The International Diabetes Closed Loop (iDCL) Trial: Clinical Acceptance of the Artificial Pancreas (DCLP3 Extension)

Type 1 Diabetes Mellitus Clinical Trial

Official title:

An Extension Study of t:Slim X2 With Control-IQ Technology

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03591354
• Other study ID #: DCLP3 Extension
• Secondary ID: UC4DK108483
• Status: Completed
• Phase: N/A
• Start date: January 17, 2019
• Est. completion date: March 9, 2020

Study information

• Verified date: August 2022
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 3-month extension study (DCLP3 Extension) following a primary trial (DCLP3 or NCT03563313) to assess efficacy and safety of a closed loop system (t:slim X2 with Control-IQ Technology) in a large randomized controlled trial. Upon completion of the NIH 3-month extension study, subjects will be invited to participate in a continued use phase with Control-IQ Technology, funded by Tandem Diabetes Care, until the equipment has received FDA approval for commercial use.

Description:

Participants in the 6 month primary trial (DCLP3) will be invited to continue in this 3-month extension study (DCLP3 Extension) following completion of the primary trial. The closed-loop control (CLC) Intervention Group participants from the primary trial will be randomly assigned to continue CLC or to switch to Predictive Low-Glucose Suspend (PLGS) therapy with t:slim X2 with Basal-IQ and Dexcom G6 for 3 months. The Sensor-Augmented Pump (SAP) Control Group participants from the primary trial will be assigned to CLC using t:slim X2 with Control-IQ Technology and Dexcom G6 (CGM) for 3 months. Upon completion of the extension study, subjects will be invited to participate in continued use of the Control-IQ Technology until the equipment has received FDA approval for commercial use.

This extension phase has two separate objectives:

Objective 1: Among participants who used CLC in the primary trial: the primary efficacy outcome for the randomized controlled trial (RCT) is time in target range 70-180 mg/dL measured by CGM in CLC group vs. PLGS group over 3 months. Safety outcomes also will be assessed Objective 2: Among participants who used SAP in the primary trial: the primary outcome is to obtain additional safety data. Efficacy also will be assessed as a pre-post within participant analysis

Note: Primary Trial (DCLP3) is NCT03563313

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: March 9, 2020
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

Inclusion Criteria:

1. Successful completion of the original 6-month RCT within the prior 14 days

2. 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 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.

3. For participants <18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia and able to contact the participant in case of an emergency.

4. Willingness to not use a personal CGM for the duration of the study

5. Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol

6. Willingness to use only lispro (Humalog) or aspart (Novolog), and to use no other insulin during the study.

7. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial

Exclusion Criteria

1. Concurrent use of any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas).

2. Hemophilia or any other bleeding disorder

3. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk

4. Participation in another pharmaceutical or device trial at the time of enrollment or during the study

5. Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc., Dexcom, Inc., or TypeZero Technologies, LLC, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial

Related Conditions & MeSH terms

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

Intervention

Device:
• t:slim X2 with Control-IQ Technology & Dexcom G6 CGM
Participants will use the Tandem t:slim X2 insulin pump with Control-IQ Technology & Dexcom G6 CGM for 3 months.
• t:slim X2 with Basal-IQ & Dexcom G6 CGM
Participants will use a Tandem t:slim X2 insulin pump with Basal-IQ and a study CGM (Dexcom G6) for 3 months.

Locations

Country	Name	City	State
United States	Barbara Davis Center, University of Colorado	Aurora	Colorado
United States	Harvard University (Joslin Diabetes Center)	Boston	Massachusetts
United States	University of Virginia Center for Diabetes Technology	Charlottesville	Virginia
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 (6)

Lead Sponsor	Collaborator
University of Virginia	DexCom, Inc., Jaeb Center for Health Research, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Roche Diagnostics, Tandem Diabetes Care, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	13 weeks
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).	13 weeks
Other	Worsening of HbA1c From Randomization to 13 Weeks by >0.5%	Worsening of HbA1c from randomization to 13 weeks by >0.5%.	13 weeks
Other	Serious Adverse Events With a Possible or Greater Relationship to a Study Device (Including Anticipated and Unanticipated Adverse Device Effects)	Serious adverse events with a possible or greater relationship to a study device (including anticipated and unanticipated adverse device effects).	13 weeks
Other	Adverse Device Effects (ADE) That do Not Meet Criteria for SAE	Adverse device effects (ADE) that do not meet criteria for SAE.	13 weeks
Other	Other Serious Adverse Events Not Related to a Study Device	Other serious adverse events not related to a study device.	13 weeks
Other	Severe Hypoglycemic Events	Number of Severe Hypoglycemic events over initial 13 weeks of trial	13 weeks
Other	Severe Hypoglycemic Event Rate Per 100 Person-years	Number of severe hypoglycemic events per 100 person-years over initial 13 weeks of trial	13 weeks
Other	Diabetic Ketoacidosis (DKA) Events	Number of DKA events over initial 13 weeks of trial	13 weeks
Other	Diabetic Ketoacidosis (DKA) Event Rate Per 100 Person-years	Number of DKA events per 100 person-years over initial 13 weeks	13 weeks
Other	Any Adverse Event Rate Per 100 Person-years	Number of adverse events per 100 person-years over initial 13 weeks	13 weeks
Other	Time in Target Range From Months 4-12	CGM time in target range 70-180mg/dL for all participants using CLC from Months 4-12.	Months 4-12
Other	CGM Time Above 180 From Months 4-12	CGM-measured % above 180mg/dL from Months 4-12	Months 4-12
Other	CGM Mean Glucose From Months 4-12	CGM-measured mean glucose from Months 4-12	Months 4-12
Other	CGM Time Below 70 From Months 4-12	CGM-measured % below 70 mg/dL from Months 4-12	Months 4-12
Other	CGM Time Below 54 From Months 4-12	CGM-measured % time below 54mg/dL from Months 4-12	Months 4-12
Other	CGM Time in Range 70-140 mg/dL From Months 4-12	CGM-measured % time in range 70-140mg/dL from Months 4-12	Months 4-12
Other	Coefficient of Variation From Months 4-12	CGM measured glucose variability measured with the coefficient of variation from Months 4-12	Months 4-12
Other	Standard Deviation From Months 4-12	CGM measured glucose variability measured with the standard deviation (SD) from Months 4-12	Months 4-12
Other	CGM Time Below 60 From Months 4-12	CGM-measured % below 60mg/dL from Months 4-12	Months 4-12
Other	LBGI From Months 4-12	LBGI from Months 4-12. 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)	Months 4-12
Other	HBGI From Months 4-12	HBGI from Months 4-12. 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)	Months 4-12
Other	CGM Hypoglycemia Events From Months 4-12	CGM-measured events of at least 15 consecutive minutes <70mg/dL from Months 4-12	Months 4-12
Other	CGM Time >250 From Months 4-12	CGM-measured % time >250 mg/dL from Months 4-12	Months 4-12
Other	CGM Time >300 From Months 4-12	CGM-measured % time >300 mg/dL from Months 4-12	Months 4-12
Other	HbA1c at Month 6	HbA1c measured at Month 6 of this extension study	Month 6 of study
Other	HbA1c at Month 9	HbA1c measured at month 9 of this extension study	Month 9 of study
Other	HbA1c at Month 12	HbA1c measured at Month 12 of this extension study	Month 12 of study
Other	Ketone Events Defined as Days With Ketone Level >1.0 mmol/L From Months 4-12	Ketone Events Defined as Number of Days with at least one Ketone Level >1.0 mmol/L from Months 4-12	Months 4-12
Other	CGM-measured Hypoglycemia Events (>15 Minutes With Glucose Concentration <54mg/dL) From Months 4-12	CGM-measured Hypoglycemia Events (>15 minutes with glucose concentration <54mg/dL) from Months 4-12 measured as a rate per week.	Months 4-12
Other	CGM-measured Hyperglycemic Events From Months 4-12	CGM-measured Hyperglycemic Events (>15 consecutive minutes with CGM glucose >300mg/dL) from Months 4-12	Months 4-12
Other	Number of Severe Hypoglycemic Events From Months 4-12	Number of Severe Hypoglycemic Events from Months 4-12.	Months 4-12
Other	Number of Diabetic Ketoacidosis (DKA) Events From Months 4-12	Number of Diabetic Ketoacidosis (DKA) events from Months 4-12.	Months 4-12
Other	Other Serious Adverse Events Not Related to a Study Device From Months 4-12	Other Serious Adverse Events Not Related to a Study Device from Months 4-12.	Months 4-12
Other	Any Adverse Event Rate Per 100 Person-years From Months 4-12	Any Adverse Event Rate per 100 person-years from Months 4-12.	Months 4-12
Primary	Time in Target Range	The primary exploratory outcome is time in target range 70-180 mg/dL measured by CGM comparing the randomized groups CLC vs PLGS. Results from SAP to CLC group is also included here without the primary intention of comparing to CLC vs PLGS groups.	13 weeks
Secondary	CGM Time Above 180	CGM-measured % above 180 mg/dL	13 weeks
Secondary	CGM Mean Glucose	CGM-measured mean glucose	13 weeks
Secondary	CGM Time Below 70	CGM-measured % below 70 mg/dL	13 weeks
Secondary	CGM Time Below 54	CGM-measured % below 54 mg/dL	13 weeks
Secondary	CGM Time in Range 70-140 mg/dL	CGM-measured % in range 70-140 mg/dL	13 weeks
Secondary	Coefficient of Variation	CGM measured glucose variability measured with the coefficient of variation (CV)	13 weeks
Secondary	Standard Deviation	CGM measured glucose variability measured with the standard deviation (SD)	13 weeks
Secondary	CGM Time Below 60	CGM-measured % below 60 mg/dL	13 weeks
Secondary	LBGI	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)	13 weeks
Secondary	CGM Hypoglycemia Events	CGM-measured events of at least 15 consecutive minutes <70 mg/dL	13 weeks
Secondary	CGM Time >250	CGM-measured % >250 mg/dL	13 weeks
Secondary	CGM Time >300	CGM-measured % >300 mg/dL	13 weeks
Secondary	HBGI	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)	13 weeks
Secondary	HbA1c at 13 Weeks	HbA1c at 13 weeks.	13 weeks
Secondary	HbA1c <7.0% at 13 Weeks	HbA1c <7.0% at 13 weeks.	13 weeks
Secondary	HbA1c <7.5% at 13 Weeks	HbA1c <7.5% at 13 weeks.	13 weeks
Secondary	HbA1c Change From Baseline to 13 Weeks >0.5%	HbA1c change from baseline to 13 weeks >0.5%.	13 weeks
Secondary	HbA1c Change From Baseline to 13 Weeks >1.0%	HbA1c change from baseline to 13 weeks >1.0%.	13 weeks
Secondary	HbA1c Relative Change From Baseline to 13 Weeks >10%	HbA1c relative change from baseline to 13 weeks >10%.	13 weeks
Secondary	HbA1c Change From Baseline to 13 Weeks >1.0% or HbA1C <7.0% at 13 Weeks	HbA1c change from baseline to 13 weeks >1.0% or HbA1c <7.0% at 13 weeks.	13 weeks
Secondary	HFS-II Adult	Fear of Hypoglycemia Survey (HFS-II) total score and 3 sub scales (5 point scale with never to almost always); For adults, teens and parents items on this survey are rated on a 5 point Likert scale from never (0) to almost always (4). The survey is scored by summing item responses. Fear of Hypoglycemia Survey (HFS-II) for adults has a total score that is summed from the two subscale scores (33 items) and ranges from 0 to 132 with higher scores indicating greater degrees of fear of hypoglycemia.	13 weeks
Secondary	HFS-II Teen	Fear of Hypoglycemia Survey (HFS-II) total score and 3 sub scales (5 point scale with never to almost always); For adults, teens and parents items on this survey are rated on a 5 point Likert scale from never (0) to almost always (4). The survey is scored by summing item responses.The teen survey has a total of 25 items and the range of Total scores is 0 to 100.	13 weeks
Secondary	HFS-II Parents	Fear of Hypoglycemia Survey (HFS-II) total score and 3 sub scales (5 point scale with never to almost always); For adults, teens and parents items on this survey are rated on a 5 point Likert scale from never (0) to almost always (4). The parent version of the survey has a total of 26 items with Total scores that range from 0 to 108.	13 weeks
Secondary	Hyperglycemia Avoidance Scale	Hyperglycemia Avoidance Scale total score is the sum of 21 items rated on a 4 point Likert scale from 0 (never) to 4 (almost always) and ranges from 0 to 84 with a higher score indicating greater degrees of avoiding hyperglycemia.	13 weeks
Secondary	Diabetes Distress Scale	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	Hypoglycemia Confidence Scale	Hypoglycemia Confidence Scale has 9 items which are self-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	Clarke Hypoglycemia Awareness Scores	Clarke Hypoglycemia Awareness Scores (0-7 score with higher scores associated with impaired awareness)	13 weeks
Secondary	INSPIRE Survey Scores- Adults	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.	13 weeks
Secondary	INSPIRE Survey Scores- Teens	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 Teens/Adolescents survey has 17 items.	13 weeks
Secondary	INSPIRE Survey Scores- Parents	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 Parent survey has 21 items.	13 weeks
Secondary	System Usability Scores (SUS)	System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicating better perceived usability	13 weeks
Secondary	Technology Acceptance Questionnaire	Technology Acceptance Survey measures the user's perceptions regarding the burdens and the barriers associated with a technology with a higher score indicates increased technology acceptance. There total score uses 37 items with items are rated on a 5 point scale ranging from 1 (strongly disagree) to 5 (strongly agree) for total score range of 37-185.	13 weeks
Secondary	Total Daily Insulin	Total Daily Insulin (units/kg)	13 weeks
Secondary	Basal:Bolus Insulin Ratio	Basal:Bolus Insulin Ratio.	13 weeks
Secondary	Weight	Weight (kg)	13 weeks
Secondary	BMI	Body Mass Index (BMI) kg/m2	13 weeks