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

NCT ID: NCT03933956

Last Updated: 2020-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-09

Study Completion Date

2020-08-01

Brief Summary

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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

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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.

Conditions

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Diabetic Nephropathies

Keywords

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Diabetic nephropathy Sodium-glucose Cotransporter 2 Inhibitors

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single-arm open-label intervention study
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Empagliflozin-treated

Oral empagliflozin tablets 10mg daily, taken for 30 days.

Group Type EXPERIMENTAL

Empagliflozin 10 MG

Intervention Type DRUG

Oral empagliflozin 10mg daily for 30 days

Interventions

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Empagliflozin 10 MG

Oral empagliflozin 10mg daily for 30 days

Intervention Type DRUG

Other Intervention Names

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Jardiance

Eligibility Criteria

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Inclusion Criteria

1. Man or woman between 21 and 100 years of age
2. Type 2 diabetes mellitus as defined by:

* Fasting plasma glucose ≥7.0mmol/l, or
* Symptoms of hyperglycemia with casual plasma glucose ≥11.1 mmol/L, or
* 2-hour plasma glucose ≥11.1 mmol/l after a 75-gram oral glucose load, or
* Known type 2 diabetes mellitus diagnosed by a medical practitioner
3. Two or more measurements indicating increased urine protein excretion within 1-year

Increased urine protein excretion is defined as:
* Urine microalbumin/creatinine ratio (ACR) \> 3.3 mg/mmol creatinine or
* Urine total protein/creatinine ratio (PCR) \> 0.2 g/urine creatinine
4. Known diabetes duration \> 3 months
5. HbA1c ≤9% (within 3 months prior to enrolment)
6. Not currently treated with an SGLT-2 inhibitor, and have not received SGLT-2 inhibitor therapy within the last 10 weeks.
7. Stable diabetes therapy for at least 3months as defined as:

* No increase in dose of diabetes medications by more than two-fold or
* No new agents added within the previous 3 months
8. Stable doses of angiotensin converting enzyme (ACE) inhibitors or angiotensin AT(1)-receptor blockers (ARBs) for at least 3 months.
9. Capable of providing informed consent

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)
Minimum Eligible Age

21 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duke-NUS Graduate Medical School

OTHER

Sponsor Role collaborator

Singapore General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yun Rui Amanda Lam, MBBS MRCP

Role: PRINCIPAL_INVESTIGATOR

Singapore General Hospital

Locations

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Singapore General Hospital

Singapore, , Singapore

Site Status

Countries

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Singapore

References

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Liu JJ, Ghosh S, Kovalik JP, Ching J, Choi HW, Tavintharan S, Ong CN, Sum CF, Summers SA, Tai ES, Lim SC. Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals With Type 2 Diabetes and Kidney Disease. Kidney Int Rep. 2016 Dec 16;2(3):470-480. doi: 10.1016/j.ekir.2016.12.003. eCollection 2017 May.

Reference Type BACKGROUND
PMID: 29142974 (View on PubMed)

Sharma K, Karl B, Mathew AV, Gangoiti JA, Wassel CL, Saito R, Pu M, Sharma S, You YH, Wang L, Diamond-Stanic M, Lindenmeyer MT, Forsblom C, Wu W, Ix JH, Ideker T, Kopp JB, Nigam SK, Cohen CD, Groop PH, Barshop BA, Natarajan L, Nyhan WL, Naviaux RK. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol. 2013 Nov;24(11):1901-12. doi: 10.1681/ASN.2013020126. Epub 2013 Oct 10.

Reference Type BACKGROUND
PMID: 23949796 (View on PubMed)

Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, Sarigianni M, Matthews DR, Tsapas A. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013 Aug 20;159(4):262-74. doi: 10.7326/0003-4819-159-4-201308200-00007.

Reference Type BACKGROUND
PMID: 24026259 (View on PubMed)

Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14.

Reference Type BACKGROUND
PMID: 27299675 (View on PubMed)

Perrone-Filardi P, Avogaro A, Bonora E, Colivicchi F, Fioretto P, Maggioni AP, Sesti G, Ferrannini E. Mechanisms linking empagliflozin to cardiovascular and renal protection. Int J Cardiol. 2017 Aug 15;241:450-456. doi: 10.1016/j.ijcard.2017.03.089. Epub 2017 Mar 23.

Reference Type BACKGROUND
PMID: 28395981 (View on PubMed)

Mudaliar S, Alloju S, Henry RR. Can a Shift in Fuel Energetics Explain the Beneficial Cardiorenal Outcomes in the EMPA-REG OUTCOME Study? A Unifying Hypothesis. Diabetes Care. 2016 Jul;39(7):1115-22. doi: 10.2337/dc16-0542.

Reference Type BACKGROUND
PMID: 27289124 (View on PubMed)

Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, Broedl UC, Woerle HJ. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014 Feb;124(2):499-508. doi: 10.1172/JCI72227. Epub 2014 Jan 27.

Reference Type BACKGROUND
PMID: 24463454 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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Duke-NUS-TIDR/2018/0010

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

MEDiaN2018

Identifier Type: -

Identifier Source: org_study_id