The International Diabetes Closed Loop (iDCL) Trial: Protocol 4 (DCLP4)

The International Diabetes Closed Loop (iDCL) Trial: A Randomized Crossover Comparison of Adaptive Model Predictive Control (MPC) Artificial Pancreas Versus Sensor Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS) in the Outpatient Setting in Type 1 Diabetes (DCLP4)

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: interoperable Artificial Pancreas System (iAPS); Other: Sensor-Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS)

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 Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Barbara, California, United States, 93105
      • Sansum Diabetes Research Institute
    • Stanford, California, United States, 94304
      • Stanford University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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
• Using an insulin pump for at least 3 months (which may include use of automated features)
• Familiarity and use of a carbohydrate ratio for meal boluses
• Age ≥18.0 years old
• 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.
• If using a personal CGM, willingness to use a Dexcom G6 CGM and discontinue personal CGM use during the study
• 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
• 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
• 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
• 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.
• Two or more episodes of DKA requiring an emergency room visit or hospitalization in the past 6 months
• Two or more episodes of severe hypoglycemia with seizure or loss of consciousness in the last 6 months
• Hemophilia or any other bleeding disorder
• 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
• Participation in another pharmaceutical or device trial at the time of enrollment or during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent CGM Time in Range 70-180 mg/dL	This results shown is mean percent time in range 70-180 mg/dL.	13 weeks
Non-inferiority for CGM Time <54 mg/dL	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	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGM Time in Range 70-140 mg/dL	CGM-measured % in range 70-140 mg/dL	13 weeks
Coefficient of Variation	CGM measured glucose variability measured with the coefficient of variation (CV)	13 weeks
Standard Deviation	CGM measured glucose variability measured with the standard deviation (SD)	13 weeks
CGM Mean Glucose	CGM-measured mean glucose (mg/dL)	13 weeks
CGM Time > 180	CGM time > 180 mg/dL	13 weeks
CGM Time > 250	CGM time > 250 mg/dL	13 weeks
CGM Time < 70	CGM time < 70 mg/dL	13 weeks
CGM Time < 54 (Superiority)	CGM time < 54 mg/dL (Superiority)	13 weeks
CGM Time < 60	CGM time < 60 mg/dL	13 weeks
LBGI	Low blood glucose index (LBGI) by CGM with higher index indicating higher risk of hypoglycemia. LBGI ≤ 1.1 is associated with minimal risk of hypoglycemia, 1.1 < LBGI ≤ 2.5 is associated with a low risk of hypoglycemia, 2.5 < LBGI ≤ 5.0 is associated with a moderate risk of hypoglycemia, and LBGI > 5.0 is associated with high risk of hypoglycemia.	13 weeks
CGM Time > 300	CGM time > 300 mg/dL	13 weeks
HBGI	High Blood Glucose Index (HBGI) is a measure of Hyperglycemic Risk based on frequency and severity of hyperglycemic events. HBGI < 4.5 is associated with lower risk of hyperglycemia, 4.5 < HBGI < 9 is associated with a moderate risk of hyperglycemia and HBGI > 9 is associated with high risk of hyperglycemia	13 weeks
HbA1c at 13 Weeks	Hemiglobin A1c measured after completing each study arm	13 weeks
Number of Participants With HbA1c <7.0% at 13 Weeks	Number of participants HbA1c <7.0% after completing each study arm	13 weeks
Number of Participants With HbA1c <7.5% at 13 Weeks	Number of participants HbA1c <7.5% after completing each study arm	3 months
Diabetes Distress Scale at 13 Weeks - Total Score	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.	13 weeks
Glucose Monitoring Satisfaction Survey (Total Scale)	The GMSS for Type 1 Diabetes contains four subscales as well as a total scale. For this measure, total scale is reported. To calculate the total scale (higher scores indicate greater satisfaction): Mean of all items 1-15 (reverse code items: 2-7, 9, 11-13, and 15) which are all scored on a 5 point scale (1-5) (Minimum Total Scale Score is 1, Maximum Total Scale Score is 5)	13 weeks
Hypoglycemia Confidence Scale	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.	13 weeks
INSPIRE Survey Scores - Following Study System Period Only	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.	13 weeks
SUS Survey Scores - Following Study System Period	System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicate better perceived usability	13 weeks
Total Daily Insulin	Total Daily Insulin (units)	13 weeks
Basal: Bolus Insulin Ratio	Basal: bolus insulin ratio	13 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGM Metrics by Time of Day	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).	13 weeks
Number of Participants With Severe Hypoglycemia (Per Protocol)	Severe hypoglycemia (per protocol)	13 weeks
Number of Participants With Diabetic Ketoacidosis (Per Protocol)	Diabetic ketoacidosis (per protocol)	13 weeks
Ketone Events Defined as Day With Ketone Level >1.0 mmol/L	Ketone events defined as day with ketone level >1.0 mmol/L	13 weeks
CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL)	CGM-measured hypoglycemic events (>15 minutes with glucose concentration <54 mg/dL) in each arm.	3 months
CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL)	CGM-measured hyperglycemic events (>15 minutes with glucose concentration >300 mg/dL) in each arm.	3 months
BG-measured Hypoglycemic Events (One BG Record <54 mg/dL	BG-measured Hypoglycemic Events (One BG Record <54 mg/dL	13 weeks
Worsening of HbA1c From Baseline to 26 Weeks by >0.5%	Worsening of HbA1c from baseline to 26 weeks by >0.5%	13 weeks
Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE)	Other serious adverse events (SAE) and serious adverse device events (SADE)	13 weeks
Adverse Device Effects (ADE)	Adverse device effects (ADE)	13 weeks
Unanticipated Adverse Device Effects (UADE)	Unanticipated adverse device effects (UADE)	13 weeks
Number of Participants With SH Events	For this outcome, mean +/- SD or summary statistics appropriate to the distribution will be tabulated by treatment group	13 weeks
SH Event Rate Per 100 Person-years	For this outcome, severe hypoglycemia event rate per 100 person-years will be calculated as a rate.	13 weeks
Number of Participants With DKA Events	For this outcome, number of participants with diabetic ketoacidosis (DKA) will be tabulated.	13 weeks
DKA Event Rate Per 100 Person-years	For this outcome, the diabetic ketoacidosis event rate per 100 person-years will be calculated as a rate.	13 weeks
Any Adverse Event Rate Per 100 Person-years	For this outcome, the adverse event rate per 100 person-years calculated as a rate.	13 weeks

Collaborators and Investigators

• Sponsor: Sansum Diabetes Research Institute
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Harvard University; Jaeb Center for Health Research
• Investigators: Study Chair: Jordan Pinsker, MD, Sansum Diabetes Research Institute; Study Chair: Eyal Dassau, PhD, Harvard University; Principal Investigator: Francis J Doyle III, PhD, Harvard University

Publications and helpful links

General Publications

• Pinsker JE, Dassau E, Deshpande S, Raghinaru D, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Church MM, Desrochers H, Ekhlaspour L, Kaur RJ, Levister C, Shi D, Lum JW, Kollman C, Doyle FJ; iDCL Trial Research Group. Outpatient Randomized Crossover Comparison of Zone Model Predictive Control Automated Insulin Delivery with Weekly Data Driven Adaptation Versus Sensor-Augmented Pump: Results from the International Diabetes Closed-Loop Trial 4. Diabetes Technol Ther. 2022 Sep;24(9):635-642. doi: 10.1089/dia.2022.0084. Epub 2022 Jun 2.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2020
• Primary Completion (Actual): May 10, 2021
• Study Completion (Actual): May 10, 2021

Study Registration Dates

• First Submitted: June 16, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: November 8, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Continuous Glucose Monitor (CGM); Artificial Pancreas; Closed Loop Control; Automated Insulin Delivery; interoperable Artificial Pancreas System (iAPS)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Gastrointestinal Agents; Pancrelipase
• Other Study ID Numbers: G200047; UC4DK108483 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NIH's Data Sharing Policy on sharing research resources for research purposes to the scientific community will be followed. Data will be stored in a Data Archive Database includes CGM-insulin delivery time series & boluses, will be deidentified & retrievable only by subject ID number. Individual patterns of demographic & insulin treatment parameters leave open a remote possibility of deductive disclosure of subjects with unusual characteristics. Thus, data will be made available only under a Data-Sharing Agreement that includes: (1) a commitment to using the data only for research purposes & not to identify participants; (2) a commitment to securing the data using appropriate computer technology; & (3) a commitment to destroying or returning the data after analyses are completed.
• IPD Sharing Time Frame: The dataset from each iDCL protocol will be made public after publication of all manuscripts written by the study group using the dataset and any regulatory submission/completion of review by the regulatory agency, but no later than 3 years after the completion of the protocol even if additional manuscripts or regulatory submissions are planned.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes