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

Sponsor
University of Malaya (Other)
Overall Status
Unknown status
CT.gov ID
NCT02964715
Collaborator
(none)
25
Enrollment
1
Location
1
Arm
24
Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

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
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 Design

Study Type:
Interventional
Anticipated Enrollment :
25 participants
Allocation:
N/A
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 :
Nov 1, 2016
Anticipated Primary Completion Date :
Nov 1, 2018
Anticipated Study Completion Date :
Nov 1, 2018

Arms and Interventions

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 Names:
  • Jardiance

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in histological Grade as evaluated with Non-alcoholic Steatohepatitis Clinical Research Network Scoring System [baseline, 6 months]

      liver biopsy

    2. Change in serum FGF 21 [baseline and 6 months]

      blood test

    Secondary Outcome Measures

    1. Change in fibroscan and elastography measure of liver stiffness [baseline and 6 months]

      imaging

    2. Change in Liver enzymes [baseline and 6 months]

      blood test - AST,ALT, gamma GT

    3. Change in steatosis [baseline and 6 months]

      histological

    4. Change in lobular inflammation [baseline and 6 months]

      histological

    5. Change in ballooning [baseline and 6 months]

      histological

    6. Change in fibrosis [baseline and 6 months]

      histological

    7. Change in metabolic outcome -HbA1c [baseline and 6 months]

      serum concentration

    8. Change in metabolic outcome - fasting NEFA [baseline and 6 months]

      serum concentration

    9. Change in metabolic outcome - fasting Tg [baseline and 6 months]

      serum concentration

    10. Change in serum FGF 19 [baseline and 6 months]

      serum concentration

    11. Change in serum adiponectin [baseline and 6 months]

      serum concentration

    12. Change in serum IL-6 [baseline and 6 months]

      serum concentration

    13. Change in serum TNF alpha [baseline and 6 months]

      serum concentration

    14. Change in serum uric acid [baseline and 6 months]

      serum concentration

    15. Change in MRI features of NASH [baseline and 6 months]

      serum concentration

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Malaya Kuala Lumpur Wilayah Persekutuan Malaysia

    Sponsors and Collaborators

    • University of Malaya

    Investigators

    • Principal Investigator: Shireene R Vethakkan, MD, University of Malaya

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Shireene Vethakkan, Associate Professor Dr., University of Malaya
    ClinicalTrials.gov Identifier:
    NCT02964715
    Other Study ID Numbers:
    • ERF-4
    First Posted:
    Nov 16, 2016
    Last Update Posted:
    May 31, 2017
    Last Verified:
    May 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Non-alcoholic Fatty Liver Disease
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Empagliflozin

    Study Results

    No Results Posted as of May 31, 2017