Clinical trial NCT03510000: Alleviating Carbohydrate-Counting Burden in T1DM Using Artificial Pancreas and Empagliflozin
Official title: Alleviating Carbohydrate-Counting Burden in Type 1 Diabetes Using Artificial Pancreas and Sodium Glucose-Linked Transporter 2 Inhibition: A Randomized Open-Label Crossover Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type1diabetes
Keywords: T1DM
artificial pancreas
insulin pump
empagliflozin
SGLT2 inhibitor
carbohydrate counting
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
Collaborators: name: Canadian Diabetes Association
name: Institut de Recherches Cliniques de Montreal
name: McGill University Health Centre/Research Institute of the McGill University Health Centre
First posted: 2018-04-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: 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.
timeFrame: After completing 5 meal interventions (3-9 weeks)
measure: Comparison of mean glucose levels between AP with empagliflozin with simple meal announcement strategy and AP without empagliflozin with carb-counting.
timeFrame: After completing 5 meal interventions (3-9 weeks)
Secondary outcomes:
measure: Time spent in hypoglycemia
timeFrame: After completing 5 meal interventions (3-9 weeks)
measure: Number of hypoglycemic events below 3.3 mmol/L
timeFrame: After completing 5 meal interventions (3-9 weeks)
measure: Number of clinically remarkable hypoglycemic events
timeFrame: After completing 5 meal interventions (3-9 weeks)
measure: Number of treated hypoglycemic events
timeFrame: After completing 5 meal interventions (3-9 weeks)
measure: Mean continuous glucose monitoring (CGM) glucose level
timeFrame: After completing 5 meal interventions (3-9 weeks)
measure: Standard deviation of glucose levels
timeFrame: After completing 5 meal interventions (3-9 weeks)
measure: Coefficient of variation of glucose levels
timeFrame: After completing 5 meal interventions (3-9 weeks)
measure: Total insulin delivery
timeFrame: After completing 5 meal interventions (3-9 weeks)
measure: Morning capillary ketone concentration
timeFrame: After completing 5 meal interventions (3-9 weeks)
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sinai Health System
state: Ontario
city: Montréal
country: Canada
facility: Institut de recherches cliniques de Montréal
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Center
state: Quebec
Study officials:
affiliation: Samuel Lunenfeld Research Institute, TGRI
name: Bruce A. Perkins, MD
role: PRINCIPAL_INVESTIGATOR
References: