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Trial record 43 of 187 for:    BI10773

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

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ClinicalTrials.gov Identifier: NCT02964715
Recruitment Status : Recruiting
First Posted : November 16, 2016
Last Update Posted : May 31, 2017
Sponsor:
Information provided by (Responsible Party):
Shireene Vethakkan, University of Malaya

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Type2 Diabetes NAFLD Drug: Empagliflozin Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: open label
Primary Purpose: Treatment
Official Title: The Effect of Empagliflozin on NAFLD in Asian Patients With Type 2 Diabetes
Study Start Date : November 2016
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2018


Arm Intervention/treatment
Experimental: Interventional arm
Patients with NAFLD and Type 2 Diabetes prescribed 25mg empagliflozin(JARDIANCE) daily for 6 months
Drug: Empagliflozin
25 mg daily for 6 months
Other Name: Jardiance




Primary Outcome Measures :
  1. Change in histological Grade as evaluated with Non-alcoholic Steatohepatitis Clinical Research Network Scoring System [ Time Frame: baseline, 6 months ]
    liver biopsy

  2. Change in serum FGF 21 [ Time Frame: baseline and 6 months ]
    blood test


Secondary Outcome Measures :
  1. Change in fibroscan and elastography measure of liver stiffness [ Time Frame: baseline and 6 months ]
    imaging

  2. Change in Liver enzymes [ Time Frame: baseline and 6 months ]
    blood test - AST,ALT, gamma GT

  3. Change in steatosis [ Time Frame: baseline and 6 months ]
    histological

  4. Change in lobular inflammation [ Time Frame: baseline and 6 months ]
    histological

  5. Change in ballooning [ Time Frame: baseline and 6 months ]
    histological

  6. Change in fibrosis [ Time Frame: baseline and 6 months ]
    histological

  7. Change in metabolic outcome -HbA1c [ Time Frame: baseline and 6 months ]
    serum concentration

  8. Change in metabolic outcome - fasting NEFA [ Time Frame: baseline and 6 months ]
    serum concentration

  9. Change in metabolic outcome - fasting Tg [ Time Frame: baseline and 6 months ]
    serum concentration

  10. Change in serum FGF 19 [ Time Frame: baseline and 6 months ]
    serum concentration

  11. Change in serum adiponectin [ Time Frame: baseline and 6 months ]
    serum concentration

  12. Change in serum IL-6 [ Time Frame: baseline and 6 months ]
    serum concentration

  13. Change in serum TNF alpha [ Time Frame: baseline and 6 months ]
    serum concentration

  14. Change in serum uric acid [ Time Frame: baseline and 6 months ]
    serum concentration

  15. Change in MRI features of NASH [ Time Frame: baseline and 6 months ]
    serum concentration



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02964715


Contacts
Contact: Shireene R Vethakkan, MD 0162093355 shireene.vethakkan@gmail.com
Contact: Wah K Chan, MRCP 0163655232 wahkheong2003@hotmail.com

Locations
Malaysia
University of Malaya Recruiting
Kuala Lumpur, Wilayah Persekutuan, Malaysia
Contact: Shireene R Vethakkan, MD    0162093355    shireene.vethakkan@gmail.com   
Sub-Investigator: Wah K Chan, MRCP         
Sponsors and Collaborators
University of Malaya
Investigators
Principal Investigator: Shireene R Vethakkan, MD University of Malaya

Publications:

Responsible Party: Shireene Vethakkan, Associate Professor Dr., University of Malaya
ClinicalTrials.gov Identifier: NCT02964715     History of Changes
Other Study ID Numbers: ERF-4
First Posted: November 16, 2016    Key Record Dates
Last Update Posted: May 31, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Empagliflozin
Diabetes Mellitus
Diabetes Mellitus, Type 2
Non-alcoholic Fatty Liver Disease
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Fatty Liver
Liver Diseases
Digestive System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs