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

Type 1 Diabetes Clinical Trial

— DCLP4  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04436796
• Other study ID #: G200047
• Secondary ID: UC4DK108483
• Status: Completed
• Phase: N/A
• Start date: August 5, 2020
• Est. completion date: May 10, 2021

Study information

• Verified date: November 2022
• Source: Sansum Diabetes Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: May 10, 2021
• Est. primary completion date: May 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

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.

Other:
• Sensor-Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS)
Use of personal pump with study CGM & glucometer at home for 13 weeks.

Locations

Country	Name	City	State
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Sansum Diabetes Research Institute	Santa Barbara	California
United States	Stanford University	Stanford	California

Sponsors (4)

Lead Sponsor	Collaborator
Sansum Diabetes Research Institute	Harvard University, Jaeb Center for Health Research, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Compari — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Number of Participants With Severe Hypoglycemia (Per Protocol)	Severe hypoglycemia (per protocol)	13 weeks
Other	Number of Participants With Diabetic Ketoacidosis (Per Protocol)	Diabetic ketoacidosis (per protocol)	13 weeks
Other	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
Other	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
Other	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
Other	BG-measured Hypoglycemic Events (One BG Record <54 mg/dL	BG-measured Hypoglycemic Events (One BG Record <54 mg/dL	13 weeks
Other	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	Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE)	Other serious adverse events (SAE) and serious adverse device events (SADE)	13 weeks
Other	Adverse Device Effects (ADE)	Adverse device effects (ADE)	13 weeks
Other	Unanticipated Adverse Device Effects (UADE)	Unanticipated adverse device effects (UADE)	13 weeks
Other	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
Other	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
Other	Number of Participants With DKA Events	For this outcome, number of participants with diabetic ketoacidosis (DKA) will be tabulated.	13 weeks
Other	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
Other	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
Primary	Percent CGM Time in Range 70-180 mg/dL	This results shown is mean percent time in range 70-180 mg/dL.	13 weeks
Primary	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	CGM Mean Glucose	CGM-measured mean glucose (mg/dL)	13 weeks
Secondary	CGM Time > 180	CGM time > 180 mg/dL	13 weeks
Secondary	CGM Time > 250	CGM time > 250 mg/dL	13 weeks
Secondary	CGM Time < 70	CGM time < 70 mg/dL	13 weeks
Secondary	CGM Time < 54 (Superiority)	CGM time < 54 mg/dL (Superiority)	13 weeks
Secondary	Coefficient of Variation	CGM measured glucose variability measured with the coefficient of variation (CV)	13 weeks
Secondary	CGM Time in Range 70-140 mg/dL	CGM-measured % in range 70-140 mg/dL	13 weeks
Secondary	Standard Deviation	CGM measured glucose variability measured with the standard deviation (SD)	13 weeks
Secondary	CGM Time < 60	CGM time < 60 mg/dL	13 weeks
Secondary	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
Secondary	CGM Time > 300	CGM time > 300 mg/dL	13 weeks
Secondary	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
Secondary	HbA1c at 13 Weeks	Hemiglobin A1c measured after completing each study arm	13 weeks
Secondary	Number of Participants With HbA1c <7.0% at 13 Weeks	Number of participants HbA1c <7.0% after completing each study arm	13 weeks
Secondary	Number of Participants With HbA1c <7.5% at 13 Weeks	Number of participants HbA1c <7.5% after completing each study arm	3 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Total Daily Insulin	Total Daily Insulin (units)	13 weeks
Secondary	Basal: Bolus Insulin Ratio	Basal: bolus insulin ratio	13 weeks