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SGLT2 Inhibitor Versus Sulfonylurea on Type 2 Diabetes With NAFLD

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ClinicalTrials.gov Identifier: NCT02649465
Recruitment Status : Recruiting
First Posted : January 7, 2016
Last Update Posted : January 7, 2016
Sponsor:
Collaborator:
Kowa Company, Ltd.
Information provided by (Responsible Party):
Toshinari Takamura, Kanazawa University

Tracking Information
First Submitted Date  ICMJE January 5, 2016
First Posted Date  ICMJE January 7, 2016
Last Update Posted Date January 7, 2016
Study Start Date  ICMJE January 2016
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2016)
The improvement in histologic features of NAFLD [ Time Frame: 48 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2016)
  • Change from baseline in liver enzymes [ Time Frame: 48 weeks ]
  • Change from baseline in body composition [ Time Frame: 48 weeks ]
  • Change from baseline in fasting plasma glucose level and glucose metabolism assessed with arginine tolerance test [ Time Frame: 48 weeks ]
  • Changes from baseline in organ-specific insulin sensitivity and glucagon response during a euglycemic hyperinsulinemic clamp study [ Time Frame: 48 weeks ]
  • Change from baseline in lipid profile [ Time Frame: 48 weeks ]
  • Change from baseline in renal function and electrolyte balances [ Time Frame: 48 weeks ]
  • Change from baseline in oxidative stress [ Time Frame: 48 weeks ]
  • Change from baseline in cytokine (TNF-alpha, leptin, adiponectin) levels [ Time Frame: 48 weeks ]
  • Change from baseline in hepatokine (Selenoprotein P, LECT2) levels [ Time Frame: 48 weeks ]
  • Change from baseline in organ-specific fat accumulation [ Time Frame: 48 weeks ]
  • Change from baseline in oxidative and non-oxidative glucose disposal [ Time Frame: 48 weeks ]
  • Change from baseline in respiratory quotients [ Time Frame: 48 weeks ]
  • Change from baseline in energy expenditure [ Time Frame: 48 weeks ]
  • Change from baseline in autonomic nerve function. [ Time Frame: 48 weeks ]
  • Changes from baseline in minerals and bone metabolism [ Time Frame: 48 weeks ]
  • Changes from baseline in endothelial functions [ Time Frame: 48 weeks ]
  • Changes from baseline in fatty acids profiles [ Time Frame: 48 weeks ]
  • 19. Factors associated with the changes in autonomic nerve function, organ-specific fat accumulation, and glucagon response. [ Time Frame: 48 weeks ]
  • Changes from baseline in gene expression profiles in the liver and blood cells [ Time Frame: 48 weeks ]
  • Changes from baseline in microRNAs and exosome contents [ Time Frame: 48 weeks ]
  • Epigenomic changes from baseline in genes of the liver and blood cells [ Time Frame: 48 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SGLT2 Inhibitor Versus Sulfonylurea on Type 2 Diabetes With NAFLD
Official Title  ICMJE Pleiotropic Effects and Safety of Sodium Glucose Co-transporter 2 Inhibitor Versus Sulfonylurea in Patients With Type 2 Diabetes and Non-alcoholic Fatty Liver
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?
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-alcoholic Fatty Liver Disease
Intervention  ICMJE
  • Drug: Tofogliflozin
    The group receiving Tofogliflozin (at a dose of 20mg once daily) for 48 weeks
    Other Name: DEBERZA
  • 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.
Study Arms  ICMJE
  • Active Comparator: SGLT2 inhibitor
    N=20 SGLT2 inhibitor dosage (Tofogliflozin): a dose of 20mg once daily for 48 weeks.
    Intervention: Drug: Tofogliflozin
  • Active Comparator: Sulfonylurea
    N=20 Sulfonylurea (Glimepiride): an initial dose of 0.5 mg once daily for 48 weeks.
    Intervention: Drug: Glimepiride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 5, 2016)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toshinari Takamura, MD,PhD +81-76-265-2234 ttakamura@m-kanazawa.jp
Contact: Yumie Takeshita, MD,PhD +81-76-265-2234 takeshita@m-kanazawa.jp
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02649465
Other Study ID Numbers  ICMJE 2015-033
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Toshinari Takamura, Kanazawa University
Study Sponsor  ICMJE Kanazawa University
Collaborators  ICMJE Kowa Company, Ltd.
Investigators  ICMJE
Study Chair: Toshinari Takamura, MD,PhD Japan, Department of Disease Control and Homeostasis, Kanazawa university hospital
PRS Account Kanazawa University
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP