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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

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.

Condition or disease Intervention/treatment Phase
Type1 Diabetes Mellitus Drug: empagliflozin Device: artificial pancreas Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
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.

Drug: empagliflozin
Treatment with empagliflozin 25mg orally once a day

Device: artificial pancreas
Insulin delivery via a closed loop single-hormone artificial pancreas system.

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.

Device: artificial pancreas
Insulin delivery via a closed loop single-hormone artificial pancreas system.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. Absolute number of hypoglycemia events III. [ Time Frame: 20 weeks ]
    Number of treated hypoglycemic events

  8. 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)

  9. Statistical characteristics of glucose profile II. [ Time Frame: 20 weeks ]
    Standard deviation of glucose levels

  10. Amount of total insulin delivery during interventions [ Time Frame: 20 weeks ]
    Total insulin delivery measured by mean of units per day

  11. 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.

  12. Mean fasting capillary ketone levels [ Time Frame: 20 weeks ]
    Mean fasting capillary ketone levels.

  13. Number of episodes of diabetic ketoacidosis [ Time Frame: 20 weeks ]
    Number of episodes of diabetic ketoacidosis

  14. Number of technical adverse events [ Time Frame: 20 weeks ]
    Number of events when algorithm crashes or needs to be overridden for safety reasons.



Information from the National Library of Medicine

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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:

  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.

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): NCT03979352


Contacts
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Contact: Andrej Orszag 416-586-4800 ext 7625 class15@lunenfeld.ca
Contact: Nancy Cardinez, NP 416-586-4800 ext 4436 class15@lunenfeld.ca

Locations
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Canada, Ontario
Sinai Health System Recruiting
Toronto, Ontario, Canada, M5T 3L9
Contact: Andrej Orszag    416-586-4800    class15@lunenfeld.ca   
Principal Investigator: Bruce A. Perkins, MD         
Canada, Quebec
McGill University Not yet recruiting
Montréal, Quebec, Canada, H3A 2B4
Contact: Jennifer René, RN    418- 558-0742      
Principal Investigator: Ahmad Haidar         
Sponsors and Collaborators
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
McGill University Health Centre/Research Institute of the McGill University Health Centre
Investigators
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Principal Investigator: Bruce Perkins, MD Samuel Lunenfeld Research Institute

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Responsible Party: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
ClinicalTrials.gov Identifier: NCT03979352     History of Changes
Other Study ID Numbers: CLASS 17
First Posted: June 7, 2019    Key Record Dates
Last Update Posted: November 6, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Samuel Lunenfeld Research Institute, Mount Sinai Hospital:
Type 1 Diabetes Mellitus
Empagliflozin
Artificial Pancreas
SGLT2 inhibitor
insulin pump
closed loop
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
Insulin
Empagliflozin
Pancrelipase
Pancreatin
Hypoglycemic Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action