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

NCT03979352 | Completed Phase 3 DMC

• 1 other identifier: CLASS 17
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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.

Conditions

Type1 Diabetes Mellitus

Keywords

Type 1 Diabetes Mellitus; Empagliflozin; Artificial Pancreas; SGLT2 inhibitor; insulin pump; closed loop

Outcome Measures

Primary Outcomes (4)

• 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 AP on empagliflozin and 4-weeks AP with placebo.

  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 compared between 4- weeks conventional pump therapy on empagliflozin and 4- weeks conventional pump therapy with placebo.

  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 on empagliflozin.

  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

  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.

  20 weeks

Secondary Outcomes (14)

• 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

  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

  20 weeks

• Hypoglycemia: Percentage of time with glucose <3.9 mmol/L applied to each of the primary and secondary outcome comparator groups

  20 weeks

• Percentage of time spent in hypoglycemia, euglycemia and hyperglycemia

  20 weeks

• Absolute number of hypoglycemia events I.

  20 weeks

Study Arms (2)

Empagliflozin arm

ACTIVE COMPARATOR

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; Device: artificial pancreas

Placebo arm

PLACEBO COMPARATOR

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

Interventions

empagliflozin DRUG

Treatment with empagliflozin 25mg orally once a day

Empagliflozin arm

artificial pancreas DEVICE

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

Empagliflozin arm; Placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent by the date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation.
• Males and females ≥ 18 years of age.
• 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.
• Insulin pump therapy use for at least 3 months.
• HbA1c ≤ 10%.
• eGFR ≥ 60 mL/min/1.73 m² as calculated by the CKD-EPI formula.
• 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.

You may not qualify if:

• Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
• Recent (\< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• Renal insufficiency (characterized at eGFR below 60 mmol/l at the beginning of the trial)
• History of pheochromocytoma or insulinoma
• Beta-blockers at high dose (interference with glucose management).
• Chronic acetaminophen treatment (can interfere with glucose sensor measurements).
• Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding).
• Current use of other non-insulin adjunct anti-hyperglycemic drug or use within 30 days prior to screening.
• Use of loop diuretics (e.g. furosemide, due to possible interference with study drug mechanism of action).
• Ongoing or planned pregnancy or breastfeeding.
• Severe hypoglycemic episode within one month prior to Visit 1.
• Diabetic ketoacidosis in the last 3 months prior to Visit 1.
• Current use of glucocorticoid medication except low stable dose and inhaled steroids (can interfere with glucose sensor measurements).
• Known or suspected allergy to the trial products.
• Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead
• McGill University Health Centre/Research Institute of the McGill University Health Centre: collaborator

Study Sites (2)

Sinai Health System

Toronto, Ontario, M5T 3L9, Canada

Location

McGill University

Montreal, Quebec, H3A 2B4, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

empagliflozin; Pancreas, Artificial

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Artificial Organs; Surgical Equipment; Equipment and Supplies

Study Officials

• Bruce Perkins, MD

  Samuel Lunenfeld Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2019
• First Posted: June 7, 2019
• Study Start: August 1, 2019
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: June 7, 2022

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)