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

NCT03510000 | Completed

• 1 other identifier: CLASS15
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

Type1diabetes

Keywords

T1DM; artificial pancreas; insulin pump; empagliflozin; SGLT2 inhibitor; carbohydrate counting

Outcome Measures

Primary Outcomes (2)

• 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.

  Non-inferiority comparison of mean 14-hour glucose level obtained by continuous glucose monitoring between i) the AP with empagliflozin with no meal-announcement and ii) the AP with quantitative carbohydrate-counting without empagliflozin.

  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.

  If there is a significant difference in the previous non-inferiority comparison, the following conditional primary comparison will be conducted: Non-inferiority comparison of mean 14-hour sensor glucose level obtained by continuous glucose monitoring between i) the AP with empagliflozin with simple meal-announcement and ii) the AP with quantitative carbohydrate-counting without empagliflozin.

  After completing 5 meal interventions (3-9 weeks)

Secondary Outcomes (9)

• 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)

Study Arms (1)

Main arm

EXPERIMENTAL

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

Drug: Empagliflozin 25mg; Device: Single hormone artificial pancreas; Behavioral: Meal strategies

Interventions

Empagliflozin 25mg DRUG

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.

Main arm

Single hormone artificial pancreas DEVICE

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.

Main arm

Meal strategies BEHAVIORAL

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.

Main arm

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of type 1 diabetes for at least one year.
• Use of insulin pump therapy for at least 3 months.
• HbA1c ≤ 10%.
• Women of childbearing potential must agree to use adequate birth control during participation in the study

You may not qualify if:

• Clinically significant nephropathy, neuropathy or retinopathy.
• Recent acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• History of pheochromocytoma or insulinoma
• 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
• Use of non-insulin adjunct anti-hyperglycaemic drug (e.g. metformin, glucagon-like peptide analogues, etc.).
• Ongoing or planned pregnancy or breastfeeding.
• Recent severe hypoglycemic episode prior to enrollment
• Recent diabetic ketoacidosis prior to enrollment
• Recent history of genital or urinary infection prior to enrollment
• History of lower limb amputation and recent history of leg or foot infection or wound
• Anticipating a significant change in exercise regimen between initiations of two intervention blocks (i.e. starting or stopping an organized sport).

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead
• Canadian Diabetes Association: collaborator
• Institut de Recherches Cliniques de Montreal: collaborator
• McGill University Health Centre/Research Institute of the McGill University Health Centre: collaborator

Study Sites (3)

Sinai Health System

Toronto, Ontario, M5T 3L9, Canada

Location

Institut de recherches cliniques de Montréal

Montreal, Quebec, H2W 1R7, Canada

Location

McGill University Health Center

Montreal, Quebec, H3A 2B4, Canada

Location

MeSH Terms

Interventions

empagliflozin

Study Officials

• Bruce A. Perkins, MD

  Samuel Lunenfeld Research Institute, TGRI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2018
• First Posted: April 27, 2018
• Study Start: May 15, 2018
• Primary Completion: November 21, 2019
• Study Completion: November 21, 2019
• Last Updated: June 24, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)