UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Prospective and randomized controlled study on the efficacy and safety of ipragliflozin and metformin to visceral fat reduction for the patients being treated with DPP-4 inhibitors for poor glycemic controlled type-2 diabetes
Title of the study (Brief title)	PRIME-V Study
Region	Japan

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

Objectives
Narrative objectives1	Iplagliflozin, a sodium-dependent glucose transporter-2 (SGLT-2) inhibitor, is quite different from existing diabetic medications in that it reduces the body's plasma glucose level by promoting the excretion of glucose through urine. Moreover, it reduces not only plasma glucose level but also body weight; however, it is not clear whether it has an effect on (visceral and subcutaneous) fat, muscle, or bone. Recently in Japan, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently becoming the first choice for treating patients with type-2 diabetes. They are effective for Japanese patients with type 2 diabetes because they tend to have low insulin secretion. In some cases, however, poor glycemic and body weight control issues persist despite treatment with DPP-4 inhibitors. Therefore, we aim to study if iplagiliflozin and/or metformin reduce visceral fat after 6 months in type 2 diabetes patients with poor glycemic control and a BMI of over 22 kg/m2 via randomized control trial. We will carry out measurements of visceral fat with CT measurements at the middle of the 4th lumber vertebra level. We will also evaluate the drug's effects on other metabolic parameters, such as body weight, BMI, plasma glucose level, blood pressure, cholesterol level, waist circumference, bone density, muscle strength, muscle mass, and basal metabolism as secondary endpoints. The reduction of visceral fat is expected to lead to the reduction of metabolic syndrome and the prevention of atherosclerotic disease. On the other hand, there is concern that SGLT-2 inhibitors may cause a loss of muscle and bone mass and lead to osteoporosis and a decline in physical function. We aim find evidence of the safety and efficacy of iplagiliflozin on visceral fat and plasma glucose level reduction.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	The change rate of the visceral fat area by CT after 24 weeks therapy in the two groups
Key secondary outcomes	(1) HbA1c (NGSP) (2) Body weight, BMI (3) Waist circumference (4) ALP (BAP), TRACP5b (5) Muscle strength (6) Fasting plasma glucose level, HOMA-b, HOMA-R (7) Cholesterol level (TC, LDL-C, fasting TG, HDL-C) (8) Blood pressure (9) Adipocytokine (adiponectin), inflammatory marker (hs-CRP) (10) Subctaneus fat area, total fat area (11) Respiratory quotient, basal metabolism, whole body DXA, eating behavior questionnaire, calories and glucose amount (12) The change rate of the abdominal muscle area by CT after 24 weeks therapy in the two groups (13) The change rate of the bone density in the fourth lumbar vertebra by CT after 24 weeks therapy in the two groups

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	Ipragliflozin 50mg
Interventions/Control_2	Metformin 1000mg (Up to 1500mg)
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	(1) Type 2 Diabetes (Over 20 and under 75 years of age) (2) Patients who have been unable to adequately control their blood sugar levels despite being administered 50mg of DPP-4 inhibitor sitagliptin for over 12 weeks. (3) HbA1c (NGSP) over 7.0%/under 10.0% (4) BMI over 22kg/m2 (5) eGFR over 50 mL/ min/1.73m2 (6) Patients who have received adequate explanation of the contents of the trial and given their written consent.
Key exclusion criteria	(1) Type 1 Diabetes (2) Patients who have experienced metabolic acidosis, diabetic coma and/or pre-coma within six months prior to providing consent (3) Serious infections requiring insulin treatment, prior/upcoming surgeries, and/or severe injuries. (4) Patients with considerable loss of kidney function (creatine blood level of over 1.3mg/dL in men, and over 1.2mg/dL in women) and/or undergoing dialysis (including peritoneal dialysis) (5) Serious liver damage (6) History of stroke, myocardial infarction, heart failure as well as other severe cardiovascular complications requiring hospitalization (7) Patient is taking oral hypoglycemic agents other than DPP-4 inhibitors at the start of the trial. (8) Women who are pregnant or nursing, or could become pregnant (9) History of chemical sensitivity to DPP-4 inhibitors, SGLT2 inhibitors, and/or metformin (10) Suffering or at risk from urinary tract infection and/or dehydration (11) Tested positive for Ketone bodies (12) History of lactic acidosis (13) Excessive alcohol consumption (14) History of osteoporosis (15) Patients who have undergone a CT scan within 3 months prior to providing written consent (16) Determined to be ineligible by the physician in charge for any other reason
Target sample size	106

Research contact person
Name of lead principal investigator	Koutaro Yokote
Organization	Chiba University
Division name	Department of Medicine, Division of Metabolism and Endocrinology
Address	1-8-1 Inohana, Chuo-ku, Chiba
TEL	043-226-2089
Email	kyokote@faculty.chiba-u.jp

Public contact
Name of contact person	Kou Ishikawa
Organization	Chiba University
Division name	Department of Medicine, Division of Metabolism and Endocrinology
Address	1-8-1 Inohana, Chuo-ku, Chiba
TEL	043-226-2089
Homepage URL
Email	ishikawako@chiba-u.jp

Sponsor
Institute	Chiba University Hospital
Institute
Department

Funding Source
Organization	Astellas Pharma Inc.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

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	2014 Year 09 Month 21 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 09 Month 21 Day
Anticipated trial start date	2014 Year 09 Month 21 Day
Last follow-up date	2017 Year 05 Month 12 Day
Date of closure to data entry	2017 Year 07 Month 16 Day
Date trial data considered complete	2017 Year 07 Month 31 Day
Date analysis concluded	2017 Year 08 Month 31 Day

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

Management information
Registered date	2014 Year 09 Month 16 Day
Last modified on	2017 Year 05 Month 16 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016861