UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Dapagliflozin effectiveness on the vascular endothelial function and glycemic control in T2D with moderately inadequate glycemic control
Title of the study (Brief title)	Dapagliflozin effectiveness on the vascular endothelial function and glycemic control (DEFENCE study)
Region	Japan

Condition
Condition	Type 2 diabetes
Classification by specialty	Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	This study attempts to reveal the positive effects of dapagliflozin on body weight, blood pressure, lipid metabolism, glycemic levels and endothelial function in Japanese T2D patients with moderately inadequate glycemic control including elderly, by using FMD and CAVI values to compare with metformin.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Change in FMD volume from baseline to the 16-week observation point
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -but assessor(s) are blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Dapagliflozin as add-on medication group: Patients enrolled in this group orally take dapagliflozin 5mg once per day in addition to other medications during the 16-week period.
Interventions/Control_2	Increase metformin dosage group: Patients enrolled in this group change their metformin dose from 750mg up to 1500mg, and orally take it in 2 or 3 times per day during the 16-week period.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	75 years-old >
Gender	Male and Female
Key inclusion criteria	Patients who meet all of the following criteria are included in this study. 1. In addition to a diet and exercise, type 2 diabetes patients who have been treating diabetes a) for more than 12 weeks using 750mg of metformin, or b) with one type of oral hypoglycemic agents* in addition to 750mg of metformin *In the case of SU users, glimepiride (2 mg or less than it) or glimicron (40 mg or less than it) are allowed 2. HbA1c (NGSP values) 6.0% or higher and under 8.0% 3. Males or females aged 20 to 74 4. Patients who can closely follow the medication compliance 5. Patients who can provided written consent to participate in the clinical study
Key exclusion criteria	Patients who fall into any of the following criteria are excluded from participating in the study. 1. Type 1 diabetes or secondary diabetes 2. Had used SGLT2 inhibitors, GLP-1 agonists, or insulin 12 weeks before providing their consent 3. Had used a dose of metformin exceeding 750mg per day 12 weeks before providing their consent 4. Had started taking angiotensin-converting enzyme inhibitor (ACE inhibitor), angiotensin II receptor antagonist (ARB), HMG-CoA reductase inhibitor (statin), or antiplatelet drugs, or had their medication dose changed (including reducing the dose) 12 weeks before providing their consent 5. Patients who have a severe infection, have had or are about to have surgery, or are suffering from a serious trauma 6. With a medical history of myocardial infarction, angina, stroke or cerebral infarction 7. With atrial (chronic) fibrillation, frequent supraventricular or ventricular ectopy 8. With a moderate or severe level of cardiac insufficiency (patients with class III or more as classified by the NYHA/New York Heart Association) 9. Ankle Brachial Pressure Index (ABI)< 0.9 10. Serious liver or renal functional failure (serum creatinine 1.3mg/dL or greater, or eGFR< 45mL/min/1.73 square meters) 11. Unstable blood pressure or lipid abnormalities within 12 weeks before providing their consent 12. Addicted to alcohol or drugs 13. Patients who are pregnant or breastfeeding, or who may be, or plan to be, pregnant 14. Dehydrated (abnormal test results of hematocrit and BUN values, and complaint of symptoms of dehydration) 15. Using diuretics 16. Urinary tract or genital infections within 12 weeks before providing their consent 17. With a past history of hypersensitivity to the study drug 18. At risks of ketoacidosis, diabetic coma or precoma 19. Other conditions considered to be unsuitable by the attending physician
Target sample size	80

Research contact person
Name of lead principal investigator	Prof. Takahisa Hirose
Organization	Toho University Omori Medical Center
Division name	Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine
Address	6-11-1 Omori Nishi, Ota-ku, Tokyo
TEL	03-3762-4151
Email	takahisa.hirose@med.toho-u.ac.jp

Public contact
Name of contact person	Hiroki Takayama
Organization	Soiken Inc.
Division name	Clinical Study Support Division
Address	NBF Ogawamachi Building 4F, Kanda Ogawamachi 1-3-1, Chiyoda-ku, Tokyo 101-0052
TEL	03-3295-1350
Homepage URL
Email	takayama@soiken.com

Sponsor
Institute	Japan Society for Patient Report Outcome
Institute
Department

Funding Source
Organization	AstraZeneca K.K. Ono Pharmaceutical Co., Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2015 Year 08 Month 21 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 08 Month 14 Day
Anticipated trial start date	2015 Year 10 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 08 Month 21 Day
Last modified on	2018 Year 11 Month 22 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021695