UMIN-CTR Clinical Trial

Public title

Exploring Mechanistic Study: Potential of Luseogliflozin on Restoration of Cardiomyocyte Energy Metabolism in Diabetic Patients with Heart Failure

Acronym

Exploring Mechanistic Study: Potential of Luseogliflozin on Restoration of Cardiomyocyte Energy Metabolism in Diabetic Patients with Heart Failure (EXPLORE-HF)

Scientific Title

Exploring Mechanistic Study: Potential of Luseogliflozin on Restoration of Cardiomyocyte Energy Metabolism in Diabetic Patients with Heart Failure

Scientific Title:Acronym

Exploring Mechanistic Study: Potential of Luseogliflozin on Restoration of Cardiomyocyte Energy Metabolism in Diabetic Patients with Heart Failure (EXPLORE-HF)

Region

Japan

Condition

Type2 Diabetes

Classification by specialty

Cardiology

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Targeting type 2 diabetes patients, the standard treatment of diabetes mellitus (no use of sodium glucose transporter 2 (SGLT2) inhibitors nor insulin injection) and a SGLT2 inhibitor treatment will be compared to discuss the mechanism of the drug to restore cardiomyocyte energy metabolism in heart failure in terms of keton metabolism, along with blood test and imaging test data.

Basic objectives2

Others

Basic objectives -Others

Exploratory study of Luseogliflozin, one of SGLT2 inhibitors, for its mechanism to restore cardiomyocyte energy metabolism.

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Change in the quantity and rate of keton absorbed by cardiac muscles in the second week of treatment.

Key secondary outcomes

1) Improvement in cardiac function in the second week and 6th month of treatment:brain natriuretic peptide (BNP), left ventricular diastolic performance (E/e'), and ejection fraction (EF).

2)Change in Hemoglobin A1c(HbA1c) and blood glucose level from the base line (zero week of treatment).

3)Change in BNP (and N-terminal pro-brain natriuretic peptide(NT-proBNP)from the base line (zero week of treatment).

4)Echocardiographic evaluation:E/e',LV mass index, EF, LA volume index.

5)Change in glycometabolism and fatty acid metabolism ove the two weeks of treatment.

6)Change in keton concentration over the two weeks of treatment and its relation to ALDH2 gene polymorphism.

7)Change in vascular endothelial function over the two weeks of treatment.

8)Hemodynamic status by right heart catheter over the two weeks of treatment.

9)Change in troponin T level over the two weeks of treatment.

10)Change in holter electrocardiogram over the two weeks of treatment.

11)Change in renal function over the six months of treatment.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

No need to know

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

The standard treatment (no use of SGLT2 inhibitors nor insulin injection)will be continued and observed for the predefined items for six months at maximum.

Interventions/Control_2

2.5mg of Luseogliflozin will be given daily in the morning and observed for the predefined items for six months at maximum.

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

Not applicable

Age-upper limit

85

years-old

>=

Gender

Male and Female

Key inclusion criteria

Type 2 diabetes patients who fulfill the following conditions;
1)Signed informed consent to join the study.
2)HbA1c level on the day of the consent signature is no less than 6.0% and no more than 12.0%.
3)Up to the day of the signature, have a history of heart failure, and ecocardiography taken within one year shows EF of no more than 55% or E/e' of no less than 15, with or without atrial fibrillation (AF).
4)WIthin 8 weeks up to the day of the signature, BNP level is no less than 40pg/mL or NT-proBNP is no less than 150pg/mL.
5)Within 8 weeks up to the day of the signature, the severity of heart failure is judged II to III according to the categorization by New York Heart Association (NYHA).
6)Cardiac catheterization is required to evaluate cardiac function and coronary artery condition.

Key exclusion criteria

Any person who
1)Has type I diabetes.
2)Requires insulin for blood glucose control (including the conditions such as severe ketosis, diabetic coma or precoma, severe infectious disease, perioperative period, or severe trauma).
3)Had severe renal dysfunction (estimated glomerular filtration rate (eGFR) is less than 45mL/min/1.73m2 or dialysis is required).
4)Has severe hepatic dysfunciton.
5)Has a history of the following disorders within 12 weeks up to the day of the signature;acute coronary syndromes, cerebrovascular disorder, myocarditis, pericarditis constrictiva, or severe valvular disorder.
6)Has heart failure of severity IV according to the categorization by New York Heart Association (NYHA).
7)Body mass index (BMI) is less than 18.5kg/m2 or at malnutrition or starvation state.
8)Has a history of intolerance to the target drug.
9)Is pregnant, breast-feeding, or likely pregnant.
10)Is diagnosed of malignant tumor or so suspected.
11)Is a the age of 85 or older.
12)Is judged inappropriate for the study by the investigators.

Target sample size

80

Name of lead principal investigator

1st name	Yuji
Middle name
Last name	Mizuno

Organization

Medical Corporataion Juryo
Kumamoto Kinoh Hospital

Division name

Cardiovascular internal medicine

Zip code

8608518

Address

6-8-1 Yamamuro Kita-ku, Kumamoto

TEL

096-345-8111ext.3057

Email

mizuno@juryo.or.jp

Name of contact person

1st name	Yuji
Middle name
Last name	Mizuno

Organization

Medical Corporataion Juryo Kumamoto Kinoh Hospital

Division name

Cardiovascular internal medicine

Zip code

8608518

Address

6-8-1 Yamamuro Kita-ku, Kumamoto

TEL

096-345-8111ext.3057

Homepage URL

Email

mizuno@juryo.or.jp

Institute

Cardiovascular internal medicine

Medical Corporataion Juryo
Kumamoto Kinoh Hospital

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Kumamoto Kinoh Hospital

Address

6-8-1 Yamamuro Kita-ku, Kumamoto

Tel

0963458111

Email

medlab@juryo.or.jp

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

2019

Year

01

Month

04

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

Open public recruiting

Date of protocol fixation

2018

Year

11

Month

13

Day

Date of IRB

2018

Year

11

Month

22

Day

Anticipated trial start date

2019

Year

01

Month

04

Day

Last follow-up date

2024

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

12

Month

13

Day

Last modified on

2020

Year

07

Month

03

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039844