UMIN-CTR Clinical Trial

Public title

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

Acronym

PRIME-V Study

Scientific Title

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

Scientific Title:Acronym

PRIME-V Study

Region

Japan

Condition

Type 2 diabetes mellitus

Classification by specialty

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Koutaro Yokote

Organization

Chiba University

Division name

Department of Medicine, Division of Metabolism and Endocrinology

Zip code

Address

1-8-1 Inohana, Chuo-ku, Chiba

TEL

043-226-2089

Email

kyokote@faculty.chiba-u.jp

Name of contact person

1st name
Middle name
Last name	Kou Ishikawa

Organization

Chiba University

Division name

Department of Medicine, Division of Metabolism and Endocrinology

Zip code

Address

1-8-1 Inohana, Chuo-ku, Chiba

TEL

043-226-2089

Homepage URL

Email

ishikawako@chiba-u.jp

Institute

Chiba University Hospital

Institute

Department

Personal name

Organization

Astellas Pharma Inc.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2014

Year

09

Month

21

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2014

Year

09

Month

21

Day

Date of IRB

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

Other related information

Registered date

2014

Year

09

Month

16

Day

Last modified on

2017

Year

05

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016861