Diabetes Mellitus, Type 1Phase 2NCT03556033
Effect of Dapagliflozin on IAH in T1DM
A Phase 2 study testing Dapagliflozin in people with Diabetes Mellitus, Type 1 and Hypoglycemia, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Approximately 25% of patients with type 1 diabetes have lost the capacity to timely detect hypoglycaemia, a condition referred to as impaired awareness of hypoglycaemia (IAH) that causes a six-fold higher risk of severe, potentially hazardous, hypoglycaemia. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 1, Hypoglycemia, Hypoglycemia Unawareness
- What is being tested?
- Dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteNetherlands
- Study dates
- 23 Nov 2018to 20 Dec 2019
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes, disease duration >1 year
- Age >18 years, <75 years
- BMI 19-40 kg/m^2
- Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump)
- Impaired awareness of hypoglycemia as assessed by a score of 3 or more on the modified Dutch translation of the Clarke questionnaire
- Glycated haemoglobin (HbA1c) ≥42 mmol/mol (6%) and ≤75 mmol/mol (9.0%)
- Ability to provide informed consent
Who cannot join
- Treatment with SGLT-2 inhibitors
- Known intolerance to SGLT-2 inhibitors
- Treatment with loop diuretics or other anti-hypertensive agents
- Treatment with glucose-modifying (other than insulin) or immune-modifying agents (e.g. prednisolon)
- Treatment with pioglitazone
- Use of statins
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- A history of cardiovascular disease (e.g. myocardial infarction, stroke, heart failure) or hypotension
- A history of galactose-intolerance, lactase deficiency, glucose-galactose malabsorption
- History of diabetic ketoacidosis requiring medical intervention within 1 month before screening
- Admission to the hospital for hyperglycemia or hypoglycemia within 1 month before screening
- Frequent episodes of severe hypoglycemia within 1 month before screening
- Laser coagulation for proliferative retinopathy (past 6 months)
- Proliferative retinopathy
- Diabetic nephropathy as reflected by an albumin-creatinin ratio ˃ 30 mmol/mg or an estimated glomerular filtration rate (by MDRD) ˂60ml/min/1.73m2
- History of pancreatitis (acute or chronic) or pancreatic cancer
- Use of premixed insulin or of long-acting insulin alone
- Total daily insulin dose requirements <20 units unless on pump treatment
- Pregnancy or unwillingness to undertake measures for birth control
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of the SGLT-2 Inhibitor Dapagliflozin on Impaired Awareness of Hypoglycemia in Type 1 Diabetes
Approximately 25% of patients with type 1 diabetes have lost the capacity to timely detect hypoglycaemia, a condition referred to as impaired awareness of hypoglycaemia (IAH) that causes a six-fold higher risk of severe, potentially hazardous, hypoglycaemia. IAH is usually the end-result of a process of habituation to recurrent hypoglycaemia that is potentially reversible. Treatment with sodium glucose cotransporter (SGLT)-2 inhibitors (SGLT-2i) in addition to insulin therapy may decrease the incidence of hypoglycaemia in patients with type 1 diabetes. This study will test the hypothesis that treatment with the SGLT-2 inhibitor, dapagliflozin, added to basal-bolus insulin therapy will improve awareness of hypoglycaemia in patients with type 1 diabetes and IAH. In a randomized doubleblind placebo-controlled cross-over trial, patients will be treated for 8 weeks with dapagliflozin (or placebo), after which hypoglycemic symptoms and counterregulatory hormone responses will be examined during a hyperinsulinemic hypoglycemic glucose clamp study.
- Being tested
- Dapagliflozin, Placebo oral capsule
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
Also called Forxiga
8 weeks treatment with dapagliflozin on top of insulin treatment
Placebo oral capsuleDrug
8 weeks treatment with placebo capsules on top of insulin treatment
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin | Active comparator | Dapagliflozin 10 mg capsule once daily for 8 weeks Receives: Drug: Dapagliflozin |
| Placebo oral capsule | Placebo comparator | Placebo matched to dapagliflozin 10 mg capsule once daily for 8 weeks Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptom score in response to insulin-induced hypoglycaemia
Symptom scores (autonomic, neuroglycopenic and general) measured during hyperinsulinemic hypoglycaemic glucose clamps. This questionnaire consists of 18 symptoms, which can be scored between 0 (none) to 6 (severe). Total scores range between 0 and 108, the higher the score, the more symptoms patients have during and after hypoglycemia.
Measured: 45 minutes
Secondary outcomes (10)
Counterregulatory hormone responses to insulin-induced hypoglycaemia
(nor)adrenaline, glucagon, insulin, growth hormone and cortisol responses to hypoglycaemia measured during hyperinsulinemic hypoglycaemic glucose clamps
Measured: 45 minutes
Time until glycaemic recovery from hypoglycaemia
measured during hyperinsulinemic hypoglycaemic glucose clamps
Measured: 45 minutes
Maximal glucose excursion post-hypoglycaemia
Maximal glucose level (mmol/l) measured during the 90 minutes after ending the hypoglycaemic phase of the clamp (during restoration of euglycaemia)
Measured: 45 minutes
Time until glucose peak post-hypoglycaemia
measured during hyperinsulinemic hypoglycaemic glucose clamps
Measured: 45 minutes
Area under the glucose concentration curve post-hypoglycaemia
measured during hyperinsulinemic hypoglycaemic glucose clamps
Measured: 45 minutes
Number of severe hypoglycaemic events during follow-up
measured during follow-up
Measured: 16 weeks
Number of nocturnal hypoglycaemic events during follow-up
measured during follow-up
Measured: 16 weeks
Number of any hypoglycaemic events during follow-up
measured during follow-up
Measured: 16 weeks
Time spent under hypoglycaemic conditions measured by glucose sensor monitoring
measured during follow-up
Measured: 2 weeks
Glucose variability as measured by glucose sensor monitoring
measured during follow-up
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2018
- Study start23 Nov 2018
- Primary completion20 Dec 2019
- Study completion20 Dec 2019
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 Radboud University Medical CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03556033
- Sponsor's protocol ID
- T1DM_IAH_dapa
- Status last verified
- Sep 2019
- First submitted
- 17 May 2018
- Last updated
- 23 Mar 2020
- 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 23 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of the SGLT-2 Inhibitor Dapagliflozin on Impaired Awareness of Hypoglycemia in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03556033
- Acronym / sponsor ID
- T1DM_IAH_dapa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 23 Nov 2018 (actual)
- Primary completion
- 20 Dec 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 14 Jun 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.
Approximately 25% of patients with type 1 diabetes have lost the capacity to timely detect hypoglycaemia, a condition referred to as impaired awareness of hypoglycaemia (IAH) that causes a six-fold higher risk of severe, potentially hazardous, hypoglycaemia. IAH is usually the end-result of a process of habituation to recurrent hypoglycaemia that is potentially reversible. Treatment with sodium glucose cotransporter (SGLT)-2 inhibitors (SGLT-2i) in addition to insulin therapy may decrease the incidence of hypoglycaemia in patients with type 1 diabetes. This study will test the hypothesis that treatment with the SGLT-2 inhibitor, dapagliflozin, added to basal-bolus insulin therapy will improve awareness of hypoglycaemia in patients with type 1 diabetes and IAH. In a randomized doubleblind placebo-controlled cross-over trial, patients will be treated for 8 weeks with dapagliflozin (or placebo), after which hypoglycemic symptoms and counterregulatory hormone responses will be examined during a hyperinsulinemic hypoglycemic glucose clamp study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Active comparator | Drug: DapagliflozinDapagliflozin 10 mg capsule once daily for 8 weeks |
| Placebo oral capsule | Placebo comparator | Drug: Placebo oral capsulePlacebo matched to dapagliflozin 10 mg capsule once daily for 8 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Type 1 diabetes, disease duration >1 year
- Age >18 years, <75 years
- BMI 19-40 kg/m^2
- Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump)
- Impaired awareness of hypoglycemia as assessed by a score of 3 or more on the modified Dutch translation of the Clarke questionnaire
Key exclusion criteria (18 listed)
- Treatment with SGLT-2 inhibitors
- Known intolerance to SGLT-2 inhibitors
- Treatment with loop diuretics or other anti-hypertensive agents
- Treatment with glucose-modifying (other than insulin) or immune-modifying agents (e.g. prednisolon)
- Treatment with pioglitazone
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 |
|---|---|---|
| DapagliflozinAlso: Forxiga8 weeks treatment with dapagliflozin on top of insulin treatment | Drug | Dapagliflozin |
| Placebo oral capsule8 weeks treatment with placebo capsules on top of insulin treatment | Drug | Placebo oral capsule |
Primary outcome
Symptom score in response to insulin-induced hypoglycaemia
Time frame: 45 minutes
Symptom scores (autonomic, neuroglycopenic and general) measured during hyperinsulinemic hypoglycaemic glucose clamps. This questionnaire consists of 18 symptoms, which can be scored between 0 (none) to 6 (severe). Total scores range between 0 and 108, the higher the score, the more symptoms patients have during and after hypoglycemia.
10 secondary outcomes
Counterregulatory hormone responses to insulin-induced hypoglycaemia
Time frame: 45 minutes
Time until glycaemic recovery from hypoglycaemia
Time frame: 45 minutes
Maximal glucose excursion post-hypoglycaemia
Time frame: 45 minutes
Time until glucose peak post-hypoglycaemia
Time frame: 45 minutes
Area under the glucose concentration curve post-hypoglycaemia
Time frame: 45 minutes
Number of severe hypoglycaemic events during follow-up
Time frame: 16 weeks
Number of nocturnal hypoglycaemic events during follow-up
Time frame: 16 weeks
Number of any hypoglycaemic events during follow-up
Time frame: 16 weeks
Time spent under hypoglycaemic conditions measured by glucose sensor monitoring
Time frame: 2 weeks
Glucose variability as measured by glucose sensor monitoring
Time frame: 2 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 23 Mar 2020.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin in people with Diabetes Mellitus, Type 1 and Hypoglycemia, run by Radboud University Medical Center at 1 site in Netherlands.
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 7 inclusion and 18 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 23 Mar 2020. 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 Netherlands. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Symptom score in response to insulin-induced hypoglycaemia (time frame: 45 minutes). 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 23 Mar 2020.