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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04436796
Recruitment Status : Recruiting
First Posted : June 18, 2020
Last Update Posted : August 6, 2020
Sponsor:
Collaborators:
Harvard University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Jaeb Center for Health Research
Information provided by (Responsible Party):
Sansum Diabetes Research Institute

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
Type 1 Diabetes Device: interoperable Artificial Pancreas System (iAPS) Other: Sensor-Augmented Pump (SAP)/Predictive Low Glucose Suspend (PLGS) Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 5, 2020
Estimated Primary Completion Date : July 15, 2021
Estimated Study Completion Date : September 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

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.




Primary Outcome Measures :
  1. CGM Time in Range 70-180 mg/dL [ Time Frame: 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

  2. Non-inferiority for CGM time <54 mg/dL [ Time Frame: 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 :
  1. CGM Mean Glucose [ Time Frame: 13 weeks ]
    CGM-measured mean glucose (mg/dL)

  2. CGM Time > 180 [ Time Frame: 13 weeks ]
    CGM time > 180 mg/dL

  3. CGM Time > 250 [ Time Frame: 13 weeks ]
    CGM time > 250 mg/dL

  4. CGM Time < 70 [ Time Frame: 13 weeks ]
    CGM time < 70 mg/dL

  5. CGM Time < 54 (Superiority) [ Time Frame: 13 weeks ]
    CGM time < 54 mg/dL (Superiority)

  6. Coefficient of Variation [ Time Frame: 13 weeks ]
    CGM measured glucose variability measured with the coefficient of variation (CV)

  7. CGM Time in Range 70-140 mg/dL [ Time Frame: 13 weeks ]
    CGM-measured % in range 70-140 mg/dL

  8. Standard Deviation [ Time Frame: 13 weeks ]
    CGM measured glucose variability measured with the standard deviation (SD)

  9. CGM Time < 60 [ Time Frame: 13 weeks ]
    CGM time < 60 mg/dL

  10. LBGI [ Time Frame: 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)

  11. CGM Hypoglycemia Events [ Time Frame: 13 weeks ]
    CGM-measured events of at least 15 consecutive minutes <70mg/dL per week

  12. CGM Time > 300 [ Time Frame: 13 weeks ]
    CGM time > 300 mg/dL

  13. HBGI [ Time Frame: 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)

  14. HbA1c at 13 weeks [ Time Frame: 13 weeks ]
    Hemiglobin A1c measured after completing each study arm

  15. Number of Participants With HbA1c <7.0% at 13 weeks [ Time Frame: 13 weeks ]
    Number of participants HbA1c <7.0% after completing each study arm

  16. Number of Participants With HbA1c <7.5% at 13 weeks [ Time Frame: 3 months ]
    Number of participants HbA1c <7.5% after completing each study arm

  17. HbA1c improvement from baseline to 13 weeks >0.5% [ Time Frame: 13 weeks ]
    HbA1c improvement from baseline to 13 weeks >0.5% after completing each study arm

  18. HbA1c improvement from baseline to 13 weeks >1% [ Time Frame: 13 weeks ]
    HbA1c improvement from baseline to 13 weeks >1% after completing each study arm

  19. HbA1c relative improvement from baseline to 13 weeks >10% [ Time Frame: 13 weeks ]
    HbA1c relative improvement from baseline to 3 months >10% after completion of each study arm

  20. Number of Participants With HbA1c Improvement From Baseline to 3 months >1.0% or HbA1c <7.0% after 3 months [ Time Frame: 13 weeks ]
    HbA1c improvement from baseline to 13 weeks >1.0% or HbA1c <7.0% after 13 weeks in each arm

  21. Diabetes Distress Scale at 13 weeks - total score and 4 subscales: Emotional burden, Physician-related distress, Regimen-related distress, Interpersonal distress [ Time Frame: 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.

  22. Glucose Monitoring Satisfaction Survey [ Time Frame: 13 weeks ]
    Satisfaction, burden, and total scores

  23. Hypoglycemia Confidence Scale [ Time Frame: 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.

  24. Diabetes Technology Attitudes Survey [ Time Frame: 13 weeks ]
    Diabetes Technology Attitudes Survey

  25. INSPIRE survey scores - following study system period only [ Time Frame: 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.

  26. SUS survey scores - following study system period [ Time Frame: 13 weeks ]
    System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicate better perceived usability

  27. Total Daily Insulin [ Time Frame: 13 weeks ]
    Total Daily Insulin (units)

  28. Basal: bolus insulin ratio [ Time Frame: 13 weeks ]
    Basal: bolus insulin ratio

  29. Weight [ Time Frame: 13 weeks ]
    Weight (kg)

  30. BMI [ Time Frame: 13 weeks ]
    Body Mass Index (BMI) kg/m^2


Other Outcome Measures:
  1. CGM metrics by time of day [ Time Frame: 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).

  2. Number of Participants With Severe Hypoglycemia (Per Protocol) [ Time Frame: 13 weeks ]
    Severe hypoglycemia (per protocol)

  3. Number of Participants With Diabetic Ketoacidosis (Per Protocol) [ Time Frame: 13 weeks ]
    Diabetic ketoacidosis (per protocol)

  4. Ketone Events Defined as Day With Ketone Level >1.0 mmol/L [ Time Frame: 13 weeks ]
    Ketone events defined as day with ketone level >1.0 mmol/L

  5. CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL) [ Time Frame: 3 months ]
    CGM-measured hypoglycemic events (>15 minutes with glucose concentration <54 mg/dL) in each arm.

  6. CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL) [ Time Frame: 3 months ]
    CGM-measured hyperglycemic events (>15 minutes with glucose concentration >300 mg/dL) in each arm.

  7. BG-measured Hypoglycemic Events (One BG Record <54 mg/dL [ Time Frame: 13 weeks ]
    BG-measured Hypoglycemic Events (One BG Record <54 mg/dL

  8. Worsening of HbA1c From Baseline to 26 Weeks by >0.5% [ Time Frame: 13 weeks ]
    Worsening of HbA1c from baseline to 26 weeks by >0.5%

  9. Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) [ Time Frame: 13 weeks ]
    Other serious adverse events (SAE) and serious adverse device events (SADE)

  10. Adverse Device Effects (ADE) [ Time Frame: 13 weeks ]
    Adverse device effects (ADE)

  11. Unanticipated Adverse Device Effects (UADE) [ Time Frame: 13 weeks ]
    Unanticipated adverse device effects (UADE)

  12. Number of Participants With SH Events [ Time Frame: 13 weeks ]
    For this outcome, mean +/- SD or summary statistics appropriate to the distribution will be tabulated by treatment group

  13. SH Event Rate Per 100 Person-years [ Time Frame: 13 weeks ]
    For this outcome, severe hypoglycemia event rate per 100 person-years will be calculated as a rate.

  14. Number of Participants With DKA Events [ Time Frame: 13 weeks ]
    For this outcome, number of participants with diabetic ketoacidosis (DKA) will be tabulated.

  15. DKA Event Rate Per 100 Person-years [ Time Frame: 13 weeks ]
    For this outcome, the diabetic ketoacidosis event rate per 100 person-years will be calculated as a rate.

  16. Any Adverse Event Rate Per 100 Person-years [ Time Frame: 13 weeks ]
    For this outcome, the adverse event rate per 100 person-years calculated as a rate.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04436796


Contacts
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Contact: John Lum (813) 975-8690 jlum@jaeb.org

Locations
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United States, California
Sansum Diabetes Research Institute Recruiting
Santa Barbara, California, United States, 93105
Contact: Mei Mei Church         
Principal Investigator: Jordan E Pinsker, MD         
Stanford University Not yet recruiting
Stanford, California, United States, 94304
Contact: Liana Hsu         
Principal Investigator: Bruce Buckingham, MD         
United States, Massachusetts
Joslin Diabetes Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Emily Freiner         
Principal Investigator: Lori Laffel, MD         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Shelly McCrady-Spitzer         
Principal Investigator: Yogish Kudva, MBBS         
United States, New York
Icahn School of Medicine at Mount Sinai Not yet recruiting
New York, New York, United States, 10029
Contact: Selassie Ogyaadu         
Principal Investigator: Carol Levy, MD         
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
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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
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Responsible Party: Sansum Diabetes Research Institute
ClinicalTrials.gov Identifier: NCT04436796    
Other Study ID Numbers: G200047
UC4DK108483 ( U.S. NIH Grant/Contract )
First Posted: June 18, 2020    Key Record Dates
Last Update Posted: August 6, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Sansum Diabetes Research Institute:
Artificial Pancreas
Automated Insulin Delivery
Closed Loop Control
Continuous Glucose Monitor (CGM)
interoperable Artificial Pancreas System (iAPS)
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Pancrelipase
Gastrointestinal Agents