting units.
AOC 70 mg/dL - Main Phase, Day Only
Area Over the Curve (AOC) 70 mg/dL - Main Phase, day only (07:00 - 23:00). The hypoglycemia AOC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, a hypoglycemia AOC of 1 mg/dl can denote a glucose of 60 mg/dl for 10% of the time (10 mg/dl below threshold * 10% = 1 mg/dl) or 65 mg/dl for 20% of the time (5 mg/dl below threshold * 20% = 1 mg/dl). Note that it is based on relative (%) rather than absolute time so there is no time element in the resulting units.
HBGI - Main Phase, Day and Night
High Blood Glucose Index (HBGI) - Main Phase, Day and Night. The HBGI metric is used to quantify the risk of hyperglycemia. A higher HBGI implies more mild hyperglycemic events or less severe hyperglycemic events.
HBGI - Main Phase, Night Only
High Blood Glucose Index (HBGI) - Main Phase, night only (23:00 - 07:00). The HBGI metric is used to quantify the risk of hyperglycemia. A higher HBGI implies more mild hyperglycemic events or less severe hyperglycemic events.
HBGI - Main Phase, Day Only
High Blood Glucose Index (HBGI) - Main Phase, day only (07:00 - 23:00). The HBGI metric is used to quantify the risk of hyperglycemia. A higher HBGI implies more mild hyperglycemic events or less severe hyperglycemic events.
ADRR - Main Phase, Day and Night
Average Daily Risk Range (ADRR) - Main Phase, Day and Night. ADRR is a metric that categorizes risk for hyper and hypoglycemic events. Low risk is scored 0-19, moderate risk is scored 20-40, and high risk is 40 and above.
AUC 180 mg/dL - Main Phase, Day and Night
Area Under the Curve (AUC) 180 mg/dL - Main Phase, Day and Night. The hyperglycemic AUC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, the hyperglycemic AUC is 28 (mg/dl)*days for Patient A and 56 (mg/dl)*days for Patient B when using 180 as the threshold. But this is artificial because Patient B wore the sensor twice as long. So we similarly scale it relative to the number of readings to reflect a mean rather than a sum. So we say hyperglycemic AUC = 4 mg/dl for both patients. Note that time disappears from the units in the scaled version. It represents the mean value of max(glucose-180, 0).
AUC 180 mg/dL - Main Phase, Night Only
Area Under the Curve (AUC) 180 mg/dL - Main Phase, night only (23:00 - 07:00). The hyperglycemic AUC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, the hyperglycemic AUC is 28 (mg/dl)*days for Patient A and 56 (mg/dl)*days for Patient B when using 180 as the threshold. But this is artificial because Patient B wore the sensor twice as long. So we similarly scale it relative to the number of readings to reflect a mean rather than a sum. So we say hyperglycemic AUC = 4 mg/dl for both patients. Note that time disappears from the units in the scaled version. It represents the mean value of max(glucose-180, 0).
AUC 180 mg/dL - Main Phase, Day Only
Area Under the Curve (AUC) 180 mg/dL - Main Phase, day only (07:00 - 23:00). The hyperglycemic AUC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, the hyperglycemic AUC is 28 (mg/dl)*days for Patient A and 56 (mg/dl)*days for Patient B when using 180 as the threshold. But this is artificial because Patient B wore the sensor twice as long. So we similarly scale it relative to the number of readings to reflect a mean rather than a sum. So we say hyperglycemic AUC = 4 mg/dl for both patients. Note that time disappears from the units in the scaled version. It represents the mean value of max(glucose-180, 0).
Time Spent >250 mg/dL - Main Phase, Day and Night
Percentage of CGM Measured Glucose Values >250 mg/dl during study Main Phase
Time Spent >250 mg/dL - Main Phase, Night Only
Percentage of CGM Measured Glucose Values >250 mg/dl during study Main Phase, night only (23:00 to 07:00)
Time Spent >250 mg/dL - Main Phase, Day Only
Percentage of CGM Measured Glucose Values >250 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Spent >300 mg/dL - Main Phase, Day and Night
Percentage of CGM Measured Glucose Values >300 mg/dl during study Main Phase
Time Spent >300 mg/dL - Main Phase, Night Only
Percentage of CGM Measured Glucose Values >300 mg/dl during study Main Phase, night only (23:00 to 07:00)
Time Spent >300 mg/dL - Main Phase, Day Only
Percentage of CGM Measured Glucose Values >300 mg/dl during study Main Phase, day only (07:00 - 23:00)
Full Information
NCT ID
NCT02137512
First Posted
May 12, 2014
Last Updated
October 26, 2018
Sponsor
Jaeb Center for Health Research
1. Study Identification
Unique Protocol Identification Number
NCT02137512
Brief Title
Pilot Study 3 of Outpatient Control-to-Range: Safety and Efficacy With Day-and-Night In-Home Use
Acronym
CTR3
Official Title
Pilot Study 3 of Outpatient Control-to-Range: Safety and Efficacy With Day-and-Night In-Home Use
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jaeb Center for Health Research
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to see if an automated insulin management system ("study system") can safely be used at home to manage blood sugar. The study system includes (1) a CGM that measures glucose levels, (2) a computer program on a smartphone that determines how much insulin is needed and allows the study participant user to control the whole system, and (3) an insulin pump that delivers the insulin. The CGM will be from Dexcom. The pump will be from Roche. The CGM and pump are similar to the devices that are currently available for people to purchase and use. However, the smartphone device, the CGM sensor type used with it, and the overall study system can only be used for research at this time.
The study will be completed by about 24 individuals at 6 centers in the United States and Europe. This study has several phases and will take about 11-14 weeks to complete depending on whether the study participant is a CGM user or not.
At selected sites (based on subject eligibility and availability), approximately 10-20 subjects who exhibit safe and competent use of the system at home will be given the option to continue home use of the system in Day-and-Night Closed-Loop mode for up to 5 months.
Detailed Description
The study phases are as follows:
Screening visit to see if you are eligible for the study and to determine how long you will need to use the study CGM (visit 1)
Up to 3 weeks using the study CGM (depends on your current CGM use), followed by an office visit (visit 2)
2 weeks using the study insulin pump and study CGM together
Full day visit in clinic or hotel for training using the system (visit 3)
1 week using the system without automated insulin delivery or suspension
2-day hotel or clinic visit for closed-loop training (visit 4),
16-19 days using the system in the evening and overnight only followed by an office visit (visit 5)
16-19 days using the system for the full 24 hours
Final study clinic visit (visit 6)
Option 5 month extension phase of day-and-night closed-loop home use
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Artificial Pancreas
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Closed-Loop Control System
Arm Type
Experimental
Arm Description
Use of an investigational control-to-range automated insulin management (artificial pancreas) system using continuous glucose monitoring (CGM) and subcutaneous insulin pump infusion in individuals with type 1 diabetes in the home environment.
Arm Title
Sensor-Augmented Pump (SAP)
Arm Type
Active Comparator
Arm Description
Use of a study-assigned commercial continuous glucose monitoring (CGM) system and commercial insulin pump
Intervention Type
Device
Intervention Name(s)
Closed-Loop Control System
Other Intervention Name(s)
Diabetes Assistant (DiAs)
Intervention Description
This investigational device system included the following components:
DiAs - a smart-phone medical platform;
Dexcom G4 Platinum CGM system connected to DiAs via CGM receiver and USB-Bluetooth relay hardware;
Roche Accu-Chek insulin pump connected to DiAs via wireless Bluetooth;
Remote Monitoring Server connected to DiAs via 3G or local Wi-Fi network
Modular Closed-Loop Control Algorithm Running on DiAs, which is of Control-to-Range (CTR) class
Intervention Type
Device
Intervention Name(s)
Sensor-Augmented Pump (SAP)
Intervention Description
This commercial device system included the following components:
Dexcom G4 Platinum CGM system;
Roche Accu-Chek insulin pump
Primary Outcome Measure Information:
Title
Time Spent <70 mg/dL - Main Phase, Night Only
Description
Percentage of CGM Measured Glucose Values <70 mg/dl during study Main Phase, night only (23:00 to 07:00)
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Time Spent <70 mg/dL - Main Phase, Day and Night
Description
Percentage of CGM Measured Glucose Values <70 mg/dl during study Main Phase
Time Frame
2 weeks
Title
Time Spent <70 mg/dL - Main Phase, Day Only
Description
Percentage of CGM Measured Glucose Values <70 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Title
Time in Range 70-180 mg/dL - Main Phase, Day and Night
Description
Percentage of CGM Measured Glucose Values in range 70-180 mg/dl during study Main Phase
Time Frame
2 weeks
Title
Time in Range 70-180 mg/dL - Main Phase, Night Only
Description
Percentage of CGM Measured Glucose Values in range 70-180 mg/dl during study Main Phase, night only (23:00 - 07:00)
Time Frame
2 weeks
Title
Time in Range 70-180 mg/dL - Main Phase, Day Only
Description
Percentage of CGM Measured Glucose Values in range 70-180 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Title
Mean Sensor Glucose - Main Phase, Day and Night
Description
Mean CGM sensor glucose during study Main Phase
Time Frame
2 weeks
Title
Mean Sensor Glucose - Main Phase, Night Only
Description
Mean CGM sensor glucose during study Main Phase, night only (23:00 - 07:00)
Time Frame
2 weeks
Title
Mean Sensor Glucose - Main Phase, Day Only
Description
Mean CGM sensor glucose during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Title
Glucose Coefficient of Variation - Main Phase, Day and Night
Description
CGM Glucose Coefficient of Variation (CV) during study Main Phase
Time Frame
2 weeks
Title
Glucose Coefficient of Variation - Main Phase, Night Only
Description
CGM Glucose Coefficient of Variation (CV) during study Main Phase, night only (23:00 - 07:00)
Time Frame
2 weeks
Title
Glucose Coefficient of Variation - Main Phase, Day Only
Description
CGM Glucose Coefficient of Variation (CV) during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Title
Glucose Standard Deviation - Main Phase, Day and Night
Description
CGM Glucose Standard Deviation (SD) during study Main Phase
Time Frame
2 weeks
Title
Glucose Standard Deviation - Main Phase, Night Only
Description
CGM Glucose Standard Deviation (SD) during study Main Phase, night only (23:00 - 07:00)
Time Frame
2 weeks
Title
Glucose Standard Deviation - Main Phase, Day Only
Description
CGM Glucose Standard Deviation (SD) during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Title
Time Spent >180 mg/dL - Main Phase, Day and Night
Description
Percentage of CGM Measured Glucose Values >180 mg/dl during study Main Phase
Time Frame
2 weeks
Title
Time Spent >180 mg/dL - Main Phase, Night Only
Description
Percentage of CGM Measured Glucose Values >180 mg/dl during study Main Phase, night only (23:00 to 07:00)
Time Frame
2 weeks
Title
Time Spent >180 mg/dL - Main Phase, Day Only
Description
Percentage of CGM Measured Glucose Values >180 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Title
Time Spent <50 mg/dL - Main Phase, Day and Night
Description
Percentage of CGM Measured Glucose Values <50 mg/dl during study Main Phase
Time Frame
2 weeks
Title
Time Spent <50 mg/dL - Main Phase, Night Only
Description
Percentage of CGM Measured Glucose Values <50 mg/dl during study Main Phase, night only (23:00 to 07:00)
Time Frame
2 weeks
Title
Time Spent <50 mg/dL - Main Phase, Day Only
Description
Percentage of CGM Measured Glucose Values <50 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Title
Time Spent <60 mg/dL - Main Phase, Day and Night
Description
Percentage of CGM Measured Glucose Values <60 mg/dl during study Main Phase
Time Frame
2 weeks
Title
Time Spent <60 mg/dL - Main Phase, Night Only
Description
Percentage of CGM Measured Glucose Values <60 mg/dl during study Main Phase, night only (23:00 - 07:00)
Time Frame
2 weeks
Title
Time Spent <60 mg/dL - Main Phase, Day Only
Description
Percentage of CGM Measured Glucose Values <60 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Title
LBGI - Main Phase, Day and Night
Description
Low Blood Glucose Index (LBGI) - Main Phase, Day and Night. The LGBI metric is used to quantify the risk of hypoglycemia. A higher LBGI implies more mild hypoglycemic events or less severe hypoglycemic events.
Time Frame
2 weeks
Title
LBGI - Main Phase, Night Only
Description
Low Blood Glucose Index (LBGI) - Main Phase, night only (23:00 - 07:00). The LGBI metric is used to quantify the risk of hypoglycemia. A higher LBGI implies more mild hypoglycemic events or less severe hypoglycemic events.
Time Frame
2 weeks
Title
LBGI - Main Phase, Day Only
Description
Low Blood Glucose Index (LBGI) - Main Phase, day only (07:00 - 23:00). The LGBI metric is used to quantify the risk of hypoglycemia. A higher LBGI implies more mild hypoglycemic events or less severe hypoglycemic events.
Time Frame
2 weeks
Title
AOC 70 mg/dL - Main Phase, Day and Night
Description
Area Over the Curve (AOC) 70 mg/dL - Main Phase, Day and Night. The hypoglycemia AOC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, a hypoglycemia AOC of 1 mg/dl can denote a glucose of 60 mg/dl for 10% of the time (10 mg/dl below threshold * 10% = 1 mg/dl) or 65 mg/dl for 20% of the time (5 mg/dl below threshold * 20% = 1 mg/dl). Note that it is based on relative (%) rather than absolute time so there is no time element in the resulting units.
Time Frame
2 weeks
Title
AOC 70 mg/dL - Main Phase, Night Only
Description
Area Over the Curve (AOC) 70 mg/dL - Main Phase, night only (23:00 - 07:00). The hypoglycemia AOC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, a hypoglycemia AOC of 1 mg/dl can denote a glucose of 60 mg/dl for 10% of the time (10 mg/dl below threshold * 10% = 1 mg/dl) or 65 mg/dl for 20% of the time (5 mg/dl below threshold * 20% = 1 mg/dl). Note that it is based on relative (%) rather than absolute time so there is no time element in the resulting units.
Time Frame
2 weeks
Title
AOC 70 mg/dL - Main Phase, Day Only
Description
Area Over the Curve (AOC) 70 mg/dL - Main Phase, day only (07:00 - 23:00). The hypoglycemia AOC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, a hypoglycemia AOC of 1 mg/dl can denote a glucose of 60 mg/dl for 10% of the time (10 mg/dl below threshold * 10% = 1 mg/dl) or 65 mg/dl for 20% of the time (5 mg/dl below threshold * 20% = 1 mg/dl). Note that it is based on relative (%) rather than absolute time so there is no time element in the resulting units.
Time Frame
2 weeks
Title
HBGI - Main Phase, Day and Night
Description
High Blood Glucose Index (HBGI) - Main Phase, Day and Night. The HBGI metric is used to quantify the risk of hyperglycemia. A higher HBGI implies more mild hyperglycemic events or less severe hyperglycemic events.
Time Frame
2 weeks
Title
HBGI - Main Phase, Night Only
Description
High Blood Glucose Index (HBGI) - Main Phase, night only (23:00 - 07:00). The HBGI metric is used to quantify the risk of hyperglycemia. A higher HBGI implies more mild hyperglycemic events or less severe hyperglycemic events.
Time Frame
2 weeks
Title
HBGI - Main Phase, Day Only
Description
High Blood Glucose Index (HBGI) - Main Phase, day only (07:00 - 23:00). The HBGI metric is used to quantify the risk of hyperglycemia. A higher HBGI implies more mild hyperglycemic events or less severe hyperglycemic events.
Time Frame
2 weeks
Title
ADRR - Main Phase, Day and Night
Description
Average Daily Risk Range (ADRR) - Main Phase, Day and Night. ADRR is a metric that categorizes risk for hyper and hypoglycemic events. Low risk is scored 0-19, moderate risk is scored 20-40, and high risk is 40 and above.
Time Frame
2 weeks
Title
AUC 180 mg/dL - Main Phase, Day and Night
Description
Area Under the Curve (AUC) 180 mg/dL - Main Phase, Day and Night. The hyperglycemic AUC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, the hyperglycemic AUC is 28 (mg/dl)*days for Patient A and 56 (mg/dl)*days for Patient B when using 180 as the threshold. But this is artificial because Patient B wore the sensor twice as long. So we similarly scale it relative to the number of readings to reflect a mean rather than a sum. So we say hyperglycemic AUC = 4 mg/dl for both patients. Note that time disappears from the units in the scaled version. It represents the mean value of max(glucose-180, 0).
Time Frame
2 weeks
Title
AUC 180 mg/dL - Main Phase, Night Only
Description
Area Under the Curve (AUC) 180 mg/dL - Main Phase, night only (23:00 - 07:00). The hyperglycemic AUC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, the hyperglycemic AUC is 28 (mg/dl)*days for Patient A and 56 (mg/dl)*days for Patient B when using 180 as the threshold. But this is artificial because Patient B wore the sensor twice as long. So we similarly scale it relative to the number of readings to reflect a mean rather than a sum. So we say hyperglycemic AUC = 4 mg/dl for both patients. Note that time disappears from the units in the scaled version. It represents the mean value of max(glucose-180, 0).
Time Frame
2 weeks
Title
AUC 180 mg/dL - Main Phase, Day Only
Description
Area Under the Curve (AUC) 180 mg/dL - Main Phase, day only (07:00 - 23:00). The hyperglycemic AUC is scaled to the number of CGM readings so the time factor cancels out. Technically, the units would be mg/dl, but this might seem unintuitive since it is incremental relative to a threshold. For example, the hyperglycemic AUC is 28 (mg/dl)*days for Patient A and 56 (mg/dl)*days for Patient B when using 180 as the threshold. But this is artificial because Patient B wore the sensor twice as long. So we similarly scale it relative to the number of readings to reflect a mean rather than a sum. So we say hyperglycemic AUC = 4 mg/dl for both patients. Note that time disappears from the units in the scaled version. It represents the mean value of max(glucose-180, 0).
Time Frame
2 weeks
Title
Time Spent >250 mg/dL - Main Phase, Day and Night
Description
Percentage of CGM Measured Glucose Values >250 mg/dl during study Main Phase
Time Frame
2 weeks
Title
Time Spent >250 mg/dL - Main Phase, Night Only
Description
Percentage of CGM Measured Glucose Values >250 mg/dl during study Main Phase, night only (23:00 to 07:00)
Time Frame
2 weeks
Title
Time Spent >250 mg/dL - Main Phase, Day Only
Description
Percentage of CGM Measured Glucose Values >250 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Title
Time Spent >300 mg/dL - Main Phase, Day and Night
Description
Percentage of CGM Measured Glucose Values >300 mg/dl during study Main Phase
Time Frame
2 weeks
Title
Time Spent >300 mg/dL - Main Phase, Night Only
Description
Percentage of CGM Measured Glucose Values >300 mg/dl during study Main Phase, night only (23:00 to 07:00)
Time Frame
2 weeks
Title
Time Spent >300 mg/dL - Main Phase, Day Only
Description
Percentage of CGM Measured Glucose Values >300 mg/dl during study Main Phase, day only (07:00 - 23:00)
Time Frame
2 weeks
Other Pre-specified Outcome Measures:
Title
Mean Sensor Glucose - Extension Phase
Description
Mean CGM sensor glucose during Extension Phase
Time Frame
3 months
Title
Change in HbA1c - Extension Phase
Description
Comparison of HbA1c collected at baseline and at the end of the 5-month extension phase
Time Frame
5 months
Title
Time Spent <3.9 mmol/L (70 mg/dL) - Extension Phase
Description
Percentage of CGM Measured Glucose Values <3.9 mmol/L (70 mg/dL) during study Extension Phase
Time Frame
3 months
Title
Time Spent <3.3 mmol/L (60 mg/dL) - Extension Phase
Description
Percentage of CGM Measured Glucose Values <3.3 mmol/L (60 mg/dL) during study Extension Phase
Time Frame
3 months
Title
Time Spent <2.8 mmol/L (50 mg/dL) - Extension Phase
Description
Percentage of CGM Measured Glucose Values <2.8 mmol/L (50 mg/dL) during study Extension Phase
Time Frame
3 months
Title
Time in Range 3.9-10.0 mmol/L (70-180 mg/dL) - Extension Phase
Description
Percentage of CGM Measured Glucose Values in range 3.9-10.0 mmol/L (70-180 mg/dL)
Time Frame
3 months
Title
Time Spent >10.0 mmol/L (180 mg/dL) - Extension Phase
Description
Percentage of CGM Measured Glucose Values >10.0 mmol/L (180 mg/dL) during study Extension Phase
Time Frame
3 months
Title
Time Spent >13.9 mmol/L (250 mg/dL) - Extension Phase
Description
Percentage of CGM Measured Glucose Values >13.9 mmol/L (250 mg/dL) during study Extension Phase
Time Frame
3 months
Title
Time Spent >16.7 mmol/L (300 mg/dL) - Extension Phase
Description
Percentage of CGM Measured Glucose Values >16.7 mmol/L (300 mg/dL) during study Extension Phase
Time Frame
3 months
Title
Episodes of Severe Hypoglycemia Events - Extension Phase
Description
Episodes of severe hypoglycemia events during the 5-month extension phase defined as an event requiring assistance of another person due to altered consciousness to actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the subject was impaired cognitively to the point that he/she was unable to treat him or herself, was unable to verbalize his or her needs, was incoherent, disoriented, and/or combative, or experienced seizure or coma. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. If plasma glucose measurements are not available during such an event, neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Time Frame
5 months
Title
Episodes of Diabetic Ketoacidosis (DKA) Events - Extension Phase
Description
Episodes of DKA events that occurred during the 5-month extension phase
Time Frame
5 months
Title
Reported Serious Adverse Events - Extension Phase
Description
Reported serious adverse events during the 5-month extension phase
Time Frame
5 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year and an insulin pump for at least 6 months.
Age >=18 to <70 years.
HbA1c <10.0%; if HbA1c <6.0% then total daily insulin must be >=0.5 U/kg
For females, not currently known to be pregnant. If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative urine pregnancy test will be required for all premenopausal women who are not surgically sterile. Subjects who become pregnant will be discontinued from the study.
Demonstration of proper mental status and cognition for the study.
Currently using insulin-to-carbohydrate ratio to calculate meal bolus sizes
Hypoglycemia awareness as demonstrated by a Clarke Hypoglycemia Awareness score of 2 or lower
Access to internet and cell phone service at home, and a computer for downloading device data.
Living with significant other or family member committed to participating in all training activities, knowledgeable at all times of the participant's location, and being present and available to provide assistance when system is being used at night.
Commitment to maintaining uninterrupted availability via cell phone and avoiding any overnight travel for the duration of each two-week period using the closed-loop system.
An understanding of and willingness to follow the protocol and sign the informed consent.
Exclusion Criteria:
Admission for diabetic ketoacidosis in the 12 months prior to enrollment.
Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment.
History of a seizure disorder (except hypoglycemic seizure), unless written clearance is received from a neurologist.
Coronary artery disease or heart failure, unless written clearance is received from a cardiologist.
History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)
Cystic fibrosis.
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 function test results (Transaminase >2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function
Abnormal renal function test results (calculated GFR <60); testing required for subjects with diabetes duration of greater than 5 years post onset of puberty
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 (TSH undetectable or >10); testing required within three months prior to admission for subjects with a goiter, positive antibodies, or who are on thyroid hormone replacement, and within one year otherwise
Abuse of alcohol or recreational drugs
Infectious process not anticipated to resolve prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis)
7. 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 protocol 8. Current use of the following drugs and supplements:
Acetaminophen
Any medication being taken to lower blood glucose, such as Pramlintide, Metformin, GLP-1 Analogs such as Liraglutide, and nutraceuticals intended to lower blood glucose
Beta blockers
Oral or injectable glucocorticoids
Any other medication that the investigator believes is a contraindication to the subject's participation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roy Beck, MD, PhD
Organizational Affiliation
Jaeb Center for Health Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Boris Kovatchev, PhD
Organizational Affiliation
University of Virginia
Official's Role
Study Chair
Facility Information:
Facility Name
Sansum Diabetes Research Institute
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Montpellier University Hospital
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
National Center for Childhood Diabetes- Schneider Children's Medical Center
City
Petah Tikva
ZIP/Postal Code
49202
Country
Israel
Facility Name
University of Padova
City
Padova
ZIP/Postal Code
93106
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
27208316
Citation
Anderson SM, Raghinaru D, Pinsker JE, Boscari F, Renard E, Buckingham BA, Nimri R, Doyle FJ 3rd, Brown SA, Keith-Hynes P, Breton MD, Chernavvsky D, Bevier WC, Bradley PK, Bruttomesso D, Del Favero S, Calore R, Cobelli C, Avogaro A, Farret A, Place J, Ly TT, Shanmugham S, Phillip M, Dassau E, Dasanayake IS, Kollman C, Lum JW, Beck RW, Kovatchev B; Control to Range Study Group. Multinational Home Use of Closed-Loop Control Is Safe and Effective. Diabetes Care. 2016 Jul;39(7):1143-50. doi: 10.2337/dc15-2468. Epub 2016 Apr 13.
Results Reference
result
Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/27208316
Description
Multinational Home Use of Closed-Loop Control Is Safe and Effective
Learn more about this trial
Pilot Study 3 of Outpatient Control-to-Range: Safety and Efficacy With Day-and-Night In-Home Use
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