Type1diabetesCLASS15NCT03510000
Alleviating Carbohydrate-Counting Burden in T1DM Using Artificial Pancreas and Empagliflozin
A study testing Empagliflozin 25mg, Single hormone artificial pancreas and Meal strategies in people with Type1diabetes, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 3 sites in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type1diabetes
- What is being tested?
- Empagliflozin 25mg, Single hormone artificial pancreas and Meal strategies
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesCanada
- Study dates
- 15 May 2018to 21 Nov 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 11Show fewer
- 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).
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Institut de recherches cliniques de Montréal
Montreal, Quebec, H2W 1R7
McGill University Health Center
Montreal, Quebec, H3A 2B4
Sinai Health System
Toronto, Ontario, M5T 3L9
About this study
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.
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.
Read the 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.
- Conditions
- Type1diabetes
- Being tested
- Empagliflozin 25mg, Single hormone artificial pancreas, Meal strategies
- Keywords
- T1DM, artificial pancreas, insulin pump, empagliflozin, SGLT2 inhibitor, carbohydrate counting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 25mgDrug
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 pancreasDevice
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.
Meal strategiesBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Empagliflozin 25mg; Device: Single hormone artificial pancreas; Behavioral: Meal strategies |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: After completing 5 meal interventions (3-9 weeks)
Secondary outcomes (9)
Time spent in hypoglycemia
Percentage of time spent in the following glucose sensor levels:
- Between 3.9 and 10.0 mmol/l
- Between 3.9 and 7.8 mmol/l
- Above 7.8 mmol/l
- Above 10.0 mmol/l
- Above 13.9 mmol/l
- Below 3.9 mmol/l
- Below 3.3 mmol/l
- Below 2.8 mmol/l.
Measured: After completing 5 meal interventions (3-9 weeks)
Number of hypoglycemic events below 3.3 mmol/L
Number of hypoglycemic events (> 20 minutes) below 3.3 mmol/L based on continuous glucose monitoring sensor glucose level values.
Measured: After completing 5 meal interventions (3-9 weeks)
Number of clinically remarkable hypoglycemic events
Number of symptomatic hypoglycemic events below 4.0 mmol/l or below 3.5 mmol/l without symptoms.
Measured: After completing 5 meal interventions (3-9 weeks)
Number of treated hypoglycemic events
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.
Measured: After completing 5 meal interventions (3-9 weeks)
Mean continuous glucose monitoring (CGM) glucose level
Comparison of mean CGM glucose levels between different meal interventions on and off empagliflozin.
Measured: After completing 5 meal interventions (3-9 weeks)
Standard deviation of glucose levels
Comparison of values obtained from CGM on different meal intervention days.
Measured: After completing 5 meal interventions (3-9 weeks)
Coefficient of variation of glucose levels
Comparison of values obtained from CGM on different meal intervention days.
Measured: After completing 5 meal interventions (3-9 weeks)
Total insulin delivery
Comparison of total insulin delivered by AP on different meal intervention days.
Measured: After completing 5 meal interventions (3-9 weeks)
Morning capillary ketone concentration
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)
Measured: After completing 5 meal interventions (3-9 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2018
- Study start15 May 2018
- Primary completion21 Nov 2019
- Study completion21 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type1diabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Diabetes Association, Institut de Recherches Cliniques de Montreal, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Responsible party
- Sponsor
- Investigators
- Bruce A. Perkins, MD, Principal investigator, Samuel Lunenfeld Research Institute, TGRI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03510000
- Sponsor's protocol ID
- CLASS15
- Acronym
- CLASS15
- Status last verified
- Jun 2021
- First submitted
- 24 Jan 2018
- Last updated
- 24 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03510000
- Acronym / sponsor ID
- CLASS15 / CLASS15
- Conditions
- Type1diabetes
- Keywords
- T1DM, artificial pancreas, insulin pump, empagliflozin, SGLT2 inhibitor, carbohydrate counting
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Collaborators
- Canadian Diabetes Association, Institut de Recherches Cliniques de Montreal, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Study start
- 15 May 2018 (actual)
- Primary completion
- 21 Nov 2019 (actual)
- Study completion
- 21 Nov 2019 (actual)
- First posted
- 27 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Main arm | Experimental | Drug: Empagliflozin 25mg, Device: Single hormone artificial pancreas, Behavioral: Meal strategiesSingle 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 25mgIndividuals 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. | Drug | Main arm |
| Single hormone artificial pancreasSingle 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. | Device | Main arm |
| Meal strategiesParticipants 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. | Behavioural | Main arm |
Primary outcome
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.
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.
9 secondary outcomes
Time spent in hypoglycemia
Time frame: 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 clinically remarkable hypoglycemic events
Time frame: After completing 5 meal interventions (3-9 weeks)
Number of treated hypoglycemic events
Time frame: 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)
Standard deviation of glucose levels
Time frame: After completing 5 meal interventions (3-9 weeks)
Coefficient of variation of glucose levels
Time frame: After completing 5 meal interventions (3-9 weeks)
Total insulin delivery
Time frame: After completing 5 meal interventions (3-9 weeks)
Morning capillary ketone concentration
Time frame: After completing 5 meal interventions (3-9 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce A. Perkins, MD principal investigator
Samuel Lunenfeld Research Institute, TGRI
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Empagliflozin 25mg, Single hormone artificial pancreas and Meal strategies in people with Type1diabetes, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 3 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: After completing 5 meal interventions (3-9 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2021.