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SGLT2 Inhibitor Versus Sulfonylurea on Type 2 Diabetes With NAFLD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02649465
Recruitment Status : Unknown
Verified November 2015 by Toshinari Takamura, Kanazawa University.
Recruitment status was:  Recruiting
First Posted : January 7, 2016
Last Update Posted : January 7, 2016
Kowa Company, Ltd.
Information provided by (Responsible Party):
Toshinari Takamura, Kanazawa University

Brief Summary:

1. Objectives

  1. Which organ and how does SGLT2 inhibitor alter insulin sensitivity?
  2. How does SGLT2 inhibitor increase glucagon levels and hepatic glucose production?

Condition or disease Intervention/treatment Phase
Non-alcoholic Fatty Liver Disease Drug: Tofogliflozin Drug: Glimepiride Phase 4

Detailed Description:

2. Clinical hypothesis

  1. SGLT2 inhibitor ameliorates fatty liver and obesity.
  2. SGLT2 inhibitor stimulates sympathetic activity.
  3. SGLT2 inhibitor increases glucagon secretion.
  4. SGLT2 inhibitor enhances lipolysis and hepatic glucose production.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pleiotropic Effects and Safety of Sodium Glucose Co-transporter 2 Inhibitor Versus Sulfonylurea in Patients With Type 2 Diabetes and Non-alcoholic Fatty Liver
Study Start Date : January 2016
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Arm Intervention/treatment
Active Comparator: SGLT2 inhibitor
N=20 SGLT2 inhibitor dosage (Tofogliflozin): a dose of 20mg once daily for 48 weeks.
Drug: Tofogliflozin
The group receiving Tofogliflozin (at a dose of 20mg once daily) for 48 weeks
Other Name: DEBERZA

Active Comparator: Sulfonylurea
N=20 Sulfonylurea (Glimepiride): an initial dose of 0.5 mg once daily for 48 weeks.
Drug: Glimepiride
Sulfonylurea dosage (Glimepiride): dosing from 0.5 mg for initial 4 weeks. Then, if there is no adverse effect or no improvement of glucose metabolism, glimepiride is escalated to 6 mg once daily.

Primary Outcome Measures :
  1. The improvement in histologic features of NAFLD [ Time Frame: 48 weeks ]

Secondary Outcome Measures :
  1. Change from baseline in liver enzymes [ Time Frame: 48 weeks ]
  2. Change from baseline in body composition [ Time Frame: 48 weeks ]
  3. Change from baseline in fasting plasma glucose level and glucose metabolism assessed with arginine tolerance test [ Time Frame: 48 weeks ]
  4. Changes from baseline in organ-specific insulin sensitivity and glucagon response during a euglycemic hyperinsulinemic clamp study [ Time Frame: 48 weeks ]
  5. Change from baseline in lipid profile [ Time Frame: 48 weeks ]
  6. Change from baseline in renal function and electrolyte balances [ Time Frame: 48 weeks ]
  7. Change from baseline in oxidative stress [ Time Frame: 48 weeks ]
  8. Change from baseline in cytokine (TNF-alpha, leptin, adiponectin) levels [ Time Frame: 48 weeks ]
  9. Change from baseline in hepatokine (Selenoprotein P, LECT2) levels [ Time Frame: 48 weeks ]
  10. Change from baseline in organ-specific fat accumulation [ Time Frame: 48 weeks ]
  11. Change from baseline in oxidative and non-oxidative glucose disposal [ Time Frame: 48 weeks ]
  12. Change from baseline in respiratory quotients [ Time Frame: 48 weeks ]
  13. Change from baseline in energy expenditure [ Time Frame: 48 weeks ]
  14. Change from baseline in autonomic nerve function. [ Time Frame: 48 weeks ]
  15. Changes from baseline in minerals and bone metabolism [ Time Frame: 48 weeks ]
  16. Changes from baseline in endothelial functions [ Time Frame: 48 weeks ]
  17. Changes from baseline in fatty acids profiles [ Time Frame: 48 weeks ]
  18. 19. Factors associated with the changes in autonomic nerve function, organ-specific fat accumulation, and glucagon response. [ Time Frame: 48 weeks ]
  19. Changes from baseline in gene expression profiles in the liver and blood cells [ Time Frame: 48 weeks ]
  20. Changes from baseline in microRNAs and exosome contents [ Time Frame: 48 weeks ]
  21. Epigenomic changes from baseline in genes of the liver and blood cells [ Time Frame: 48 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. The biopsy consistent with the diagnosis of NAFLD
  2. Type 2 diabetes, HbA1c >=7.0%

Exclusion Criteria:

  1. Hepatic virus infections (hepatitis C virus RNA-PCR-positive, hepatitis B and C, cytomegalovirus and Epstein-Barr virus), autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis, haemochromatosis, alpha 1-antitrypsin deficiency, Wilson's disease, history of parenteral nutrition and use of drugs known to induce steatosis (e.g. valproate, amiodarone and prednisone) or hepatic injury caused by substance abuse and/or the current or past consumption of more than 20 g of alcohol daily
  2. Hypersensitivity to or contraindication of glimepiride and tofogliflozin
  3. None- type 2 diabetes
  4. Poorly controlled diabetes (states of hyperglycemic hyperosmolar syndrome and diabetic ketoacidosis)
  5. Repeated episodes of unexplained hypoglycemia, as defined by a FPG <60 mg/dl, with or without symptoms of hypoglycemia
  6. Concomitant infection or planned surgery
  7. Poorly controlled hypertension (systolic blood pressure >160 mmHg, or diastolic blood pressure >100 mmHg)
  8. Severe retinopathy
  9. Malignancy on an active therapeutic regimen or malignancy without complete remission or cure
  10. Severe health problems not suitable for the study
  11. Pregnant or lactating women
  12. Inability to participate in the study (psychiatric status or psychosocial status) as assessed by the investigators.

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 identifier (NCT number): NCT02649465

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Contact: Toshinari Takamura, MD,PhD +81-76-265-2234
Contact: Yumie Takeshita, MD,PhD +81-76-265-2234

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Department of Disease Control and Homeostasis, Kanazawa University Hospital Recruiting
Kanazawa, Ishikawa, Japan, 920-8641
Contact: Toshinari Takamura, MD, PhD    +81-76-265-2234   
Principal Investigator: Yumie Takeshita, MD, PhD         
Sponsors and Collaborators
Kanazawa University
Kowa Company, Ltd.
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Study Chair: Toshinari Takamura, MD,PhD Japan, Department of Disease Control and Homeostasis, Kanazawa university hospital
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Toshinari Takamura, Department of Disease Control and Homeostasis, Kanazawa University Identifier: NCT02649465    
Other Study ID Numbers: 2015-033
First Posted: January 7, 2016    Key Record Dates
Last Update Posted: January 7, 2016
Last Verified: November 2015
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Anti-Arrhythmia Agents
Hypoglycemic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action