Diabetes Mellitus, Type 1Phase 3NCT04049110
Dapagliflozin in Physical Exercise in Type 1 Diabetes
A Phase 3 study testing Forxiga 10mg in people with Diabetes Mellitus, Type 1, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
Inhibitors of sodium-dependent glucose-transporter 2 (SGLT-2 inhibitors, including dapagliflozin) inhibit glucose reabsorption in renal tubular cells, hereby increasing glycosuria in the hyperglycemic state. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Forxiga 10mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteSwitzerland
- Study dates
- 25 Aug 2020to 10 May 2023
- Phase
- Phase 3
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Diagnosis of T1DM
- Duration of T1DM > 5 years
- Male or female sex
- Insulin therapy via multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII)
- Body mass index (BMI) between 20 and 29 kg/m2
- Adherence to sufficient contraceptive measures (double barrier method combining hormonal with mechanical barriers).
- Ability to perform a 60 minutes exercise session at 50% VO2max.
Who cannot join
- Diagnosis of renal and/or hepatic dysfunction
- History of malignancy of any kind
- Intake of drugs influencing glucose homeostasis during the last three months
- Alcohol or drug abuse
- Inadequate vein status on both forearms
- Active smoker
- Known pregnancy, positive plasma beta human choriogonadotropine test prior to study inclusion or intention to become pregnant during the study period.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Bern, 3010
About this study
Official title: SGLT-2 Inhibition Using Dapagliflozin During and After Physical Exercise - Effects on Glycemic Variability, Hormonal Regulators of Glucose Homeostasis and Ketone Body in Type 1 Diabetes - a Randomized, Placebo-controlled, Open-label, Cross-over Intervention Study
Inhibitors of sodium-dependent glucose-transporter 2 (SGLT-2 inhibitors, including dapagliflozin) inhibit glucose reabsorption in renal tubular cells, hereby increasing glycosuria in the hyperglycemic state. Its mechanisms of action are independent of insulin, which makes SGLT-2 inhibitors a potential adjunct to insulin in type 1 diabetes mellitus (T1DM).
However, a higher risk for diabetic ketoacidosis (DKA) was reported in patients with T1DM taking SGLT-2 inhibitors. DKA depends on an accumulation of ketone bodies in the blood stream, which equals an accumulation of acids that lead to acidosis. The underlying mechanisms of this observation are unknown. Ketone body production depends on the molar ratio of glucagon to insulin, with insulin suppressing but glucagon stimulating ketone body production. This translates into higher production during relative insulin deficiency, carbohydrate deficiency, and prolonged fasting, which occurs during sickness but also physical exercise. Physical exercise is a recommended cornerstone in the treatment of T1DM and current treatment guidelines recommend both, reductions of insulin doses and ingestion of additional carbohydrates to avoid hypoglycemic events. These adaptions might increase relative insulin deficiency, hyperglycemia and glycaemic variability, which might in turn promote ketone body production. The addition of SGLT-2 inhibitors further may promote ketogenesis even though there are reports of SGLT-2 inhibitors increase Glucagon-like-peptide-1 (GLP-1) in patients with T1DM. GLP-1 is a suppressor of glucagon secretion. In summary, knowledge about the effects of SGLT-2 inhibition on ketone body production is scarce, especially during exercise in patients with T1DM.
The study seeks to illustrate the effect of SGLT-2 inhibition on glycemic variability and ketone body production during and after recreational exercise in patients with T1DM. The results of study 2 will provide the basis for future studies investigating the underlying mechanisms of potentially modified ketone body production during and after exercise under SGLT-2 inhibition.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Forxiga 10mg, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Forxiga 10mgDrug
Also called Dapagliflozin
Dapagliflozin 10mg per 24 hours, oral, for 7 consecutive days
PlaceboDrug
Placebo 1 tablet per 24 hours, oral, for 7 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin first, placebo second | Experimental | Dapagliflozin followed by placebo Receives: Drug: Forxiga 10mg; Drug: Placebo |
| Placebo first, Dapagliflozin second | Experimental | Placebo followed by dapagliflozin Receives: Drug: Forxiga 10mg; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Amplitude of Glucose Excursions (MAGE) after physical exercise
MAGE will be calculated via sensor glucose measurements obtained over 72 hours after physical exercise
Measured: From completion of physical exercise at day 7 of each intervention period to 72 hours after
Secondary outcomes (2)
Area under the curve for glucagon-like peptide I before, during and after physical exercise
Glucagon-like peptide I will be measured at the beginning, during and after physical exercise following each intervention period
Measured: From time-point 0 to 120 minutes before, during and after physical exercise session
Area under the curve for glucagon before, during and after physical exercise
Glucagon will be measured at the beginning, during and after physical exercise following each intervention period
Measured: From time-point 0 to 120 minutes before, during and after physical exercise session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2019
- Study start25 Aug 2020
- Primary completion26 Apr 2023
- Study completion10 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, placebo-controlled, open-label, crossover
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christoph Stettler, Prof. MD, Principal investigator, Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, University Clinics Bern, Inselspital, Bern, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04049110
- Sponsor's protocol ID
- CUI_002_02
- Status last verified
- Aug 2023
- First submitted
- 5 Aug 2019
- Last updated
- 31 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SGLT-2 Inhibition Using Dapagliflozin During and After Physical Exercise - Effects on Glycemic Variability, Hormonal Regulators of Glucose Homeostasis and Ketone Body in Type 1 Diabetes - a Randomized, Placebo-controlled, Open-label, Cross-over Intervention Study
- ClinicalTrials.gov ID
- NCT04049110
- Acronym / sponsor ID
- CUI_002_02
- Conditions
- Diabetes Mellitus, Type 1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 25 Aug 2020 (actual)
- Primary completion
- 26 Apr 2023 (actual)
- Study completion
- 10 May 2023 (actual)
- First posted
- 7 Aug 2019 (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.
Inhibitors of sodium-dependent glucose-transporter 2 (SGLT-2 inhibitors, including dapagliflozin) inhibit glucose reabsorption in renal tubular cells, hereby increasing glycosuria in the hyperglycemic state. Its mechanisms of action are independent of insulin, which makes SGLT-2 inhibitors a potential adjunct to insulin in type 1 diabetes mellitus (T1DM).
However, a higher risk for diabetic ketoacidosis (DKA) was reported in patients with T1DM taking SGLT-2 inhibitors. DKA depends on an accumulation of ketone bodies in the blood stream, which equals an accumulation of acids that lead to acidosis. The underlying mechanisms of this observation are unknown. Ketone body production depends on the molar ratio of glucagon to insulin, with insulin suppressing but glucagon stimulating ketone body production. This translates into higher production during relative insulin deficiency, carbohydrate deficiency, and prolonged fasting, which occurs during sickness but also physical exercise. Physical exercise is a recommended cornerstone in the treatment of T1DM and current treatment guidelines recommend both, reductions of insulin doses and ingestion of additional carbohydrates to avoid hypoglycemic events. These adaptions might increase relative insulin deficiency, hyperglycemia and glycaemic variability, which might in turn promote ketone body production. The addition of SGLT-2 inhibitors further may promote ketogenesis even though there are reports of SGLT-2 inhibitors increase Glucagon-like-peptide-1 (GLP-1) in patients with T1DM. GLP-1 is a suppressor of glucagon secretion. In summary, knowledge about the effects of SGLT-2 inhibition on ketone body production is scarce, especially during exercise in patients with T1DM.
The study seeks to illustrate the effect of SGLT-2 inhibition on glycemic variability and ketone body production during and after recreational exercise in patients with T1DM. The results of study 2 will provide the basis for future studies investigating the underlying mechanisms of potentially modified ketone body production during and after exercise under SGLT-2 inhibition.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, placebo-controlled, open-label, crossover
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin first, placebo second | Experimental | Drug: Forxiga 10mg, Drug: PlaceboDapagliflozin followed by placebo |
| Placebo first, Dapagliflozin second | Experimental | Drug: Forxiga 10mg, Drug: PlaceboPlacebo followed by dapagliflozin |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent
- Diagnosis of T1DM
- Duration of T1DM > 5 years
- Male or female sex
- Insulin therapy via multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII)
Key exclusion criteria (7 listed)
- Diagnosis of renal and/or hepatic dysfunction
- History of malignancy of any kind
- Intake of drugs influencing glucose homeostasis during the last three months
- Alcohol or drug abuse
- Inadequate vein status on both forearms
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 |
|---|---|---|
| Forxiga 10mgAlso: DapagliflozinDapagliflozin 10mg per 24 hours, oral, for 7 consecutive days | Drug | Dapagliflozin first, placebo second, Placebo first, Dapagliflozin second |
| PlaceboPlacebo 1 tablet per 24 hours, oral, for 7 consecutive days | Drug | Dapagliflozin first, placebo second, Placebo first, Dapagliflozin second |
Primary outcome
Mean Amplitude of Glucose Excursions (MAGE) after physical exercise
Time frame: From completion of physical exercise at day 7 of each intervention period to 72 hours after
MAGE will be calculated via sensor glucose measurements obtained over 72 hours after physical exercise
2 secondary outcomes
Area under the curve for glucagon-like peptide I before, during and after physical exercise
Time frame: From time-point 0 to 120 minutes before, during and after physical exercise session
Area under the curve for glucagon before, during and after physical exercise
Time frame: From time-point 0 to 120 minutes before, during and after physical exercise session
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 31 Aug 2023.
- Individual participant dataSharing planned: Yes
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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.
Christoph Stettler, Prof. MD principal investigator
Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, University Clinics Bern, Inselspital, Bern, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Forxiga 10mg in people with Diabetes Mellitus, Type 1, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 8 inclusion and 7 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 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Mean Amplitude of Glucose Excursions (MAGE) after physical exercise (time frame: From completion of physical exercise at day 7 of each intervention period to 72 hours after). 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 31 Aug 2023.