Metabolic Effects of the SGLT-2 Inhibitor Empagliflozin in Patients With Diabetic Nephropathy (MEDiaN)

Phase 3

Terminated

• Conditions: Diabetic Nephropathies
• Interventions: Drug: Empagliflozin 10 MG

• Registration Number: NCT03933956
• Lead Sponsor: Singapore General Hospital

Brief Summary

The MEDiaN study aims to examine the state of fuel metabolism in participants with diabetic nephropathy (DN) before and after the use of the sodium-glucose transport protein 2 inhibitor (SGLT-2i) empagliflozin. The goals of the MEDiaN study are to better understand the contribution of fuel metabolism to the development of DN, and to determine if changes to fuel metabolism can have a positive impact on this disease.

The MEDiaN study is a single-center single-arm open-label intervention study to examine the effects of empagliflozin 10mg daily taken for 30 days on fuel oxidation patterns in participants with type 2 diabetes and DN.

Detailed Description

Diabetic nephropathy (DN) is a common cause of end-stage renal disease. MEDiaN study investigators hypothesize that dysregulated mitochondrial fuel oxidation is a major driver of diabetic nephropathy. The sodium-glucose transport protein 2 inhibitor (SGLT-2i) empagliflozin has been shown to slow the progression of DN in patients with diabetes.

The MEDiaN study aims to examine the state of fuel metabolism in participants with DN before and after the use of the SGLT-2i empagliflozin. The goals of the MEDiaN study are to better understand the contribution of fuel metabolism to the development of DN, and to determine if changes to fuel metabolism can have a positive impact on this disease.

The MEDiaN study is a single-center single-arm open-label intervention study to examine the effects of empagliflozin 10mg daily taken for 30 days on fuel oxidation patterns in participants with type 2 diabetes and DN.

The MEDiaN study plans to recruit 40 participants aged 21 to 100 years of age with type 2 diabetes mellitus and diabetic nephropathy. Participants will receive treatment with oral empagliflozin 10mg daily for 30 days. The state of fuel metabolism will be examined through metabolomics analysis of blood and urine samples before and after empagliflozin 10mg daily taken for 30 days.

Study Timeline

• Study First Submitted: 2019-04-20
• Study First Submitted QC: 2019-04-28
• Study First Posted: 2019-05-01
• Study Start: 2020-01-09
• Primary Completion: 2020-08-01
• Study Completion: 2020-08-01
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-13
• Last Update Posted: 2020-12-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

Not provided

Exclusion Criteria

1. Type 1 diabetes mellitus
2. Ketosis-prone diabetes
3. Previous diabetic ketoacidosis
4. History of Fournier's gangrene or skin and soft tissue infections of the perineum
5. Recurrent or severe urinary tract or genital mycotic infections, or history of genitourinary infection within 2 weeks prior to informed consent
6. Significant renal impairment (estimated Glomerular Filtration Rate < 45 ml/min/1.73m2**)
7. Dialysis or kidney transplant
8. Renal artery stenosis
9. Alanine aminotransferase or aspartate aminotransferase above 3x upper limit of normal
10. Significant change in weight (≥10% in the preceding 6 months)
11. Treatment with anti-obesity drugs
12. Previous bariatric surgery or other gastrointestinal surgeries that induce chronic malabsorption
13. Treatment with systemic glucocorticoids
14. Blood dyscrasias or clinically significant anaemia (Haemoglobin < 10 g/L)
15. Medical condition likely to limit survival to less than 3 years
16. Uncontrolled thyrotoxicosis, untreated hypothyroidism
17. Any ongoing acute medical illnesses
18. Hospitalization within 1 month prior to enrolment
19. Nursing mothers
20. Pregnancy, currently trying to become pregnant, or of child-bearing potential and not practicing an acceptable method of birth control or do not plan to continue using this method throughout the study
21. Excessive alcohol intake (> 1 unit per day for women and > 2 units per day for men)
22. History of drug abuse
23. Pancreatic insulin deficiency from any cause (history of pancreatitis, pancreatic surgery)
24. Known intolerance or allergic reactions to empagliflozin or other SGLT-2 inhibitors
25. Current participation in another clinical trial, or ingestion of investigational drug in another trial within 30 days prior to enrolment.
26. Presence of any non-DN renal glomerular disease (e.g. IgA nephropathy, lupus nephritis, membranous glomerulonephritis, focal segmental glomerular sclerosis)
27. Any previous organ transplantation
28. Any factors likely to limit adherence to interventions (e.g. dementia; alcohol or substance abuse; history of unreliability in medication taking or appointment keeping; significant concerns about participation in the study from spouse, significant other or family members)
29. Failure to obtain informed consent from participant
30. Presence of postural hypotension or clinically significant dehydration (reduced skin turgor, dry oral mucosa, hypotension)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Empagliflozin-treated	Empagliflozin 10 MG	Oral empagliflozin tablets 10mg daily, taken for 30 days.

Primary Outcome Measures

Name	Time	Method
Change in ketone signature	Baseline and after 30 days of treatment with empagliflozin 10mg daily	Change in ketone signature following 30 days of empagliflozin treatment
Change in amino acid metabolome signature	Baseline and after 30 days of treatment with empagliflozin 10mg daily	Change in amino acid metabolome signature following 30 days of empagliflozin treatment
Change in lipid metabolome signature	Baseline and after 30 days of treatment with empagliflozin 10mg daily	Change in lipid metabolome signature following 30 days of empagliflozin treatment

Trial Locations

Locations (1)

Singapore General Hospital; 🇸🇬 Singapore, Singapore