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Effect of SGLT2i in Conjunction With the Artificial Pancreas on Improving the Glycemia in T1DM in the Outpatient Setting (CLASS17)

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ClinicalTrials.gov Identifier: NCT03979352
Recruitment Status : Recruiting
First Posted : June 7, 2019
Last Update Posted : November 6, 2019
Sponsor:
Collaborator:
McGill University Health Centre/Research Institute of the McGill University Health Centre
Information provided by (Responsible Party):
Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Tracking Information
First Submitted Date  ICMJE April 13, 2019
First Posted Date  ICMJE June 7, 2019
Last Update Posted Date November 6, 2019
Actual Study Start Date  ICMJE August 1, 2019
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
  • Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L compared between 4- weeks AP on empagliflozin and 4-weeks AP with placebo [ Time Frame: 20 weeks ]
    Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L compared between 4- weeks AP on empagliflozin and 4-weeks AP with placebo.
  • Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L compared between 4- weeks conventional pump therapy on empagliflozin and 4- weeks conventional pump therapy with placebo [ Time Frame: 20 weeks ]
    Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L compared between 4- weeks conventional pump therapy on empagliflozin and 4- weeks conventional pump therapy with placebo.
  • Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L on 4- weeks automated AP on empagliflozin when compared to 4-weeks conventional pump therapy on empagliflozin [ Time Frame: 20 weeks ]
    Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L on 4- weeks automated AP on empagliflozin when compared to 4-weeks conventional pump therapy on empagliflozin.
  • Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L on 4- weeks automated AP on empagliflozin when compared to 4-weeks conventional pump therapy with placebo [ Time Frame: 20 weeks ]
    Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L on 4- weeks automated AP on empagliflozin when compared to 4-weeks conventional pump therapy with placebo.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03979352 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
  • Percentage of time spent in sensor glucose target range defined as between 3.9 and 10.0 mmol/L compared between 4- weeks conventional pump therapy on empagliflozin and 4-weeks AP on empagliflozin [ Time Frame: 20 weeks ]
    Percentage of time spent in sensor glucose target range defined as between 3.9 and 10.0 mmol/L compared between 4- weeks conventional pump therapy on empagliflozin and 4-weeks AP on empagliflozin
  • Percentage of time spent in sensor glucose target range defined as between 3.9 and 10.0 mmol/L compared between 4- weeks AP on empagliflozin and 4- weeks AP with placebo [ Time Frame: 20 weeks ]
    Percentage of time spent in sensor glucose target range defined as between 3.9 and 10.0 mmol/L compared between 4- weeks AP on empagliflozin and 4- weeks AP with placebo.
  • Hypoglycemia: Percentage of time with glucose <3.9 mmol/L applied to each of the primary and secondary outcome comparator groups [ Time Frame: 20 weeks ]
    Hypoglycemia: Percentage of time with glucose <3.9 mmol/L applied to each of the primary and secondary outcome comparator groups.
  • Percentage of time spent in hypoglycemia, euglycemia and hyperglycemia [ Time Frame: 20 weeks ]
    Percentage of time spent in the different glucose sensor levels characterized by amount spent between 3.9 and 10.0 mmol/L, 3.9 and 7.8 mmol/L, above 10.0 mmol/L, above 13.9 mmol/L, above 16.7 mmol/l, below 3.9 mmol/L, below 3.3 mmol/L, below 2.8 mmol/L
  • Absolute number of hypoglycemia events I. [ Time Frame: 20 weeks ]
    Number of hypoglycemic events (> 20 minutes) below 3.3 mmol/L based on sensor glucose levels
  • Absolute number of hypoglycemia events II. [ Time Frame: 20 weeks ]
    Number of symptomatic hypoglycemic events < 3.9 mmol/l or below 3.3 mmol/l without symptoms
  • Absolute number of hypoglycemia events III. [ Time Frame: 20 weeks ]
    Number of treated hypoglycemic events
  • Statistical characteristics of glucose profile I. [ Time Frame: 20 weeks ]
    Area under the curve of hypoglycemic glucose values (below 3.9 mmol/L, 3.3 mmol/L and 2.8 mmol/L)
  • Statistical characteristics of glucose profile II. [ Time Frame: 20 weeks ]
    Standard deviation of glucose levels
  • Amount of total insulin delivery during interventions [ Time Frame: 20 weeks ]
    Total insulin delivery measured by mean of units per day
  • Change in HbA1c [ Time Frame: 20 weeks ]
    Change in HbA1c from baseline to after the first intervention and from the end of the first intervention to the end of the treatment period.
  • Mean fasting capillary ketone levels [ Time Frame: 20 weeks ]
    Mean fasting capillary ketone levels.
  • Number of episodes of diabetic ketoacidosis [ Time Frame: 20 weeks ]
    Number of episodes of diabetic ketoacidosis
  • Number of technical adverse events [ Time Frame: 20 weeks ]
    Number of events when algorithm crashes or needs to be overridden for safety reasons.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of SGLT2i in Conjunction With the Artificial Pancreas on Improving the Glycemia in T1DM in the Outpatient Setting
Official Title  ICMJE Effect of SGLT2 Inhibition on Improving the Glycemic Performance of the Single Hormone Artificial Pancreas Configuration in Type 1 Diabetes in the Outpatient Setting - A Randomized Placebo Controlled Cross-Over Multicentre Clinical Trial
Brief Summary The most advanced configurations of the Artificial Pancreas (AP) have not yet been demonstrated to sufficiently maximize time in target glycemia. One limitation is the challenge of postprandial glycemic control, which currently requires ongoing patient engagement for accurate and detailed bolus dose estimation for meals. Sodium Glucose Linked Transporter 2 Inhibition (SGLT2i) provides an additional mechanism to attenuate post-prandial glycemic excursion, and may represent a strategy that could further alleviate carbohydrate counting burden and improve the performance of AP configurations. This trial aims to compare - using a randomized, masked placebo-controlled, crossover, multicenter design - the efficacy of the SGLT2i empagliflozin 25 mg oral per day each in the setting of single-hormone automated AP and conventional insulin pump therapy on the proportion of time spent in target and in hypoglycemia each during a 4-week day-and-night period. The pilot trial aims to enroll 28 adult patients with type 1 diabetes (T1D) across 2 research sites (one in Toronto and one in Montreal) and includes a 2- week therapy optimization run-in period, 4-weeks for each of the two AP intervention arms, and a 1- week washout in between the pharmacological intervention sequences. Glucose levels will be measured by continuous glucose monitoring (G5, Dexcom Inc.). Insulin will be infused using a subcutaneous infusion pump (t-slim, Tandem Diabetes Care) and communication between pumps and the algorithm will be implemented using Android Smartphone devices and Bluetooth technology communication.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type1 Diabetes Mellitus
Intervention  ICMJE
  • Drug: empagliflozin
    Treatment with empagliflozin 25mg orally once a day
  • Device: artificial pancreas
    Insulin delivery via a closed loop single-hormone artificial pancreas system.
Study Arms  ICMJE
  • Active Comparator: Empagliflozin arm

    Participant will be treated by empagliflozin for 8 weeks. During these 8 weeks he will use artificial pancreas to deliver the insulin for 4 weeks and conventional pump therapy for remaining 4 weeks, in a random order.

    After finishing the entire arm intervention participant will undergo 7 day of washout and enters the placebo arm.

    Participant and research staff is blinded to arm assignment.

    Interventions:
    • Drug: empagliflozin
    • Device: artificial pancreas
  • Placebo Comparator: Placebo arm

    Participant will take placebo for 8 weeks. During these 8 weeks he will use artificial pancreas to deliver the insulin for 4 weeks and conventional pump therapy for remaining 4 weeks, in a random order.

    After finishing the entire arm intervention participant will undergo 7 day of washout and enters the empagliflozin arm.

    Participant and research staff is blinded to arm assignment.

    Intervention: Device: artificial pancreas
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 6, 2019)
28
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 31, 2021
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed and dated written informed consent by the date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation.
  2. Males and females ≥ 18 years of age.
  3. Clinical diagnosis of T1D for at least one year. The diagnosis of T1D is based on the investigator's clinical judgment; C peptide level and antibody determinations are not planned.
  4. Insulin pump therapy use for at least 3 months.
  5. HbA1c ≤ 10%.
  6. eGFR ≥ 60 mL/min/1.73 m² as calculated by the CKD-EPI formula.
  7. Women of child-bearing potential must be ready and able to use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly.

Exclusion Criteria:

  1. Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
  2. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
  3. Renal insufficiency (characterized at eGFR below 60 mmol/l at the beginning of the trial)
  4. History of pheochromocytoma or insulinoma
  5. Beta‐blockers at high dose (interference with glucose management).
  6. Chronic acetaminophen treatment (can interfere with glucose sensor measurements).
  7. Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding).
  8. Current use of other non-insulin adjunct anti-hyperglycemic drug or use within 30 days prior to screening.
  9. Use of loop diuretics (e.g. furosemide, due to possible interference with study drug mechanism of action).
  10. Ongoing or planned pregnancy or breastfeeding.
  11. Severe hypoglycemic episode within one month prior to Visit 1.
  12. Diabetic ketoacidosis in the last 3 months prior to Visit 1.
  13. Current use of glucocorticoid medication except low stable dose and inhaled steroids (can interfere with glucose sensor measurements).
  14. Known or suspected allergy to the trial products.
  15. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
  16. Anticipating a significant change in exercise regimen between initiation of two intervention blocks (i.e. starting or stopping an organized sport).
  17. Recent history of genital or urinary infection (<1 month prior to Visit 1) or history of recurrent urinary tract infections.
  18. Difficulty in using the artificial pancreas system following training.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Andrej Orszag 416-586-4800 ext 7625 class15@lunenfeld.ca
Contact: Nancy Cardinez, NP 416-586-4800 ext 4436 class15@lunenfeld.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03979352
Other Study ID Numbers  ICMJE CLASS 17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Study Sponsor  ICMJE Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Collaborators  ICMJE McGill University Health Centre/Research Institute of the McGill University Health Centre
Investigators  ICMJE
Principal Investigator: Bruce Perkins, MD Samuel Lunenfeld Research Institute
PRS Account Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP