Alleviating Carbohydrate-Counting Burden in T1DM Using Artificial Pancreas and Empagliflozin

Alleviating Carbohydrate-Counting Burden in Type 1 Diabetes Using Artificial Pancreas and Sodium Glucose-Linked Transporter 2 Inhibition: A Randomized Open-Label Crossover Trial.

Sponsors

Lead Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Collaborator: Canadian Diabetes Association
Institut de Recherches Cliniques de Montreal
McGill University Health Centre/Research Institute of the McGill University Health Centre

Source Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Brief Summary

One of the challenges in the design of the artificial pancreas (AP) is preventing postprandial hyperglycemia. Beyond algorithmic solutions, one countermeasure to postprandial hyperglycemia that may enhance performance of the AP is the use of adjunctive-to-insulin medications such as those in the Sodium Glucose-Linked Transporter 2 inhibitor class. This study evaluates whether use of oral empagliflozin on the background of single-hormone AP can improve postprandial blood glucose control. The investigators will test this hypothesis in a cross-over trial design by comparing open-label empagliflozin versus placebo in the setting of AP on separate study days that involve carbohydrate counting, simple meal announcement and no meal announcement strategies.

Detailed Description

Empagliflozin is a novel anti-diabetic medication and has been approved in Canada. The labelled indication for use of empagliflozin in clinical practice is as an adjunct therapy to diet and exercise to improve glycemic control in adult patients with type 2 diabetes. The investigators are proposing to use the medication as an adjunct anti-diabetic therapy in individuals with type 1 diabetes and would like to examine whether empagliflozin can alleviate need for carb-counting by eliminating post-prandial hyperglycemia in a setting of an artificial pancreas (AP).

The study is designed as a randomized open-label, crossover non-inferiority trial comparing empagliflozin 25 mg oral daily in the setting of the single-hormone AP to single-hormone AP without empagliflozin in adults with type 1 diabetes. The duration of the study for each of the participants is about 3-9 weeks and during this time three different meal announcement strategies for AP will be used, on and off empagliflozin treatment.

Overall Status Recruiting
Start Date May 15, 2018
Completion Date December 31, 2019
Primary Completion Date December 31, 2019
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Comparison of mean glucose levels between artificial pancreas (AP) with empagliflozin with no-meal announcement meal approach strategy and AP without empagliflozin with carb-counting meal approach strategy. After completing 5 meal interventions (3-9 weeks)
Comparison of mean glucose levels between AP with empagliflozin with simple meal announcement strategy and AP without empagliflozin with carb-counting. After completing 5 meal interventions (3-9 weeks)
Secondary Outcome
Measure Time Frame
Time spent in hypoglycemia After completing 5 meal interventions (3-9 weeks)
Number of hypoglycemic events below 3.3 mmol/L After completing 5 meal interventions (3-9 weeks)
Number of clinically remarkable hypoglycemic events After completing 5 meal interventions (3-9 weeks)
Number of treated hypoglycemic events After completing 5 meal interventions (3-9 weeks)
Mean continuous glucose monitoring (CGM) glucose level After completing 5 meal interventions (3-9 weeks)
Standard deviation of glucose levels After completing 5 meal interventions (3-9 weeks)
Coefficient of variation of glucose levels After completing 5 meal interventions (3-9 weeks)
Total insulin delivery After completing 5 meal interventions (3-9 weeks)
Morning capillary ketone concentration After completing 5 meal interventions (3-9 weeks)
Enrollment 36
Condition
Intervention

Intervention Type: Drug

Intervention Name: Empagliflozin 25mg

Description: Individuals will test insulin dosing during different meal strategies (carbohydrate counting, plain meal announcement, no meal announcement) in a setting of the single hormone artificial pancreas with or without SGLT2 inhibitor (empagliflozin) addition. After starting the empagliflozin therapy, there will be 1-2 weeks long therapy optimization period and afterwards meal strategies will be administered. Randomization will be used to determine whether participant will start meal strategies on empagliflozin or without empagliflozin, cross-over design enables all participants to undergo all combination of approaches.

Arm Group Label: Main arm

Intervention Type: Device

Intervention Name: Single hormone artificial pancreas

Description: Single hormone artificial pancreas will be used as a baseline background intervention standardizing the delivery and dosing of insulin. Artificial pancreas (insulin pump, continuous glucose monitoring device and dosing-suggestion algorithm) will be used by all participants on days when meal strategy intervention will be performed.

Arm Group Label: Main arm

Intervention Type: Behavioral

Intervention Name: Meal strategies

Description: Participants will use different approaches (strategies) to insulin dose estimation for ingested carbohydrates on study days. Goal of these various strategies is to recognize magnitude of empagliflozin effect in situations when artificial pancreas algorithm is working with information of different accuracy. Individual meal approach strategies include carbohydrate counting, meal size announcement and no meal announcement. The exception will be combination of no empagliflozin and no meal announcement, which didn't result in sufficient glucose control in previous trials therefore will not be repeated in a current trial. Meal approach strategies will occur on separate days- 5 days in total each day using one meal strategy for all meals during the day.

Arm Group Label: Main arm

Eligibility

Criteria:

Inclusion Criteria:

1. Clinical diagnosis of type 1 diabetes for at least one year.

2. Use of insulin pump therapy for at least 3 months.

3. HbA1c ≤ 10%.

4. Women of childbearing potential must agree to use adequate birth control during participation in the study

Exclusion Criteria:

1. Clinically significant nephropathy, neuropathy or retinopathy.

2. Recent acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.

3. History of pheochromocytoma or insulinoma

4. Use of loop diuretics, anticholinergic drugs, beta-blockers at high dose, glucocorticoids (except low stable dose and inhaled steroids), chronic acetaminophen treatment, chronic warfarin treatment

5. Use of non-insulin adjunct anti-hyperglycaemic drug (e.g. metformin, glucagon-like peptide analogues, etc.).

6. Ongoing or planned pregnancy or breastfeeding.

7. Recent severe hypoglycemic episode prior to enrollment

8. Recent diabetic ketoacidosis prior to enrollment

9. Recent history of genital or urinary infection prior to enrollment

10. History of lower limb amputation and recent history of leg or foot infection or wound

11. Anticipating a significant change in exercise regimen between initiations of two intervention blocks (i.e. starting or stopping an organized sport).

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Bruce A. Perkins, MD Principal Investigator Samuel Lunenfeld Research Institute, TGRI
Overall Contact

Last Name: Bruce A. Perkins, MD

Phone: (416) 586-8763

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
Sinai Health System | Toronto, Ontario, M5T 3L9, Canada Recruiting Andrej Orszag 416-586-4800 [email protected] Bruce A. Perkins, MD Principal Investigator
Institut de recherches cliniques de Montréal | Montréal, Quebec, H2W 1R7, Canada Recruiting Virginie Messier, B.Sc. 514 987-5500 [email protected] Rémi Rabasa-Lhoret, MD, PhD Principal Investigator
McGill University Health Center | Montréal, Quebec, H3A 2B4, Canada Recruiting 514-398-4491 [email protected] Ahmad Haidar Principal Investigator
Location Countries

Canada

Verification Date

November 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Main arm

Type: Experimental

Description: Single arm open-label cross-over study with random order of SGLT-2 inhibitor intervention (Empagliflozin 25mg po qd), in which each cross-over phase includes different meal strategies (carbohydrate counting, meal announcement, no meal announcement) on separate days in the setting of single hormone artificial pancreas

Acronym CLASS15
Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov