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

NCT03933956 | Terminated Phase 3

• 2 other identifiers: MEDiaN2018Duke-NUS-TIDR/2018/0010
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Nephropathies

Keywords

Diabetic nephropathy; Sodium-glucose Cotransporter 2 Inhibitors

Outcome Measures

Primary Outcomes (3)

• Change in lipid metabolome signature

  Change in lipid metabolome signature following 30 days of empagliflozin treatment

  Baseline and after 30 days of treatment with empagliflozin 10mg daily

• Change in ketone signature

  Change in ketone signature following 30 days of empagliflozin treatment

  Baseline and after 30 days of treatment with empagliflozin 10mg daily

• Change in amino acid metabolome signature

  Change in amino acid metabolome signature following 30 days of empagliflozin treatment

  Baseline and after 30 days of treatment with empagliflozin 10mg daily

Study Arms (1)

Empagliflozin-treated

EXPERIMENTAL

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

Drug: Empagliflozin 10 MG

Interventions

Empagliflozin 10 MG DRUG

Oral empagliflozin 10mg daily for 30 days

Also known as: Jardiance

Empagliflozin-treated

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman between 21 and 100 years of age
• 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
• 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
• 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
• Known diabetes duration \> 3 months
• HbA1c ≤9% (within 3 months prior to enrolment)
• Not currently treated with an SGLT-2 inhibitor, and have not received SGLT-2 inhibitor therapy within the last 10 weeks.
• Stable diabetes therapy for at least 3months as defined as:
• No increase in dose of diabetes medications by more than two-fold or

You may not qualify if:

• Type 1 diabetes mellitus
• Ketosis-prone diabetes
• Previous diabetic ketoacidosis
• History of Fournier's gangrene or skin and soft tissue infections of the perineum
• Recurrent or severe urinary tract or genital mycotic infections, or history of genitourinary infection within 2 weeks prior to informed consent
• Significant renal impairment (estimated Glomerular Filtration Rate \< 45 ml/min/1.73m2\*\*)
• Dialysis or kidney transplant
• Renal artery stenosis
• Alanine aminotransferase or aspartate aminotransferase above 3x upper limit of normal
• Significant change in weight (≥10% in the preceding 6 months)
• Treatment with anti-obesity drugs
• Previous bariatric surgery or other gastrointestinal surgeries that induce chronic malabsorption
• Treatment with systemic glucocorticoids
• Blood dyscrasias or clinically significant anaemia (Haemoglobin \< 10 g/L)
• Medical condition likely to limit survival to less than 3 years

Sponsors & Collaborators

• Singapore General Hospital: lead
• Duke-NUS Graduate Medical School: collaborator

Study Sites (1)

Singapore General Hospital

Singapore, 169608, Singapore

Location

Related Publications (7)

• 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.

  PMID: 29142974 BACKGROUND

• 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.

  PMID: 23949796 BACKGROUND

• 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.

  PMID: 24026259 BACKGROUND

• 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.

  PMID: 27299675 BACKGROUND

• 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.

  PMID: 28395981 BACKGROUND

• 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.

  PMID: 27289124 BACKGROUND

• 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.

  PMID: 24463454 BACKGROUND

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Yun Rui Amanda Lam, MBBS MRCP

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm open-label intervention study

Study Record Dates

• First Submitted: April 20, 2019
• First Posted: May 1, 2019
• Study Start: January 9, 2020
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: December 17, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)