DCLP4: The International Diabetes Closed Loop (iDCL) Trial: Protocol 4
Study Details
Study Description
Brief Summary
The investigators aim to compare the efficacy and safety of an AID system using an adaptive MPC algorithm versus SAP (which may or may not include PLGS; to be referred to as SAP) in people with type 1 diabetes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
A randomized crossover trial will compare the efficacy and safety of an automated insulin delivery (AID) study system using an adaptive Model Predictive Control (MPC) algorithm versus SAP (which may or may not include PLGS; to be referred to as SAP) therapy in people with type 1 diabetes for 13 weeks in each arm of the study. A Pilot Phase using the study system for 10-14 days will be conducted prior to the crossover trial.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Artificial Pancreas Subjects will be provided the Interoperable Artificial Pancreas System (iAPS) which includes the iAPS phone platform, a study insulin pump, study continuous glucose monitor (CGM), and a study glucometer. This iAPS is designed to help control blood sugar in people living with type 1 diabetes. |
Device: interoperable Artificial Pancreas System (iAPS)
Use of the iAPS at home for 13 weeks, with weekly adaptation of insulin delivery settings occurring automatically in the iAPS.
|
| Active Comparator: Sensor Augmented Pump/Predictive Low Glucose Suspend Subjects will continue use of home insulin pump with a study continuous glucose monitor (CGM) and study glucometer. Subject may use home pump in PLGS mode if this is supported and compatible with the study sensor. |
Other: Sensor-Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS)
Use of personal pump with study CGM & glucometer at home for 13 weeks.
|
Outcome Measures
Primary Outcome Measures
- CGM Time in Range 70-180 mg/dL [13 weeks]
Superiority for time in range 70-180 mg/dL and non-inferiority for time <54 mg/dL measured with CGM will be considered primary endpoints, analyzed using a hierarchical gatekeeping testing procedure
- Non-inferiority for CGM time <54 mg/dL [13 weeks]
Superiority for time in range 70-180 mg/dL and non-inferiority for time <54 mg/dL measured with CGM will be considered primary endpoints, analyzed using a hierarchical gatekeeping testing procedure
Secondary Outcome Measures
- CGM Mean Glucose [13 weeks]
CGM-measured mean glucose (mg/dL)
- CGM Time > 180 [13 weeks]
CGM time > 180 mg/dL
- CGM Time > 250 [13 weeks]
CGM time > 250 mg/dL
- CGM Time < 70 [13 weeks]
CGM time < 70 mg/dL
- CGM Time < 54 (Superiority) [13 weeks]
CGM time < 54 mg/dL (Superiority)
- Coefficient of Variation [13 weeks]
CGM measured glucose variability measured with the coefficient of variation (CV)
- CGM Time in Range 70-140 mg/dL [13 weeks]
CGM-measured % in range 70-140 mg/dL
- Standard Deviation [13 weeks]
CGM measured glucose variability measured with the standard deviation (SD)
- CGM Time < 60 [13 weeks]
CGM time < 60 mg/dL
- LBGI [13 weeks]
Low blood glucose index by CGM with higher index indicating higher risk of hypoglycemia. Values <1 suggest minimal risk. Index of risk of low blood glucose excursion based on a standard formula for non-linear transformation of the blood glucose scale (Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke WL: Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index. Diabetes Care 21:1870-1875, 1998)
- CGM Hypoglycemia Events [13 weeks]
CGM-measured events of at least 15 consecutive minutes <70mg/dL per week
- CGM Time > 300 [13 weeks]
CGM time > 300 mg/dL
- HBGI [13 weeks]
High blood glucose index by CGM with higher values indicating higher risk of hyperglycemia. Index of risk of high blood glucose excursion based on a standard formula for non-linear transformation of the blood glucose scale (Kovatchev BP, Cox DJ, Kumar A, Gonder-Frederick L, Clarke WL. Algorithmic evaluation of metabolic control and risk of severe hypoglycemia in type 1 and type 2 diabetes using self-monitoring blood glucose data. Diabetes Technol Ther 2003;5:817-828pmid:14633347)
- HbA1c at 13 weeks [13 weeks]
Hemiglobin A1c measured after completing each study arm
- Number of Participants With HbA1c <7.0% at 13 weeks [13 weeks]
Number of participants HbA1c <7.0% after completing each study arm
- Number of Participants With HbA1c <7.5% at 13 weeks [3 months]
Number of participants HbA1c <7.5% after completing each study arm
- HbA1c improvement from baseline to 13 weeks >0.5% [13 weeks]
HbA1c improvement from baseline to 13 weeks >0.5% after completing each study arm
- HbA1c improvement from baseline to 13 weeks >1% [13 weeks]
HbA1c improvement from baseline to 13 weeks >1% after completing each study arm
- HbA1c relative improvement from baseline to 13 weeks >10% [13 weeks]
HbA1c relative improvement from baseline to 3 months >10% after completion of each study arm
- Number of Participants With HbA1c Improvement From Baseline to 3 months >1.0% or HbA1c <7.0% after 3 months [13 weeks]
HbA1c improvement from baseline to 13 weeks >1.0% or HbA1c <7.0% after 13 weeks in each arm
- Diabetes Distress Scale at 13 weeks - total score and 4 subscales: Emotional burden, Physician-related distress, Regimen-related distress, Interpersonal distress [13 weeks]
Diabetes Distress Scale for adults has 28 items rated on a 6 point Likert scale that ranges from 1 (not a problem) to 6 (a very serious problem). The total score is the mean of the sum of responses and ranges from 1 to 6 where a higher score indicates greater degrees of diabetes distress.
- Glucose Monitoring Satisfaction Survey [13 weeks]
Satisfaction, burden, and total scores
- Hypoglycemia Confidence Scale [13 weeks]
Hypoglycemia Confidence Scale has 20 items which are rated on a 4-point Likert Scale ranging from 1 (not confident at all) to 4 (very confident) with higher scores indicating higher confidence in dealing with hypoglycemia. A single score is computed by calculating the mean of the sum of all items and ranges from 1 to 4.
- Diabetes Technology Attitudes Survey [13 weeks]
Diabetes Technology Attitudes Survey
- INSPIRE survey scores - following study system period only [13 weeks]
The INSPIRE questionnaire assesses user expectations and experiences with Insulin Delivery Systems: Perceptions, Ideas, Reflections, Expectations (INSPIRE). Survey total scores are computed by calculating the mean of the sum of all item ratings then multiplying the mean by 25 to scale the score to a range from 0 to 100. Higher scores indicate a more positive perception of insulin delivery systems. Items are rated on a 5 point Likert scale ranging from 0 (strongly disagree) to 4 (strongly agree). The Adult survey has 22 items, the Teens/Adolescents survey has 17 items and the Parent survey has 21 items.
- SUS survey scores - following study system period [13 weeks]
System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicate better perceived usability
- Total Daily Insulin [13 weeks]
Total Daily Insulin (units)
- Basal: bolus insulin ratio [13 weeks]
Basal: bolus insulin ratio
- Weight [13 weeks]
Weight (kg)
- BMI [13 weeks]
Body Mass Index (BMI) kg/m^2
Other Outcome Measures
- CGM metrics by time of day [13 weeks]
Calculate all CGM metrics listed above (including the primary outcome) for: All 24 hours of the day, Daytime only (06:00AM to 00:00AM), Nighttime only (00:00AM to 06:00AM).
- Number of Participants With Severe Hypoglycemia (Per Protocol) [13 weeks]
Severe hypoglycemia (per protocol)
- Number of Participants With Diabetic Ketoacidosis (Per Protocol) [13 weeks]
Diabetic ketoacidosis (per protocol)
- Ketone Events Defined as Day With Ketone Level >1.0 mmol/L [13 weeks]
Ketone events defined as day with ketone level >1.0 mmol/L
- CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL) [3 months]
CGM-measured hypoglycemic events (>15 minutes with glucose concentration <54 mg/dL) in each arm.
- CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL) [3 months]
CGM-measured hyperglycemic events (>15 minutes with glucose concentration >300 mg/dL) in each arm.
- BG-measured Hypoglycemic Events (One BG Record <54 mg/dL [13 weeks]
BG-measured Hypoglycemic Events (One BG Record <54 mg/dL
- Worsening of HbA1c From Baseline to 26 Weeks by >0.5% [13 weeks]
Worsening of HbA1c from baseline to 26 weeks by >0.5%
- Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) [13 weeks]
Other serious adverse events (SAE) and serious adverse device events (SADE)
- Adverse Device Effects (ADE) [13 weeks]
Adverse device effects (ADE)
- Unanticipated Adverse Device Effects (UADE) [13 weeks]
Unanticipated adverse device effects (UADE)
- Number of Participants With SH Events [13 weeks]
For this outcome, mean +/- SD or summary statistics appropriate to the distribution will be tabulated by treatment group
- SH Event Rate Per 100 Person-years [13 weeks]
For this outcome, severe hypoglycemia event rate per 100 person-years will be calculated as a rate.
- Number of Participants With DKA Events [13 weeks]
For this outcome, number of participants with diabetic ketoacidosis (DKA) will be tabulated.
- DKA Event Rate Per 100 Person-years [13 weeks]
For this outcome, the diabetic ketoacidosis event rate per 100 person-years will be calculated as a rate.
- Any Adverse Event Rate Per 100 Person-years [13 weeks]
For this outcome, the adverse event rate per 100 person-years calculated as a rate.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year
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Using an insulin pump for at least 3 months (which may include use of automated features)
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Familiarity and use of a carbohydrate ratio for meal boluses
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Age ≥18.0 years old
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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 serum or urine pregnancy test will be required for all females of child-bearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued.
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If using a personal CGM, willingness to use a Dexcom G6 CGM and discontinue personal CGM use during the study
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Willing not to begin use of, or not to continue use of if currently using, a personal AID (closed loop control) system during the study; note if the system offers an open-loop mode or can be switched to a PLGS mode that is compatible with the Dexcom G6, the system may be used during the study in these modes only
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Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study
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Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial, and not to use Afrezza during the trial
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Investigator believes that the participant can successfully and safely operate all study devices and is capable of adhering to the protocol
Exclusion Criteria:
-
Use of Afrezza or any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas) unless participant is willing to discontinue during the trial.
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Two or more episodes of DKA requiring an emergency room visit or hospitalization in the past 6 months
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Two or more episodes of severe hypoglycemia with seizure or loss of consciousness in the last 6 months
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Hemophilia or any other bleeding disorder
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A medical or other condition that in the opinion of the investigator could create a safety concern for the participant or put the study at risk. History of frequent severe hypoglycemia or history of frequent severe hyperglycemia and/or ketosis, without emergency room visit or hospitalization, due to poor diabetes self-management may be disqualifying per investigator judgment
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Participation in another pharmaceutical or device trial at the time of enrollment or during the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sansum Diabetes Research Institute | Santa Barbara | California | United States | 93105 |
| 2 | Stanford University | Stanford | California | United States | 94304 |
| 3 | Joslin Diabetes Center | Boston | Massachusetts | United States | 02215 |
| 4 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 5 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
Sponsors and Collaborators
- Sansum Diabetes Research Institute
- Harvard University
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Jaeb Center for Health Research
Investigators
- Study Chair: Eyal Dassau, PhD, Harvard University
- Study Chair: Jordan Pinsker, MD, Sansum Diabetes Research Institute
- Principal Investigator: Francis J Doyle III, PhD, Harvard University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- G200047
- UC4DK108483