Type 1 DiabetesPhase 1Dapa-StressNCT04234867
Study to Explore the Effect of Dapagliflozin and Stress in Adolescent and Adult Subjects With Type 1 Diabetes (T1D)
A Phase 1 study testing Dapagliflozin and Stress in people with Type 1 Diabetes and Diabetic Ketoacidosis, run by Kinderkrankenhaus auf der Bult at 1 site in Germany.
Trial summary
Type 1 Diabetes is characterized by an absolute lack of insulin caused by autoimmune ß-cell destruction. Looking for different therapeutic approaches, beyond the administration of Insulin SGLT-Inhibitors (SGLT=sodium-glucose cotransporter) like Dapagliflozin look like a promising option to avoid hyperglycaemic… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Type 1 Diabetes, Diabetic Ketoacidosis
- What is being tested?
- Dapagliflozin and Stress
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteGermany
- Study dates
- 18 May 2022to 26 Aug 2022
- Phase
- Phase 1
- 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 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Provision of informed consent from participant and all legal representatives prior to any study specific procedures
- Age: Female and/or male aged >18 years
- Subject must have type 1 diabetes (as diagnosed clinically) ≥ 12 months
- HbA1c <10 %
- Insulin use with an average daily dose between 0.6 - 2.0 U/kg administered by insulin pump (CSII)
- BMI 23.0 to 35.0 kg/m2 minimum weight of 50 kg
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- Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study as judged by the investigator
- WOCBP must have a negative serum pregnancy test at screening as well as negative urine tests at follow up visits
- Women must not be breastfeeding
Who cannot join
- Target Disease Exclusions
- History of T2DM (type 2 diabetes mellitus), maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis
- Any use of oral hypoglycemic agents within 2 weeks prior to the screening visit
- History of diabetes ketoacidosis (DKA) within 12 weeks prior to prior to the screening visit
- History of diabetes insipidus
- History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 3 months prior to prior to the screening visit
Show all 20Show fewer
- Frequent episodes of hypoglycemia as defined by more than one episode requiring assistance, emergency care (paramedics or emergency room care) or glucagon therapy (in children defined as seizure or loss of consciousness) , or more than 2 unexplained episodes of symptomatic hypoglycemia within 3 months prior to the screening visit.
- An unexplained event is defined as an event that cannot be explained by circumstances such as dietary (e.g. missed meal), strenuous exercise, error in insulin dosing, etc.
- Hypoglycemic unawareness
- History of Addison's disease or chronic adrenal insufficiency
- Physical and Laboratory Test Findings
- Random C-Peptide >0.5 nmol/l
- Aspartate aminotransferase (AST) > 2X Upper limit of normal (ULN)
- Alanine aminotransferase (ALT) > 2X ULN
- Serum total bilirubin > 2X ULN (except known Gilbert's disease)
- Creatine kinase (CK) > 3X ULN
- Estimated GFR (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula ≤ 60 ml/min/1.73m2. The renal function, eGFR will be estimated by the abbreviated MDRD, using laboratory measurements of serum creatinine collected at screening
- Hemoglobin ≤ 11.0 g/dl (110 g/l) for men; hemoglobin ≤10.0 g/dl (100 g/L) for women.
- Positive for hepatitis B surface antigen or anti-hepatitis C virus antibody or HIV in patient's history.
- Abnormal Free T4 Note: abnormal TSH value at screening will be further evaluated for free T4.Subjects with abnormal free T4 values will be excluded. A one-time retest may be allowed, as determined by the Investigator, after a minimum of 6 weeks following the adjustment of thyroid hormone replacement therapy in subject who have had a prior diagnosis of a thyroid disorder and who are currently receiving thyroid replacement therapy. Such cases should be discussed with the Sponsor prior to re-testing. The subject must have all screening procedures and laboratory assessments performed as part of this re-test, and all of these must meet enrolment eligibility criteria. The subject's number will, however, remain the same as initially assigned.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Kinder- und Jugendkrankenhaus AUF DER BULT
Hanover, Lower Saxony, 30173
About this study
Official title: A Randomized, Double-Blinded, Placebo-controlled, Single-center Phase 1 Pilot Study to Explore the Effect of DAPAglifozin and Stress ( i.v. ACTH) on the Development of DKA After Insulin Withdrawal in Adolescent and Adult Subjects With T1D
Type 1 Diabetes is characterized by an absolute lack of insulin caused by autoimmune ß-cell destruction. Looking for different therapeutic approaches, beyond the administration of Insulin SGLT-Inhibitors (SGLT=sodium-glucose cotransporter) like Dapagliflozin look like a promising option to avoid hyperglycaemic excursions which are a reason for glycaemic variability by renal excretion of excessive glucose without administration of extra insulin. But also euglycemic DKA has been reported during SGLT2 add-on therapy to insulin in T1D and mechanistic studies have been called for.
The role of Dapagliflozin-induced hyperglucagonemia and stress/infection precipitating euglycemic DKA in this situation is unclear.
Read more
Thus the purpose of this pilot study is to collect clinical data on the development of DKA after insulin-withdrawal with Dapagliflozin compared to placebo and the added effect of a single dose of 4mg/kg i.v. ACTH as mediator of stress.
The first objective is to investigate the time to DKA (defined as Bicarbonate <19 mmol/l) after insulin withdrawal during treatment with a stable 5 day single daily dose of 10mg Dapagliflozin in patients with type 1 Diabetes.
In addition it should be evaluate the additional effect of stress, modelled by a single injection of ACTH on DKA development during Dapagliflozin Treatment.
We also want to know if Dapagliflozin influences glucagon levels during insulin withdrawal and how this is associated with the time course of DKA development.
Read the detailed description
The purpose of the Dapastress trial is, to evaluate if some metabolic parameters can be identified as an early marker or contributor in development of ketonic metabolic imbalance. As the hormonal "background" is completely different in pubertal adolescents compared to adults (especially contra-insulin hormones as growth hormone, glucagon).
Approximately 20 subjects 18-45 years will be screened in order to randomize 16 patients, where stress and Dapagliflozin (or corresponding placebo) will be administered independently.
The trial will consist of 14 visits: a screening visit (Visit 1), 4 overnight visits complexes (Visit 2 to Visit 13), including phone visits and a follow-up visit (Visit 14). Furthermore, an information visit will take place prior to the screening visit in order to obtain patient's informed consent. Screening will take place 2-21 days prior to Visit 2. The follow-up visit will take place 5-21 days after the end of Visit 13. The overnight visits will be separated by a wash-out period (5-30 days between the end of each visit complex and start of next complex) during which the subjects will resume their normal insulin treatment. Each phone visit will take place 3-5 days after the end of overnight Visits.
The planned total duration of the trial is 58-100 days per subject (rescheduled visits excluded). Each subject will be randomised to a unique treatment sequence (1:1:1:1).
Seq 1: A D B C Seq 2: B A C D Seq 3: C B D A Seq 4: D C A B (e.g. A Dapa-Stress, B Dapa-Placebo Stress , C Placebo- Stress, D Placebo-Placebo Stress)
After randomization patients will receive Dapagliflozin/placebo for 5 single daily Dosis. During the overnight visits the metabolic control will be achieved by a variable i.v. Infusion of human Insulin by an Infusion pump. The procedure will be used in order to aim and maintain blood glucose levels between 70 and 180 mg/dl. The fluid Infusion and Insulin dosing scheme will depend on Body weight and blood glucose levels. At approximately 03:00 hours in the morning the blood glucose should be within target range. Then insulin infusion will be suspended. In the morning the last dose of actual study medication (Dapagliflozin/ Placebo) and the single dose of stress (ACTH or placebo) will be administered. During now started stress phase blood samples for determination of metabolic Panels,blood gas analysis, Glucose and ketone will be taken hourly and vital signs tested. 12 hours after administration of stress (ACTH or placebo) the patients will resume their CSII and will be discharged when being well on investigator's judgement.
- Conditions
- Type 1 Diabetes, Diabetic Ketoacidosis
- Being tested
- Dapagliflozin, Placebo oral tablet, Stress, Placebo Stress
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetic Ketoacidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
Also called Forxiga
once daily for 5 days
Placebo oral tabletDrug
Also called Control
once daily for 5 days
StressOther
Also called Synacthen
single dose after last administration of experimental drug
Placebo StressOther
Also called Stress Control
single dose after last administration of experimental drug
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin - Stress | Experimental | Administration of 10mg dapagliflozin oral for 5 days and one i.v. administration of 250µg ACTH (Synacthen) Receives: Drug: Dapagliflozin; Other: Stress |
| Dapagliflozin and Placebo Stress | Experimental | Administration of 10mg dapagliflozin oral for 5 days and one i.v. administration of Placebo matching Synacthen Receives: Drug: Dapagliflozin; Other: Placebo Stress |
| Placebo Dapagliflozin and Stress | Placebo comparator | Administration of placebo oral for 5 days identical to dapagliflozin and one i.v. administration of 250µg ACTH (Synacthen) Receives: Drug: Placebo oral tablet; Other: Stress |
| Placebo Dapagliflozin and Placebo Stress | Placebo comparator | Administration of placebo oral for 5 days identical to dapagliflozin and one i.v. administration of Placebo matching Synacthen Receives: Drug: Placebo oral tablet; Other: Placebo Stress |
What is being measured
The primary outcome is the main question the study is designed to answer.
time to development of DKA
time from Insulin withdrawal to development of DKA (defined as HCO3 -< 19mmol/L)
Measured: 12 hours
Secondary outcomes (1)
time to decrease of ph level
time from Insulin withdrawal to decrease of pH < 7.30
Measured: 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2020
- Study start18 May 2022
- Primary completion26 Aug 2022
- Study completion26 Aug 2022
Why it stopped: slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kinderkrankenhaus auf der Bult
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Torben Biester, MD, Principal investigator, Kinderkrankenhaus auf der Bult
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04234867
- Sponsor's protocol ID
- ESR-17-13152
- Acronym
- Dapa-Stress
- Status last verified
- Dec 2024
- First submitted
- 16 Jan 2020
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blinded, Placebo-controlled, Single-center Phase 1 Pilot Study to Explore the Effect of DAPAglifozin and Stress ( i.v. ACTH) on the Development of DKA After Insulin Withdrawal in Adolescent and Adult Subjects With T1D
- ClinicalTrials.gov ID
- NCT04234867
- Acronym / sponsor ID
- Dapa-Stress / ESR-17-13152
- Conditions
- Type 1 Diabetes, Diabetic Ketoacidosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow recruitment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Kinderkrankenhaus auf der BultUniversity, hospital or other
- Study start
- 18 May 2022 (actual)
- Primary completion
- 26 Aug 2022 (actual)
- Study completion
- 26 Aug 2022 (actual)
- First posted
- 21 Jan 2020 (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.
Type 1 Diabetes is characterized by an absolute lack of insulin caused by autoimmune ß-cell destruction. Looking for different therapeutic approaches, beyond the administration of Insulin SGLT-Inhibitors (SGLT=sodium-glucose cotransporter) like Dapagliflozin look like a promising option to avoid hyperglycaemic excursions which are a reason for glycaemic variability by renal excretion of excessive glucose without administration of extra insulin. But also euglycemic DKA has been reported during SGLT2 add-on therapy to insulin in T1D and mechanistic studies have been called for.
The role of Dapagliflozin-induced hyperglucagonemia and stress/infection precipitating euglycemic DKA in this situation is unclear.
Thus the purpose of this pilot study is to collect clinical data on the development of DKA after insulin-withdrawal with Dapagliflozin compared to placebo and the added effect of a single dose of 4mg/kg i.v. ACTH as mediator of stress.
The first objective is to investigate the time to DKA (defined as Bicarbonate <19 mmol/l) after insulin withdrawal during treatment with a stable 5 day single daily dose of 10mg Dapagliflozin in patients with type 1 Diabetes.
In addition it should be evaluate the additional effect of stress, modelled by a single injection of ACTH on DKA development during Dapagliflozin Treatment.
We also want to know if Dapagliflozin influences glucagon levels during insulin withdrawal and how this is associated with the time course of DKA development.
Detailed description
The purpose of the Dapastress trial is, to evaluate if some metabolic parameters can be identified as an early marker or contributor in development of ketonic metabolic imbalance. As the hormonal "background" is completely different in pubertal adolescents compared to adults (especially contra-insulin hormones as growth hormone, glucagon).
Approximately 20 subjects 18-45 years will be screened in order to randomize 16 patients, where stress and Dapagliflozin (or corresponding placebo) will be administered independently.
The trial will consist of 14 visits: a screening visit (Visit 1), 4 overnight visits complexes (Visit 2 to Visit 13), including phone visits and a follow-up visit (Visit 14). Furthermore, an information visit will take place prior to the screening visit in order to obtain patient's informed consent. Screening will take place 2-21 days prior to Visit 2. The follow-up visit will take place 5-21 days after the end of Visit 13. The overnight visits will be separated by a wash-out period (5-30 days between the end of each visit complex and start of next complex) during which the subjects will resume their normal insulin treatment. Each phone visit will take place 3-5 days after the end of overnight Visits.
The planned total duration of the trial is 58-100 days per subject (rescheduled visits excluded). Each subject will be randomised to a unique treatment sequence (1:1:1:1).
Seq 1: A D B C Seq 2: B A C D Seq 3: C B D A Seq 4: D C A B (e.g. A Dapa-Stress, B Dapa-Placebo Stress , C Placebo- Stress, D Placebo-Placebo Stress)
After randomization patients will receive Dapagliflozin/placebo for 5 single daily Dosis. During the overnight visits the metabolic control will be achieved by a variable i.v. Infusion of human Insulin by an Infusion pump. The procedure will be used in order to aim and maintain blood glucose levels between 70 and 180 mg/dl. The fluid Infusion and Insulin dosing scheme will depend on Body weight and blood glucose levels. At approximately 03:00 hours in the morning the blood glucose should be within target range. Then insulin infusion will be suspended. In the morning the last dose of actual study medication (Dapagliflozin/ Placebo) and the single dose of stress (ACTH or placebo) will be administered. During now started stress phase blood samples for determination of metabolic Panels,blood gas analysis, Glucose and ketone will be taken hourly and vital signs tested. 12 hours after administration of stress (ACTH or placebo) the patients will resume their CSII and will be discharged when being well on investigator's judgement.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin - Stress | Experimental | Drug: Dapagliflozin, Other: StressAdministration of 10mg dapagliflozin oral for 5 days and one i.v. administration of 250µg ACTH (Synacthen) |
| Dapagliflozin and Placebo Stress | Experimental | Drug: Dapagliflozin, Other: Placebo StressAdministration of 10mg dapagliflozin oral for 5 days and one i.v. administration of Placebo matching Synacthen |
| Placebo Dapagliflozin and Stress | Placebo comparator | Drug: Placebo oral tablet, Other: StressAdministration of placebo oral for 5 days identical to dapagliflozin and one i.v. administration of 250µg ACTH (Synacthen) |
| Placebo Dapagliflozin and Placebo Stress | Placebo comparator | Drug: Placebo oral tablet, Other: Placebo StressAdministration of placebo oral for 5 days identical to dapagliflozin and one i.v. administration of Placebo matching Synacthen |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Provision of informed consent from participant and all legal representatives prior to any study specific procedures
- Age: Female and/or male aged >18 years
- Subject must have type 1 diabetes (as diagnosed clinically) ≥ 12 months
- HbA1c <10 %
- Insulin use with an average daily dose between 0.6 - 2.0 U/kg administered by insulin pump (CSII)
Key exclusion criteria (20 listed)
- Target Disease Exclusions
- An unexplained event is defined as an event that cannot be explained by circumstances such as dietary (e.g. missed meal), strenuous exercise, error in insulin dosing, etc.
- Physical and Laboratory Test Findings
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: Forxigaonce daily for 5 days | Drug | Dapagliflozin - Stress, Dapagliflozin and Placebo Stress |
| Placebo oral tabletAlso: Controlonce daily for 5 days | Drug | Placebo Dapagliflozin and Placebo Stress, Placebo Dapagliflozin and Stress |
| StressAlso: Synacthensingle dose after last administration of experimental drug | Other | Dapagliflozin - Stress, Placebo Dapagliflozin and Stress |
| Placebo StressAlso: Stress Controlsingle dose after last administration of experimental drug | Other | Dapagliflozin and Placebo Stress, Placebo Dapagliflozin and Placebo Stress |
Primary outcome
time to development of DKA
Time frame: 12 hours
time from Insulin withdrawal to development of DKA (defined as HCO3 -< 19mmol/L)
1 secondary outcome
time to decrease of ph level
Time frame: 12 hours
Results and safety
The study was stopped early (reason given: slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
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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.
Torben Biester, MD principal investigator
Kinderkrankenhaus auf der Bult
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dapagliflozin and Stress in people with Type 1 Diabetes and Diabetic Ketoacidosis, run by Kinderkrankenhaus auf der Bult at 1 site in Germany.
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 9 inclusion and 20 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: stopped early, as of the sponsor's last update on 9 Dec 2024. 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 Germany. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: slow recruitment). Results are not available in the source record.
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?
time to development of DKA (time frame: 12 hours). 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 9 Dec 2024.