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Diabetic NephropathiesPhase 3(MEDiaN)NCT03933956

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

A Phase 3 study testing Empagliflozin 10 MG in people with Diabetic Nephropathies, run by Singapore General Hospital at 1 site in Singapore.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 to 100 years
Conditions the study is for
Diabetic Nephropathies
What is being tested?
Empagliflozin 10 MG
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteSingapore
Study dates
9 Jan 2020to 1 Aug 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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
Show all 18Show fewer
  • 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
  • No new agents added within the previous 3 months
  • Stable doses of angiotensin converting enzyme (ACE) inhibitors or angiotensin AT(1)-receptor blockers (ARBs) for at least 3 months.
  • Capable of providing informed consent

Who cannot join

  • 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**)
Show all 30Show fewer
  • 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
  • Uncontrolled thyrotoxicosis, untreated hypothyroidism
  • Any ongoing acute medical illnesses
  • Hospitalization within 1 month prior to enrolment
  • Nursing mothers
  • 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
  • Excessive alcohol intake (> 1 unit per day for women and > 2 units per day for men)
  • History of drug abuse
  • Pancreatic insulin deficiency from any cause (history of pancreatitis, pancreatic surgery)
  • Known intolerance or allergic reactions to empagliflozin or other SGLT-2 inhibitors
  • Current participation in another clinical trial, or ingestion of investigational drug in another trial within 30 days prior to enrolment.
  • Presence of any non-DN renal glomerular disease (e.g. IgA nephropathy, lupus nephritis, membranous glomerulonephritis, focal segmental glomerular sclerosis)
  • Any previous organ transplantation
  • 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)
  • Failure to obtain informed consent from participant
  • Presence of postural hypotension or clinically significant dehydration (reduced skin turgor, dry oral mucosa, hypotension)

Trial locations and contacts

1 site in 1 country.

Singapore1 site

  • Singapore General Hospital

    Singapore, 169608

Other trials in Singapore

About this study

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.

Read the 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.

Being tested
Empagliflozin 10 MG
Keywords
Diabetic nephropathy, Sodium-glucose Cotransporter 2 Inhibitors
Medical subject headings
Diabetic Nephropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Empagliflozin 10 MGDrug

    Also called Jardiance

    Oral empagliflozin 10mg daily for 30 days

Study groups in NCT03933956
Study groupRoleWhat they receive
Empagliflozin-treatedExperimentalOral empagliflozin tablets 10mg daily, taken for 30 days.
Receives: Drug: Empagliflozin 10 MG

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in lipid metabolome signature

    Change in lipid metabolome signature following 30 days of empagliflozin treatment

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

  2. Change in ketone signature

    Change in ketone signature following 30 days of empagliflozin treatment

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

  3. Change in amino acid metabolome signature

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2019
  2. Study start9 Jan 2020
  3. Primary completion1 Aug 2020
  4. Study completion1 Aug 2020

Why it stopped: Study terminated owing to challenges posed by the COVID-19 situation.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Model description
Single-arm open-label intervention study
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03933956
Sponsor's protocol ID
MEDiaN2018
Other IDs
Duke-NUS-TIDR/2018/0010
Acronym
(MEDiaN)
Status last verified
Dec 2020
First submitted
20 Apr 2019
Last updated
17 Dec 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29142974

  • 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.

    PubMed 23949796

  • 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.

    PubMed 24026259

  • 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.

    PubMed 27299675

  • 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.

    PubMed 28395981

  • 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.

    PubMed 27289124

  • 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.

    PubMed 24463454

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Empagliflozin 10 MG in people with Diabetic Nephropathies, run by Singapore General Hospital at 1 site in Singapore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study terminated owing to challenges posed by the COVID-19 situation.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in lipid metabolome signature (time frame: Baseline and after 30 days of treatment with empagliflozin 10mg daily). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03933956, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2020.

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