Posttransplant Diabetes MellitusPhase 2EMPTRA-DMNCT03113110
Empagliflozin in Post-Transplantation Diabetes Mellitus
A Phase 2 study testing Empagliflozin 10 mg in people with Posttransplant Diabetes Mellitus, run by Medical University of Vienna at 1 site in Austria.
Trial summary
RELEVANCE: Up to 50% of patients without previously known disorders of glucose metabolism develop posttransplantation diabetes mellitus (PTDM) after renal transplantation, which is associated with cardiovascular events. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Posttransplant Diabetes Mellitus
- What is being tested?
- Empagliflozin 10 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteAustria
- Study dates
- 15 Jan 2017to 31 May 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed PTDM defined as: A transplant patient requiring antidiabetic therapy, based on a previous 2-hour plasma glucose level ≥ 200 mg/dL in the OGTT (75mg glucose), based on previous blood glucose levels ≥ 200 mg/dL during random controls or based on fasting glucose levels ≥ 125 mg/dL twice or HbA1c ≥ 6.5%
- Stable graft function for more than 6 months post transplantation (eGFR ≥ 30 ml/min/1.73m2)
- At least 6 months of standard of care antidiabetic therapy (usually basal insulin) for PTDM
Who cannot join
- Age< 18 years
- Patients with prior history of type 1 or type 2 diabetes
- Pregnancy
- Severe renal impairment (GFR < 30 mL/min./1.73 m2)
- Severe blood glucose elevation with the need for therapy with insulin > 40 IU/day or HbA1c >8.5%
Trial locations and contacts
1 site in 1 country.
Austria1 site
Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria
Vienna, 1090
About this study
RELEVANCE:
Up to 50% of patients without previously known disorders of glucose metabolism develop posttransplantation diabetes mellitus (PTDM) after renal transplantation, which is associated with cardiovascular events. Although PTDM is triggered by immunosuppressive agents (calcineurin inhibitors, glucocorticoids), there is consensus against switching patients from potent tacrolimus to the less diabetogenic cyclosporin. Full-blown PTDM must therefore be treated aggressively. Empagliflozin inhibits sodium-glucose cotransporter 2 in the proximal tubule of the kidney and dramatically reduced cardiovascular risk in type 2 diabetics in a recent randomized trial. Especially in diabetics with impaired renal function, empagliflozin was safe, well tolerated, and effective against hyperglycemia and against high blood pressure. Data on SGLT2 inhibition after transplantation are completely lacking. Therefore, the potential antidiabetic of choice is currently withheld from the vulnerable PTDM population.
Read more
METHODS, STUDY DESIGN:
Prospective, single-center, non-inferiority study. Inclusion criteria: PTDM (antidiabetic therapy ≥6 months, based on prior 2-h BG ≥200 mg/dL, fasting BG ≥125 mg/dL (2 times) or HbA1c ≥6.5%); stable renal allograft function >6 months; eGFR ≥30 mL/min/1.73m2. Most important exclusion criteria: type 1 and 2 diabetes; insulin demand >40 IU/day; HbA1c >8.5%. After study inclusion, patients will record 4 weeks of 4-times daily BG measurements before undergoing an OGTT, lab work and urine analysis (including ketones, urinary culture). Empagliflozin (10 mg) will be started and insulin discontinued within 3 days. Patients will be asked to perform urinary dipstick tests at home (i.e. ketones), and to continue recording BG. Study visits at 2 and 4 weeks (second OGTT + lab work (as above)). If control over hyperglycemia is insufficient, insulin therapy will be added back, otherwise study patients remain on empagliflozin monotherapy for 1 year. Statistics will include the paired t-test.
Read the detailed description
The clinical trial plans to include 16 patients with stable renal allograft function, stable immunosuppressive therapy and PTDM, under standard antidiabetic therapy (exogenous insulin <40 IU). The sample size is based on a calculation assuming non-inferiority of empagliflozin monotherapy in comparison to previous insulin therapy, with respect to the primary endpoint: 2-hour blood glucose (2-h BG) during an oral glucose tolerance test (OGTT) immediately prior and 1 month after the start of empagliflozin monotherapy. The null hypothesis will be accepted if the average change in 2-h BG from the first to the second OGTT exceeds 30 mg/dL (empagliflozin will be inferior). Secondary endpoints comprise the average change in insulin secretory capacity and insulin sensitivity, derived from the first to the second OGTT, the average change in HbA1c at 3 months and at 1 year, compared to baseline, changes in body weight, fluid overload (determined by bioimpedance spectroscopy) and blood pressure. Safety endpoints include clinically concerning hyperglycemia after discontinuation of exogenous insulin, ketoacidosis, urinary tract infections and genital infections, worsening of renal function, hypoglycemia, hospitalizations, cardiovascular events and death. The effect of empagliflozin on the renin-angiotensin system is part of an OeNB-funded project in non-transplanted patients and will be included in the analyses of the present study.
- Conditions
- Posttransplant Diabetes Mellitus
- Being tested
- Empagliflozin 10 mg
- Keywords
- Empagliflozin, SGLT-2 Inhibition, Glucose Metabolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 mgDrug
Also called Jardiance
PTDM patients on previous antidiabetic treatment (<40 IU insulin (in some cases plus oral antidiabetics)) receive Empagliflozin, ideally as monotherapy
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin Arm | Other | Posttransplant Diabetes Mellitus (PTDM) patients after kidney transplantation receiving Empagliflozin 10 MG [Jardiance] Receives: Drug: Empagliflozin 10 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
OGTT-derived 2-hour blood glucose level
Mean change from baseline blood glucose levels of the 2h value after OGTT (75g glucose) after 1 month of empagliflozin monotherapy. Maximum tolerable change from baseline blood glucose levels should not exceed 30 mg/dL on average (100 mg/dL in each individual).
Measured: 4 weeks after start of Empagliflozin treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2017
- Study start15 Jan 2017
- Primary completion13 Jun 2017
- Study completion31 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Posttransplant Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Assoc. Prof. Dr. Manfred Hecking, MD PhD, Medical University of Vienna
- Investigators
- Manfred Hecking, MD, Principal investigator, Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03113110
- Sponsor's protocol ID
- EUDRACT-Nr: 2016-001580-37
- Other IDs
- EK-No. 1366/2016
- Acronym
- EMPTRA-DM
- Status last verified
- May 2019
- First submitted
- 8 Apr 2017
- Last updated
- 7 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schwaiger E, Burghart L, Signorini L, Ristl R, Kopecky C, Tura A, Pacini G, Wrba T, Antlanger M, Schmaldienst S, Werzowa J, Saemann MD, Hecking M. Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety. Am J Transplant. 2019 Mar;19(3):907-919. doi: 10.1111/ajt.15223. Epub 2019 Jan 25.
PubMed 30585690
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Empagliflozin in Post-Transplantation Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT03113110
- Acronym / sponsor ID
- EMPTRA-DM / EUDRACT-Nr: 2016-001580-37
- Conditions
- Posttransplant Diabetes Mellitus
- Keywords
- Empagliflozin, SGLT-2 Inhibition, Glucose Metabolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- 15 Jan 2017 (actual)
- Primary completion
- 13 Jun 2017 (actual)
- Study completion
- 31 May 2018 (actual)
- First posted
- 13 Apr 2017 (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.
RELEVANCE:
Up to 50% of patients without previously known disorders of glucose metabolism develop posttransplantation diabetes mellitus (PTDM) after renal transplantation, which is associated with cardiovascular events. Although PTDM is triggered by immunosuppressive agents (calcineurin inhibitors, glucocorticoids), there is consensus against switching patients from potent tacrolimus to the less diabetogenic cyclosporin. Full-blown PTDM must therefore be treated aggressively. Empagliflozin inhibits sodium-glucose cotransporter 2 in the proximal tubule of the kidney and dramatically reduced cardiovascular risk in type 2 diabetics in a recent randomized trial. Especially in diabetics with impaired renal function, empagliflozin was safe, well tolerated, and effective against hyperglycemia and against high blood pressure. Data on SGLT2 inhibition after transplantation are completely lacking. Therefore, the potential antidiabetic of choice is currently withheld from the vulnerable PTDM population.
METHODS, STUDY DESIGN:
Prospective, single-center, non-inferiority study. Inclusion criteria: PTDM (antidiabetic therapy ≥6 months, based on prior 2-h BG ≥200 mg/dL, fasting BG ≥125 mg/dL (2 times) or HbA1c ≥6.5%); stable renal allograft function >6 months; eGFR ≥30 mL/min/1.73m2. Most important exclusion criteria: type 1 and 2 diabetes; insulin demand >40 IU/day; HbA1c >8.5%. After study inclusion, patients will record 4 weeks of 4-times daily BG measurements before undergoing an OGTT, lab work and urine analysis (including ketones, urinary culture). Empagliflozin (10 mg) will be started and insulin discontinued within 3 days. Patients will be asked to perform urinary dipstick tests at home (i.e. ketones), and to continue recording BG. Study visits at 2 and 4 weeks (second OGTT + lab work (as above)). If control over hyperglycemia is insufficient, insulin therapy will be added back, otherwise study patients remain on empagliflozin monotherapy for 1 year. Statistics will include the paired t-test.
Detailed description
The clinical trial plans to include 16 patients with stable renal allograft function, stable immunosuppressive therapy and PTDM, under standard antidiabetic therapy (exogenous insulin <40 IU). The sample size is based on a calculation assuming non-inferiority of empagliflozin monotherapy in comparison to previous insulin therapy, with respect to the primary endpoint: 2-hour blood glucose (2-h BG) during an oral glucose tolerance test (OGTT) immediately prior and 1 month after the start of empagliflozin monotherapy. The null hypothesis will be accepted if the average change in 2-h BG from the first to the second OGTT exceeds 30 mg/dL (empagliflozin will be inferior). Secondary endpoints comprise the average change in insulin secretory capacity and insulin sensitivity, derived from the first to the second OGTT, the average change in HbA1c at 3 months and at 1 year, compared to baseline, changes in body weight, fluid overload (determined by bioimpedance spectroscopy) and blood pressure. Safety endpoints include clinically concerning hyperglycemia after discontinuation of exogenous insulin, ketoacidosis, urinary tract infections and genital infections, worsening of renal function, hypoglycemia, hospitalizations, cardiovascular events and death. The effect of empagliflozin on the renin-angiotensin system is part of an OeNB-funded project in non-transplanted patients and will be included in the analyses of the present study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin Arm | Other | Drug: Empagliflozin 10 mgPosttransplant Diabetes Mellitus (PTDM) patients after kidney transplantation receiving Empagliflozin 10 MG [Jardiance] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosed PTDM defined as: A transplant patient requiring antidiabetic therapy, based on a previous 2-hour plasma glucose level ≥ 200 mg/dL in the OGTT (75mg glucose), based on previous blood glucose levels ≥ 200 mg/dL during random controls or based on fasting glucose levels ≥ 125 mg/dL twice or HbA1c ≥ 6.5%
- Stable graft function for more than 6 months post transplantation (eGFR ≥ 30 ml/min/1.73m2)
- At least 6 months of standard of care antidiabetic therapy (usually basal insulin) for PTDM
Key exclusion criteria (5 listed)
- Age< 18 years
- Patients with prior history of type 1 or type 2 diabetes
- Pregnancy
- Severe renal impairment (GFR < 30 mL/min./1.73 m2)
- Severe blood glucose elevation with the need for therapy with insulin > 40 IU/day or HbA1c >8.5%
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 10 mgAlso: JardiancePTDM patients on previous antidiabetic treatment (<40 IU insulin (in some cases plus oral antidiabetics)) receive Empagliflozin, ideally as monotherapy | Drug | Empagliflozin Arm |
Primary outcome
OGTT-derived 2-hour blood glucose level
Time frame: 4 weeks after start of Empagliflozin treatment
Mean change from baseline blood glucose levels of the 2h value after OGTT (75g glucose) after 1 month of empagliflozin monotherapy. Maximum tolerable change from baseline blood glucose levels should not exceed 30 mg/dL on average (100 mg/dL in each individual).
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 7 May 2019.
- Derived from this study: PubMed 30585690Schwaiger E, Burghart L, Signorini L, Ristl R, Kopecky C, Tura A, Pacini G, Wrba T, Antlanger M, Schmaldienst S, Werzowa J, Saemann MD, Hecking M. Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety. Am J Transplant. 2019 Mar;19(3):907-919. doi: 10.1111/ajt.15223. Epub 2019 Jan 25.
- 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.
Manfred Hecking, MD principal investigator
Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria
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 Empagliflozin 10 mg in people with Posttransplant Diabetes Mellitus, run by Medical University of Vienna at 1 site in Austria.
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 3 inclusion and 5 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 7 May 2019. 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 Austria. 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 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?
OGTT-derived 2-hour blood glucose level (time frame: 4 weeks after start of Empagliflozin treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03113110, which also lists 1 linked publication.
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 7 May 2019.