- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03510000
Alleviating Carbohydrate-Counting Burden in T1DM Using Artificial Pancreas and Empagliflozin (CLASS15)
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5T 3L9
- Sinai Health System
-
-
Quebec
-
Montréal, Quebec, Canada, H2W 1R7
- Institut de Recherches Cliniques de Montreal
-
Montréal, Quebec, Canada, H3A 2B4
- McGill University Health Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Main arm
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
|
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.
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
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.
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
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.
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time spent in hypoglycemia
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
Percentage of time spent in the following glucose sensor levels:
|
After completing 5 meal interventions (3-9 weeks)
|
Number of hypoglycemic events below 3.3 mmol/L
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
Number of hypoglycemic events (> 20 minutes) below 3.3 mmol/L based on continuous glucose monitoring sensor glucose level values.
|
After completing 5 meal interventions (3-9 weeks)
|
Number of clinically remarkable hypoglycemic events
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
Number of symptomatic hypoglycemic events below 4.0 mmol/l or below 3.5 mmol/l without symptoms.
|
After completing 5 meal interventions (3-9 weeks)
|
Number of treated hypoglycemic events
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
Number of hypoglycemic events or events perceived as hypoglycemia which prompt treatment by glucose or glucagon or overriding AP insulin dosing algorithm suggestion or by administering the regular meal earlier than planned.
|
After completing 5 meal interventions (3-9 weeks)
|
Mean continuous glucose monitoring (CGM) glucose level
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
Comparison of mean CGM glucose levels between different meal interventions on and off empagliflozin.
|
After completing 5 meal interventions (3-9 weeks)
|
Standard deviation of glucose levels
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
Comparison of values obtained from CGM on different meal intervention days.
|
After completing 5 meal interventions (3-9 weeks)
|
Coefficient of variation of glucose levels
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
Comparison of values obtained from CGM on different meal intervention days.
|
After completing 5 meal interventions (3-9 weeks)
|
Total insulin delivery
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
Comparison of total insulin delivered by AP on different meal intervention days.
|
After completing 5 meal interventions (3-9 weeks)
|
Morning capillary ketone concentration
Time Frame: After completing 5 meal interventions (3-9 weeks)
|
Safety outcome to assess risk of Empagliflozin related most serious side effect-diabetic ketoacidosis.
Evaluated will be all days of study participation (i.e.not
only meal intervention days)
|
After completing 5 meal interventions (3-9 weeks)
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Bruce A. Perkins, MD, Samuel Lunenfeld Research Institute, TGRI
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Gastrointestinal Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Sodium-Glucose Transporter 2 Inhibitors
- Hormones
- Empagliflozin
- Pancrelipase
Other Study ID Numbers
- CLASS15
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type1diabetes
-
Silesian Centre for Heart DiseasesThe Jerzy Kukuczka Academy of Physical Education in KatowiceCompletedtype1diabetesPoland
-
Vastra Gotaland RegionCompletedType1diabetesSweden
-
Rabin Medical CenterThe Leona M. and Harry B. Helmsley Charitable Trust; DreaMed DiabetesRecruiting
-
University of Southern CaliforniaThe Leona M. and Harry B. Helmsley Charitable TrustCompletedType1diabetesUnited States
-
The Hospital for Sick ChildrenCanadian Institutes of Health Research (CIHR)Active, not recruiting
-
Aalborg University HospitalAalborg University; Steno Diabetes Center NordjyllandCompletedType1diabetes | Hemodialysis | Type2DiabetesDenmark
-
Vastra Gotaland RegionRecruitingType1diabetes | Psychology Functional BehaviorSweden
-
Radboud University Medical CenterUnknownType1diabetes | Hypoglycemia UnawarenessNetherlands
-
University of PennsylvaniaNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National...Active, not recruitingHypoglycemia | Type1diabetes | Islet Cell Transplantation | Hypoglycemia UnawarenessUnited States
-
University of British ColumbiaJuvenile Diabetes Research Foundation; Brain CanadaNot yet recruiting
Clinical Trials on Empagliflozin 25mg
-
Chong Kun Dang PharmaceuticalUnknownDiabetes Mellitus, Type IIKorea, Republic of
-
University Medical Centre LjubljanaUnknownDiabetes Complications | Diabetes Mellitus, Type 1 | Vascular Stiffness | Hypoglycemic AgentsSlovenia
-
University Hospital, Basel, SwitzerlandCompletedHyponatremia | SIAD - Syndrome of Inappropriate AntidiuresisSwitzerland
-
University Hospital TuebingenCompletedBody Weight | PreDiabetesGermany
-
National Taiwan University HospitalShin Kong Wu Ho-Su Memorial HospitalNot yet recruitingHeart Failure With Reduced Ejection Fraction | End Stage Renal Disease on Dialysis
-
Boehringer IngelheimCompletedDiabetes Mellitus, Type 2Korea, Republic of
-
University Hospital, Basel, SwitzerlandCompletedInappropriate ADH SyndromeSwitzerland
-
University of DundeeBritish Heart FoundationCompletedHeart Failure | Type 2 Diabetes MellitusUnited Kingdom
-
Boehringer IngelheimEli Lilly and CompanyCompletedDiabetes Mellitus, Type 1Austria, Germany