UMIN-CTR Clinical Trial

Public title

A prospective Randomized study comparing the effects of Empagliflozin versus Sitagliptin on Intra hepatic lipid content and hepatic insulin resistance in type 2 diabetes patients / Resistance study

Acronym

A prospective Randomized study comparing the effects of Empagliflozin versus Sitagliptin on Intra hepatic lipid content and hepatic insulin resistance in type 2 diabetes patients / Resistance study

Scientific Title

A prospective Randomized study comparing the effects of Empagliflozin versus Sitagliptin on Intra hepatic lipid content and hepatic insulin resistance in type 2 diabetes patients / Resistance study

Scientific Title:Acronym

A prospective Randomized study comparing the effects of Empagliflozin versus Sitagliptin on Intra hepatic lipid content and hepatic insulin resistance in type 2 diabetes patients / Resistance study

Region

Japan

Condition

Type 2 Diabetes Mellitus

Classification by specialty

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Ectopic adiposity including liver intracellular lipid, reducing effects and hepatic insulin resistance improving effects observed in type 2 diabetic patients using SGLT2 (empagliflozin), are compared to that of patients using DPP-4 inhibitor (sitagliptin). Also, as the characteristics of patients showing treatment efficacy, patients' background information such as insulin resistance, lipid prevalence, life style, gene expression and antidiabetic medications related to treatment efficacy are planned to elucidate.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Evaluation of the following value changed from the baseline and the percent change:
* Amount of hepatic lipid accumulation (measured by MRI, Proton MRS)

Key secondary outcomes

Evaluation of the following values changed from the baseline and the percent change:
1. Liver insulin sensitivity (measured by the hyperinsulinemic-euglycemic clamp technique)
2. Muscle, adipose insulin sensitivity (measured by the hyperinsulinemic-euglycemic clamp technique)
3. Hepatic fibrosis index (Type IV collagen 7s, ferritin, PIIIP, hyaluronic acid)
4. Liver gluconeogenesis index (cortisol)
5. Epithelial cell apoptosis index (CK18 fragment)
6. Hepatokine (hepatic hormone ) index (FGF21, Fetuin A)
7.Other index related to liver (Hepatocyte growth factor, insulin-like growth factor 1/IGF-1)
8. Adipose amount (intraperitoneal adipose amount, subcutaneous fat amount) by CT scans
9. Body weight, whole-body adipose amount, fat removal quantity, bone and muscle mass by DEXA scans
10. Physical activity level
11. Scores of the questionnaires answered by patients

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

Group A: Administer empagliflozin

Patients in this empagliflozin group take empagliflozin 10 mg once a day orally before or after breakfast, and continue it for 12 weeks.

Interventions/Control_2

Group B: Administer sitagliptin

Patients begin with sitagliptin 50 mg a day, in principle, and increase the dose to 100 mg from their observation point of the 4th week, if it is possible. They also take sitagliptin orally once a day before or after breakfast, and continue it for 12 weeks.

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

Patients who meet all of the following criteria are included in this study.

1. Type 2 diabetic patients with HbA1c below 10% at the time of consenting

2. Female and male patients are 20 years old or older and younger than 75 years old

3. Patients who can take liver biopsy for the purpose of evaluation or diagnosis of non-alcohol fatty liver disease

4. Patients with BMI 22 kg/m2 or higher

5. Patients who can provide their written consent for participation of this study

Key exclusion criteria

Patients who fall into any of the following criteria are excluded from participating in the study.

1. Patients with type 1 diabetes or secondary diabetes

2. Patients with BMI lower than 22 kg/m2

3. Patients with moderate to severe renal function disease or at the final stage of renal failure (eGFR lower than 45 mL/min/1.73 m2)

4. Patients who had stroke or cerebral infarction within 12 weeks before giving their consent

5. Patients with any medical history of myocardial infarction, angina pectoris, or currently with atrial fibrillation

6. Patients with any infectious disease

7. Patients with malignancy (However, those who have completed treatment and/or show no redevelopment of malignancy, as well as manifest some degree of remission can be considered to be participants of this study)

8. Patients with connective tissue disease (However, those T2DM patients who have treated with prednisolone 5 mg or less and show stable conditions can be considered to be participants of this study)

9. Patients with hepatocirrhosis

10. Patients with viral or autoimmune, or drug-induced hepatic disorder

11. Patients who are alcoholic or excessive drinkers

12. Patients who are currently pregnant, possibly pregnant, or breast-feeding during the study

13. Patients have a medical history of hypersensitivity to the study drugs

14. Patients who are in the category that the study drugs are prohibited to use

15. Patients with Hb below 12 g/dl

16. Patients with other conditions that investigators/physicians think inappropriate to be in the study

Target sample size

44

Name of lead principal investigator

1st name
Middle name
Last name	Professor Takahisa Hirose, Instructor Naoki Kumashiro

Organization

Toho University Omori Medical Center

Division name

Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine

Zip code

Address

6-11-1 Omori Nishi, Ota-ku, Tokyo

TEL

03-3762-4151

Email

takahisa.hirose@med.toho-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Hiroki Takayama

Organization

Soiken Inc.

Division name

Clinical Study Support Division

Zip code

Address

NBF Ogawamachi Building 4F, 1-3-1 Ogawamachi, Kanda, Chiyoda-ku, Tokyo

TEL

03-3295-1350

Homepage URL

Email

takayama@soiken.com

Institute

Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University Omori Medical Center

Institute

Department

Personal name

Organization

Department of Internal Medicine (Omori), Toho University

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

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

2017

Year

03

Month

30

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

2017

Year

03

Month

13

Day

Date of IRB

2016

Year

12

Month

15

Day

Anticipated trial start date

2017

Year

04

Month

01

Day

Last follow-up date

2019

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

03

Month

30

Day

Last modified on

2023

Year

10

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030754