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Trial record 2 of 187 for:    BI10773

Empagliflozin in Post-Transplantation Diabetes Mellitus (EMPTRA-DM)

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ClinicalTrials.gov Identifier: NCT03113110
Recruitment Status : Recruiting
First Posted : April 13, 2017
Last Update Posted : April 13, 2017
Sponsor:
Information provided by (Responsible Party):
Assoc.Prof.Priv.-Doz.Dr.med Manfred Hecking, Medical University of Vienna

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Posttransplant Diabetes Mellitus Drug: Empagliflozin 10 mg Phase 2

Detailed Description:
We have designed a clinical trial that 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Empagliflozin in Post-Transplantation Diabetes Mellitus
Actual Study Start Date : January 15, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Empagliflozin Arm
Posttransplant Diabetes Mellitus (PTDM) patients after kidney transplantation receiving Empagliflozin 10 MG [Jardiance]
Drug: Empagliflozin 10 mg
PTDM patients on previous antidiabetic treatment (<40 IU insulin (in some cases plus oral antidiabetics)) receive Empagliflozin, ideally as monotherapy
Other Name: Jardiance




Primary Outcome Measures :
  1. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03113110


Contacts
Contact: Manfred Hecking, MD +43-699-10580831 manfred.hecking@meduniwien.ac.at
Contact: Elisabeth Schwaiger, MD +43-1-40400-55930 elisabeth.schwaiger@meduniwien.ac.at

Locations
Austria
Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria Recruiting
Vienna, Austria, 1090
Contact: Manfred Hecking, MD       manfred.hecking@meduniwien.ac.at   
Contact: Elisabeth Schwaiger, MD       elisabeth.schwaiger@meduniwien.ac.at   
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Manfred Hecking, MD Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria

Responsible Party: Assoc.Prof.Priv.-Doz.Dr.med Manfred Hecking, Assoc. Prof. PD. Dr.med., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT03113110     History of Changes
Other Study ID Numbers: EUDRACT-Nr: 2016-001580-37
EK-No. 1366/2016 ( Other Identifier: MUVienna Ethics Committee )
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: April 13, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assoc.Prof.Priv.-Doz.Dr.med Manfred Hecking, Medical University of Vienna:
Empagliflozin
SGLT-2 Inhibition
Glucose Metabolism

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Empagliflozin
Hypoglycemic Agents
Physiological Effects of Drugs