Clinical Trial Results:
The Effect of Empagliflozin on Cardiac and Kidney Metabolism in Persons with Type 2 Diabetes
Summary
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EudraCT number |
2017-001779-22 |
Trial protocol |
DK |
Global end of trial date |
19 Dec 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Mar 2021
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First version publication date |
05 Mar 2021
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Other versions |
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Summary report(s) |
Summary and abstract |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
04.2017
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
AUH
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Sponsor organisation address |
Palle Juul-Jensens blv. , Aarhus N, Denmark, 8200
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Public contact |
Department of Endorcrinology, Aarhus University Hospital, katrine.mj@rm.dk
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Scientific contact |
Department of Endorcrinology, Aarhus University Hospital, katrine.mj@rm.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Jul 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Dec 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Dec 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Empagliflozin is a sodium–glucose cotransporter 2 (SGLT-2) inhibitor, and is used in treatment of diabetes type 2. It is previously shown that SGLT-2 inhibitors have a remarkable protective effect on the heart by reducing death caused by cardiac diseases with 38%. The reasons for these effects are still unknown, but it is known that SGLT-2 treatment increase ketogenesis. We have in a previous study found that ketone body infusion shifts cardiac metabolism towards ketone body oxidation, which possibly increases cardiac efficiency. It is also shown that SGLT-2 inhibitors have reno protective effects. The aim of this study is to examine the effects of SGLT-2 treatment by:
- Examination of substrate metabolism in heart and kidney measured by PET.
- Examination of perfusion and total energy consumption in the heart and kidney measured by PET.
- Indirect calorimetry, bloodsamples, fat- and muscle biopsies, DXA-scan, measurement of arterial stiffness and oral glucose tolerance test.
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Protection of trial subjects |
Interviews about side effects to treatment
GCP guidelines has been followed
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Background therapy |
Metformin | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Sep 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 13
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Worldwide total number of subjects |
13
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EEA total number of subjects |
13
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
6
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited through advertisements in local press in the period between September 2017 - August 2019 | ||||||||||
Pre-assignment
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Screening details |
• Age: 50-70 years • Type 2 diabetes for > 1 år • HbA1c: 48-75 mmol/mol • Metformin treatment as only anti diabetic medicin One-week walkout between study periods 23 volunteers were screened for inclusion. 13 participants were included. 1 withdraw consent due to claustrophobia during scans. | ||||||||||
Period 1
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Period 1 title |
Placebo and intervention in crossover (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||
Blinding implementation details |
Encapsulation of medicine.
Randomization and encapsulation of medicine were handled by the hospital pharmacy.
Randomization code was given after finalising data analysis
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Arms
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Arm title
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Placebo and intervention | ||||||||||
Arm description |
13 patients were randomized to receive placebo and Jardiance 25 mg in a crossover design. Both placebo and Jardiance were encapsulated. Comment: I found it necessary to choose the one arm design in this report. If I selected two arms, the number of participants were doubled. | ||||||||||
Arm type |
Placebo and intervention | ||||||||||
Investigational medicinal product name |
Jardiance
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg once daily encapsulated
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Baseline characteristics reporting groups
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Reporting group title |
Placebo and intervention in crossover
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo and intervention
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Reporting group description |
13 patients were randomized to receive placebo and Jardiance 25 mg in a crossover design. Both placebo and Jardiance were encapsulated. Comment: I found it necessary to choose the one arm design in this report. If I selected two arms, the number of participants were doubled. |
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End point title |
Cardiac uptake of free fatty acids [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
After four weeks of treatment
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis are described in the attached article (more information) |
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Attachments |
Untitled (Filename: fig2_2_columns.pdf) |
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No statistical analyses for this end point |
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End point title |
Cardiac glucose uptake [2] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
After four weeks of treatment
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis are described in the attached article (more information) |
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Attachments |
Untitled (Filename: fig2_2_columns.pdf) |
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No statistical analyses for this end point |
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End point title |
Cardiac oxygen consumption [3] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
After four weeks of treatment
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis are described in the attached article (more information) |
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Attachments |
Untitled (Filename: fig3_2_columns.pdf) |
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No statistical analyses for this end point |
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End point title |
Myocardial perfusion in rest [4] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
After four weeks of treatment
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis are described in the attached article (more information) |
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Attachments |
Untitled (Filename: fig3_2_columns.pdf) |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
09.10.2017 - 19.12.2019
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Adverse event reporting additional description |
Weekly meetings with the participants with questions regarding adverse events.
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
10.0
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Frequency threshold for reporting non-serious adverse events: 5% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No adverse events have been reported |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/33334875 |