Clinical trial NCT04436796: The International Diabetes Closed Loop (iDCL) Trial: Protocol 4
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: Artificial Pancreas
Automated Insulin Delivery
Closed Loop Control
Continuous Glucose Monitor (CGM)
interoperable Artificial Pancreas System (iAPS)
Lead sponsor: Sansum Diabetes Research Institute
Sponsor class: OTHER
Collaborators: name: Harvard University
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Jaeb Center for Health Research
First posted: 2020-06-18
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

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
* 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

Primary outcomes:
measure: Percent CGM Time in Range 70-180 mg/dL
timeFrame: 13 weeks
measure: Non-inferiority for CGM Time <54 mg/dL
timeFrame: 13 weeks
Secondary outcomes:
measure: CGM Mean Glucose
timeFrame: 13 weeks
measure: CGM Time > 180
timeFrame: 13 weeks
measure: CGM Time > 250
timeFrame: 13 weeks
measure: CGM Time < 70
timeFrame: 13 weeks
measure: CGM Time < 54 (Superiority)
timeFrame: 13 weeks
measure: Coefficient of Variation
timeFrame: 13 weeks
measure: CGM Time in Range 70-140 mg/dL
timeFrame: 13 weeks
measure: Standard Deviation
timeFrame: 13 weeks
measure: CGM Time < 60
timeFrame: 13 weeks
measure: LBGI
timeFrame: 13 weeks
measure: CGM Time > 300
timeFrame: 13 weeks
measure: HBGI
timeFrame: 13 weeks
measure: HbA1c at 13 Weeks
timeFrame: 13 weeks
measure: Number of Participants With HbA1c <7.0% at 13 Weeks
timeFrame: 13 weeks
measure: Number of Participants With HbA1c <7.5% at 13 Weeks
timeFrame: 3 months
measure: Diabetes Distress Scale at 13 Weeks - Total Score
timeFrame: 13 weeks
measure: Glucose Monitoring Satisfaction Survey (Total Scale)
timeFrame: 13 weeks
measure: Hypoglycemia Confidence Scale
timeFrame: 13 weeks
measure: INSPIRE Survey Scores - Following Study System Period Only
timeFrame: 13 weeks
measure: SUS Survey Scores - Following Study System Period
timeFrame: 13 weeks
measure: Total Daily Insulin
timeFrame: 13 weeks
measure: Basal: Bolus Insulin Ratio
timeFrame: 13 weeks
Other outcomes:
measure: CGM Metrics by Time of Day
timeFrame: 13 weeks
measure: Number of Participants With Severe Hypoglycemia (Per Protocol)
timeFrame: 13 weeks
measure: Number of Participants With Diabetic Ketoacidosis (Per Protocol)
timeFrame: 13 weeks
measure: Ketone Events Defined as Day With Ketone Level >1.0 mmol/L
timeFrame: 13 weeks
measure: CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL)
timeFrame: 3 months
measure: CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL)
timeFrame: 3 months
measure: BG-measured Hypoglycemic Events (One BG Record <54 mg/dL
timeFrame: 13 weeks
measure: Worsening of HbA1c From Baseline to 26 Weeks by >0.5%
timeFrame: 13 weeks
measure: Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE)
timeFrame: 13 weeks
measure: Adverse Device Effects (ADE)
timeFrame: 13 weeks
measure: Unanticipated Adverse Device Effects (UADE)
timeFrame: 13 weeks
measure: Number of Participants With SH Events
timeFrame: 13 weeks
measure: SH Event Rate Per 100 Person-years
timeFrame: 13 weeks
measure: Number of Participants With DKA Events
timeFrame: 13 weeks
measure: DKA Event Rate Per 100 Person-years
timeFrame: 13 weeks
measure: Any Adverse Event Rate Per 100 Person-years
timeFrame: 13 weeks
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: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Harvard University
name: Eyal Dassau, PhD
role: STUDY_CHAIR
affiliation: Sansum Diabetes Research Institute
name: Jordan Pinsker, MD
role: STUDY_CHAIR
affiliation: Harvard University
name: Francis J Doyle III, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.