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Type2 DiabetesPhase 4NCT02964715

The Effect of Empagliflozin on NAFLD in Asian Patients With Type 2 Diabetes

A Phase 4 study testing Empagliflozin in people with Type2 Diabetes and NAFLD, run by University of Malaya at 1 site in Malaysia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Non-Alcoholic Fatty Liver Disease( NAFLD) is common in patients with type 2 diabetes. Empagliflozin, an FDA-approved oral medication used to treat type 2 diabetes, has been shown to reduce production and deposition of fat in the liver in animal experiments. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Type2 Diabetes, NAFLD
What is being tested?
Empagliflozin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteMalaysia
Study dates
Nov 2016to Nov 2018
Phase
Phase 4
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • biopsy proven NASH
  • Type 2 DM
  • HbA1c :>6.5%
  • BMI < 45kg/m2
  • Any anti-diabetic agent except SGLT2 inhibitors, TZDs(thiazolidinediones), DPP4(Dipeptidyl peptidase4) inhibitors and GLP1 RAs(Glucagon-like Peptide 1-Receptor Agonists)

Who cannot join

  • eGFR <45 ml/min
  • structural and functional urogenital abnormalities, that predispose for urogenital infections
  • Investigational product use in the last 6 months
  • SGLT2 inhibitor, TZD, DPP4 inhibitor and GLP1 RA use within the past 6 months
  • DKA(Diabetic Ketoacidosis) or HHS(Hyperosmoloar Hyperglycaemic Syndrome) within the last 6 months
  • Pregnancy
Show all 19Show fewer
  • Presence of major contraindications to magnetic resonance imaging (cardiac pacemakers, claustrophobia, foreign bodies and implanted medical devices with ferromagnetic properties).
  • Liver cirrhosis
  • Type 1 diabetes
  • Severe uncorrected insulin insufficiency
  • Significant alcohol intake
  • HIV infection
  • Use of Traditional Chinese Medication or alternative therapies
  • Coexisting causes of chronic liver disease - chronic viral hepatitis(B \& C), autoimmune liver disease, hemochromatosis, Wilson's etc.
  • Use of medications associated with steatosis eg. Methotrexate, anticonvulsants, antiretroviral therapy etc.
  • h/o stroke
  • Steroid therapy
  • Endogenous Cushing's
  • Familial hypertriglyceridemia

Trial locations and contacts

1 site in 1 country.

Shireene R Vethakkan, MD contact

0162093355

shireene.vethakkan@gmail.com

Wah K Chan, MRCP contact

0163655232

wahkheong2003@hotmail.com

Malaysia1 site, 1 recruiting

  • University of Malaya

    Kuala Lumpur, Kuala Lumpur

    Shireene R Vethakkan, MD, 0162093355, shireene.vethakkan@gmail.com

    Wah K Chan, MRCP

    Recruiting

Other trials in Malaysia

About this study

Non-Alcoholic Fatty Liver Disease( NAFLD) is common in patients with type 2 diabetes. Empagliflozin, an FDA-approved oral medication used to treat type 2 diabetes, has been shown to reduce production and deposition of fat in the liver in animal experiments. There is little published evidence that this is so in Asian patients with type 2 diabetes. The investigators designed this pilot study to determine if use of empagliflozin for 6 months in patients with type 2 diabetes can improve scan, blood marker and biopsy features of NAFLD.

Read the detailed description

Empagliflozin, an FDA-approved SGLT2 (Sodium glucose transporter 2) inhibitor used to treat type 2 diabetes, has been shown to reduce hepatic de novo lipogenesis and hepatic steatosis in animal models. There is little published evidence that this is so in Asian patients with type 2 diabetes. The investigators designed this open label proof of concept trial to determine if use of empagliflozin for 6 months in patients with type 2 diabetes can improve biomarkers and histological features of biopsy proven NAFLD.

Hypotheses

  1. 6 months of empagliflozin will result in improved histology on liver biopsy in type 2 dm patients with NAFLD

2.6 months of empagliflozin will result in changes in liver enzymes, adipocytokines and FGF levels in type 2 dm patients with NAFLD

3.6 months of empagliflozin will result in improved liver stiffness measurement in type 2 dm patients with NAFLD

Study protocol

This is a prospective open-label proof-of-concept study. The investigators plan to recruit 25 Asian patients with biopsy-proven NASH and type 2 diabetes and commence them on empagliflozin 25 mg daily for 6 months. Upon recruitment clinical information will be obtained via an interview and use of a structured questionnaire. Anthropometric measurements will be obtained at baseline and 6 months. A repeat liver biopsy will be performed after 6 months of empagliflozin therapy. MRI and fibroscan of the liver will be conducted at baseline and 6 months. Fasting blood samples will be drawn for glucose, insulin, c-peptide, triglyceride, HDL, LDL, total cholesterol, NEFA(non-esterified fatty acid), HbA1c , liver function test(including albumin, AST, ALT, gamma GT, uric acid, inflammatory markers, FGF(fibroblast growth factor) and other biomarkers at baseline and 6 months.

Patients will be reviewed by a physician at 1 month and 6 months for development of any potential adverse events while on empagliflozin therapy.

Patients will be instructed not to make any significant changes to diet and lifestyle in these 6 months in order to assess to full effect of the intervention with no possible confounding factors.

Being tested
Empagliflozin
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

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

Study groups in NCT02964715
Study groupRoleWhat they receive
Interventional armExperimentalPatients with NAFLD and Type 2 Diabetes prescribed 25mg empagliflozin(JARDIANCE) daily for 6 months
Receives: Drug: Empagliflozin

What is being measured

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

  1. Change in histological Grade as evaluated with Non-alcoholic Steatohepatitis Clinical Research Network Scoring System

    liver biopsy

    Measured: baseline, 6 months

  2. Change in serum FGF 21

    blood test

    Measured: baseline and 6 months

Secondary outcomes (15)

  1. Change in fibroscan and elastography measure of liver stiffness

    imaging

    Measured: baseline and 6 months

  2. Change in Liver enzymes

    blood test - AST,ALT, gamma GT

    Measured: baseline and 6 months

  3. Change in steatosis

    histological

    Measured: baseline and 6 months

  4. Change in lobular inflammation

    histological

    Measured: baseline and 6 months

  5. Change in ballooning

    histological

    Measured: baseline and 6 months

  6. Change in fibrosis

    histological

    Measured: baseline and 6 months

  7. Change in metabolic outcome -HbA1c

    serum concentration

    Measured: baseline and 6 months

  8. Change in metabolic outcome - fasting NEFA

    serum concentration

    Measured: baseline and 6 months

  9. Change in metabolic outcome - fasting Tg

    serum concentration

    Measured: baseline and 6 months

  10. Change in serum FGF 19

    serum concentration

    Measured: baseline and 6 months

  11. Change in serum adiponectin

    serum concentration

    Measured: baseline and 6 months

  12. Change in serum IL-6

    serum concentration

    Measured: baseline and 6 months

  13. Change in serum TNF alpha

    serum concentration

    Measured: baseline and 6 months

  14. Change in serum uric acid

    serum concentration

    Measured: baseline and 6 months

  15. Change in MRI features of NASH

    serum concentration

    Measured: baseline and 6 months

Timeline

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

  1. First posted16 Nov 2016 (estimated)
  2. Study startNov 2016
  3. Primary completionNov 2018 (estimated)
  4. Study completionNov 2018 (estimated)

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 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02964715
Sponsor's protocol ID
ERF-4
Status last verified
May 2017
First submitted
30 Oct 2016
Last updated
31 May 2017
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016 Mar 17;374(11):1094. doi: 10.1056/NEJMc1600827. No abstract available.

    PubMed 26981940

  • Ferrannini E, Mark M, Mayoux E. CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis. Diabetes Care. 2016 Jul;39(7):1108-14. doi: 10.2337/dc16-0330.

    PubMed 27289126

  • Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol. 2013 Sep 5;715(1-3):246-55. doi: 10.1016/j.ejphar.2013.05.014. Epub 2013 May 23.

    PubMed 23707905

  • Hazlehurst JM, Woods C, Marjot T, Cobbold JF, Tomlinson JW. Non-alcoholic fatty liver disease and diabetes. Metabolism. 2016 Aug;65(8):1096-108. doi: 10.1016/j.metabol.2016.01.001. Epub 2016 Jan 11.

    PubMed 26856933

  • Ballestri S, Nascimbeni F, Romagnoli D, Lonardo A. The independent predictors of non-alcoholic steatohepatitis and its individual histological features.: Insulin resistance, serum uric acid, metabolic syndrome, alanine aminotransferase and serum total cholesterol are a clue to pathogenesis and candidate targets for treatment. Hepatol Res. 2016 Oct;46(11):1074-1087. doi: 10.1111/hepr.12656. Epub 2016 Mar 30.

    PubMed 26785389

  • Jojima T, Tomotsune T, Iijima T, Akimoto K, Suzuki K, Aso Y. Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes. Diabetol Metab Syndr. 2016 Jul 26;8:45. doi: 10.1186/s13098-016-0169-x. eCollection 2016.

    PubMed 27462372

  • Alisi A, Ceccarelli S, Panera N, Prono F, Petrini S, De Stefanis C, Pezzullo M, Tozzi A, Villani A, Bedogni G, Nobili V. Association between Serum Atypical Fibroblast Growth Factors 21 and 19 and Pediatric Nonalcoholic Fatty Liver Disease. PLoS One. 2013 Jun 26;8(6):e67160. doi: 10.1371/journal.pone.0067160. Print 2013.

    PubMed 23840612

  • Dushay JR, Toschi E, Mitten EK, Fisher FM, Herman MA, Maratos-Flier E. Fructose ingestion acutely stimulates circulating FGF21 levels in humans. Mol Metab. 2014 Oct 8;4(1):51-7. doi: 10.1016/j.molmet.2014.09.008. eCollection 2015 Jan.

    PubMed 25685689

  • Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21. doi: 10.1002/hep.20701.

    PubMed 15915461

  • Vanni E, Bugianesi E, Kotronen A, De Minicis S, Yki-Jarvinen H, Svegliati-Baroni G. From the metabolic syndrome to NAFLD or vice versa? Dig Liver Dis. 2010 May;42(5):320-30. doi: 10.1016/j.dld.2010.01.016. Epub 2010 Mar 6.

    PubMed 20207596

  • Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK. Empagliflozin for the Treatment of Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus. Dig Dis Sci. 2020 Feb;65(2):623-631. doi: 10.1007/s10620-019-5477-1. Epub 2019 Jan 25.

    PubMed 30684076

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Empagliflozin in people with Type2 Diabetes and NAFLD, run by University of Malaya at 1 site in Malaysia.

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 5 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 31 May 2017. 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 Malaysia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Shireene R Vethakkan, MD (0162093355, shireene.vethakkan@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in histological Grade as evaluated with Non-alcoholic Steatohepatitis Clinical Research Network Scoring System (time frame: baseline, 6 months). The study lists 2 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 NCT02964715, which also lists 11 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 31 May 2017.

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