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Dapagliflozin on Hyperlipidemia and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study) (DAPHNIS)

Primary Purpose

Diabetes Mellitus, Type 2

Status
Unknown status
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Dapagliflozin
Sponsored by
Osaka University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring sodium-glucose cotransporter 2 inhibitor, Diabetes Mellitus, Type 2, dyslipidemia, remnants, apolipoprotein B-48

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female subjects with type 2 diabetes mellitus of from 20 to 65 years of age.
  • Patients who have not achieve the clinical target of the glycemic control (less than 7.0% in HbA1c).
  • Patients who received the diet therapy, the exercise therapy or the following anti-diabetic drugs in addition to the diet and/or exercise therapy (up to two drugs) with dosage stable for 8 weeks prior to entry.
  • Sulfonylurea (Glymepiride 2mg/day or less, Glibenclamide 1.25mg/day or less, Gliclazide 40mg/day or less)
  • Thiazolidine (Actos)
  • Biguanide (Metformin, Buformin)
  • alpha-glucosidase inhibitor (Voglibose, Miglitol, Acarbose)
  • DPP4 inhibitors (Sitagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Saxagliptin)
  • Informed consent to participate in the study prior to any study procedures.

Exclusion Criteria:

  • Type 1 diabetes mellitus
  • Moderate or severe renal dysfunction (eGFR<45 ml/min/1.73m2 or hemodialysis)
  • Severe hepatic insufficiency (AST and/or ALT >3x upper limit of normal)
  • Adrenal insufficiency or pituitary gland dysfunction
  • Malnourishment, starvation, irregular dietary intake, poor dietary intake, debilitating condition or a severe muscle movement
  • Volume depleted patients; concomitant medication such as loop diuretics.
  • Excessive alcohol intake (>60g daily)
  • SGLT2 inhibitors such as dapagliflozin are already administered
  • Contraindication with dapagliflozin
  • Start a new medication of statins, fibrates, ezetimibe or probucol within a month
  • Females who are likely to be pregnant, during pregnancy or lactating
  • Participants in other clinical trials
  • Inability to communicate and comply with all study requirements.

Sites / Locations

  • Sousei Hospital
  • Osaka Central Hospital
  • Osaka University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dapagliflozin

Arm Description

Diabetic patients who met the inclusion/exclusion criteria. Dapagliflozin is orally administered for 8 weeks in the dose of 5mg per day if there is no serious event included in termination criteria. If the effect for improving diabetes is insufficient, it is allowed to raise its dose up to 10mg/day.

Outcomes

Primary Outcome Measures

Changes in fasting lipoprotein profiles
Changes in fasting lipoprotein profiles including concentrations of apoA-1, apoA-2, apoB, apoB-48, apoC-2, apoC-3, apoE, RemL-C, free-fatty acids profile, LPL protein mass and lipoprotein profile assessed by the HPLC at four and eight weeks after the administration of dapagliflozin

Secondary Outcome Measures

Changes in fasting lipid profiles
Changes in fasting lipid profiles including concentrations of triglyceride(TG), total cholesterol(TC), HDL-cholesterol (HDL-C) and LDL-C at four and eight weeks after the administration of dapagliflozin
Changes in fasting blood glucose and HbA1c
Changes in fasting blood glucose and HbA1c at four and eight weeks after the administration of dapagliflozin
Changes in insulin and adiponectin
Changes in other clinical profiles including concentrations of insulin and adiponectin
Frequency of adverse side effects
Frequency of adverse side effects at four and eight weeks after the administration of dapagliflozin
Changes in biomarkers for renal and hepatic function
Changes in biomarkers for renal and hepatic function at four and eight weeks after the administration of dapagliflozin.

Full Information

First Posted
August 11, 2015
Last Updated
August 27, 2018
Sponsor
Osaka University
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1. Study Identification

Unique Protocol Identification Number
NCT02577159
Brief Title
Dapagliflozin on Hyperlipidemia and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study)
Acronym
DAPHNIS
Official Title
Effects of Dapagliflozin on Hyperlipidemia, Glycemic Control and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Unknown status
Study Start Date
July 1, 2015 (undefined)
Primary Completion Date
December 31, 2017 (Actual)
Study Completion Date
August 31, 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Osaka University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators will investigate whether dapagliflozin (FORXIGA) might improve lipoprotein metabolism as well as hyperglycemia in Japanese patients with type II diabetes mellitus whose HbA1c levels are less than 7.0% (from 20 to 65 years of age). The investigators will examine changes of fasting lipoprotein profile including TG, TC, HDL-C, apoB-48 and RemL-C before and after the 8 weeks administration of dapagliflozin.
Detailed Description
In this study, the investigators will investigate whether dapagliflozin (FORXIGA) might improve lipoprotein metabolism as well as hyperglycemia in Japanese patients with type II diabetes mellitus. Primary Objective is to examine changes of fasting lipoprotein profile by the administration of dapagliflozin; Concentrations of apoB-48 and RemL-C. Secondary Objectives are; to examine changes of fasting glucose and HbA1c (NGSP) level by the administration of dapagliflozin, to examine changes of fasting lipid profile by the administration of dapagliflozin; Concentrations of TG, TC, HDL-C and LDL-C, to examine changes of fractions of free fatty acids, protein mass of LPL, and lipoprotein profile assessed by the HPLC by the administration of dapagliflozin, to examine changes of biomarkers for renal and hepatic function by the administration of dapagliflozin, and to examine the frequency of adverse effects by the administration of dapagliflozin. This study is open-label study and contains patients who are diabetes mellitus of from 20 to 65 years of age and their Patients who have not achieve the clinical target of the glycemic control (less than 7.0% in HbA1c).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
sodium-glucose cotransporter 2 inhibitor, Diabetes Mellitus, Type 2, dyslipidemia, remnants, apolipoprotein B-48

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dapagliflozin
Arm Type
Experimental
Arm Description
Diabetic patients who met the inclusion/exclusion criteria. Dapagliflozin is orally administered for 8 weeks in the dose of 5mg per day if there is no serious event included in termination criteria. If the effect for improving diabetes is insufficient, it is allowed to raise its dose up to 10mg/day.
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Other Intervention Name(s)
conventional treatment
Intervention Description
Dapagliflozin is orally administered for 8 weeks in the dose of 5mg per day by adding the conventional treatment if there is no serious event included in termination criteria. If the effect for improving diabetes is insufficient, it is allowed to raise its dose up to 10mg/day.
Primary Outcome Measure Information:
Title
Changes in fasting lipoprotein profiles
Description
Changes in fasting lipoprotein profiles including concentrations of apoA-1, apoA-2, apoB, apoB-48, apoC-2, apoC-3, apoE, RemL-C, free-fatty acids profile, LPL protein mass and lipoprotein profile assessed by the HPLC at four and eight weeks after the administration of dapagliflozin
Time Frame
at four and eight weeks after the administration of dapagliflozin
Secondary Outcome Measure Information:
Title
Changes in fasting lipid profiles
Description
Changes in fasting lipid profiles including concentrations of triglyceride(TG), total cholesterol(TC), HDL-cholesterol (HDL-C) and LDL-C at four and eight weeks after the administration of dapagliflozin
Time Frame
at four and eight weeks after the administration of dapagliflozin
Title
Changes in fasting blood glucose and HbA1c
Description
Changes in fasting blood glucose and HbA1c at four and eight weeks after the administration of dapagliflozin
Time Frame
at four and eight weeks after the administration of dapagliflozin
Title
Changes in insulin and adiponectin
Description
Changes in other clinical profiles including concentrations of insulin and adiponectin
Time Frame
at four and eight weeks after the administration of dapagliflozin
Title
Frequency of adverse side effects
Description
Frequency of adverse side effects at four and eight weeks after the administration of dapagliflozin
Time Frame
at four and eight weeks after the administration of dapagliflozin
Title
Changes in biomarkers for renal and hepatic function
Description
Changes in biomarkers for renal and hepatic function at four and eight weeks after the administration of dapagliflozin.
Time Frame
four and eight weeks after the administration of dapagliflozin.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects with type 2 diabetes mellitus of from 20 to 65 years of age. Patients who have not achieve the clinical target of the glycemic control (less than 7.0% in HbA1c). Patients who received the diet therapy, the exercise therapy or the following anti-diabetic drugs in addition to the diet and/or exercise therapy (up to two drugs) with dosage stable for 8 weeks prior to entry. Sulfonylurea (Glymepiride 2mg/day or less, Glibenclamide 1.25mg/day or less, Gliclazide 40mg/day or less) Thiazolidine (Actos) Biguanide (Metformin, Buformin) alpha-glucosidase inhibitor (Voglibose, Miglitol, Acarbose) DPP4 inhibitors (Sitagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Saxagliptin) Informed consent to participate in the study prior to any study procedures. Exclusion Criteria: Type 1 diabetes mellitus Moderate or severe renal dysfunction (eGFR<45 ml/min/1.73m2 or hemodialysis) Severe hepatic insufficiency (AST and/or ALT >3x upper limit of normal) Adrenal insufficiency or pituitary gland dysfunction Malnourishment, starvation, irregular dietary intake, poor dietary intake, debilitating condition or a severe muscle movement Volume depleted patients; concomitant medication such as loop diuretics. Excessive alcohol intake (>60g daily) SGLT2 inhibitors such as dapagliflozin are already administered Contraindication with dapagliflozin Start a new medication of statins, fibrates, ezetimibe or probucol within a month Females who are likely to be pregnant, during pregnancy or lactating Participants in other clinical trials Inability to communicate and comply with all study requirements.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shizuya Yamashita, MD, PhD
Organizational Affiliation
Osaka University Graduate School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sousei Hospital
City
Kadoma
State/Province
Osaka
ZIP/Postal Code
5710025
Country
Japan
Facility Name
Osaka Central Hospital
City
Osaka city
State/Province
Osaka
ZIP/Postal Code
5300001
Country
Japan
Facility Name
Osaka University Hospital
City
Suita
State/Province
Osaka
ZIP/Postal Code
5650871
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
21958700
Citation
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Results Reference
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21946533
Citation
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Results Reference
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PubMed Identifier
24882621
Citation
Okubo M, Hanada H, Matsui M, Hidaka Y, Masuda D, Sakata Y, Yamashita S. Serum apolipoprotein B-48 concentration is associated with a reduced estimated glomerular filtration rate and increased proteinuria. J Atheroscler Thromb. 2014;21(9):974-82. doi: 10.5551/jat.23309. Epub 2014 Jun 2.
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Citation
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Dapagliflozin on Hyperlipidemia and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study)

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