UMIN-CTR Clinical Trial

Basic information
Public title	Clinical Study for the Effect of Teneligliptin on the Progressive Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes Mellitus
Acronym	TOPLEVEL (Teneligliptin on the Progressive Left Ventricular Diastolic Dysfunction with Type 2 Diabetes Mellitus)
Scientific Title	Clinical Study for the Effect of Teneligliptin on the Progressive Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes Mellitus
Scientific Title:Acronym	TOPLEVEL (Teneligliptin on the Progressive Left Ventricular Diastolic Dysfunction with Type 2 Diabetes Mellitus)
Region	Japan

Condition
Condition	Type 2 Diabetes Mellitus
Classification by specialty	Cardiology Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To investigate whether teneligliptin, one of the Dipeptidyl Peptidase-4 inhibitors, 1) maintain left ventricular diastolic function in patient with type 2 diabetes mellitus showing normal left ventricular diastolic function or 2) improve the progression of left ventricular diastolic dysfunction in patient with type 2 diabetes mellitus showing reduced left ventricular diastolic function by comparing with anti-diabetic agents except for DPP-4 inhibitors in multicenter, randomized, open clinical trial
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase IV

Assessment
Primary outcomes	Change of the ratio of peak velocity of early transmitral diastolic filling by echocardiography (E) to early diastolic mitral annular velocity by tissue Doppler echocardiography (E/e') for 2 years from baseline
Key secondary outcomes	- Total number of all-cause death for 2 years from baseline - Total number of deaths by cardiovascular events for 2 years from baseline - Total number of all-cause hospitalization for 2 years from baseline - Total number of hospitalization by cardiovascular events for 2 years from baseline - Total number of hospitalization by progression of heart failure for 2 years from baseline - Total number of incidents for the addition or increase of the agents for heart failure by progression of heart failure for 2 years from baseline - Change of the ratio of peak velocity of early transmitral diastolic filling (E) to late diastolic filling due to atrial contraction (E/A) by echocardiography for 2 years from baseline - Change of the deceleration time (DT) by echocardiography for 2 years from baseline - Change of the left atrium volume (LAV) by echocardiography for 2 years from baseline - Change of the left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs) and fractional shortening (%FS) by echocardiography for 2 years from baseline - Change of the left ventricular mass index (LVMI) by echocardiography for 2 years from baseline - Change of NYHA functional class for 2 years from baseline - Change of plasma levels of NT-proBNP for 2 years from baseline

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -but assessor(s) are blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	4
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	The arm treated by Teneligliptin in the inhibition test Patients showing E/e' by echocardiography less than 8 at base line and assigned as Teneligliptin treatment by randomization
Interventions/Control_2	The arm treated by anti-diabetic agents except for DPP-4 inhibitors in the inhibition test Patients showing E/e' by echocardiography less than 8 at base line and assigned as anti-diabetic agents except for DPP-4 inhibitors treatment by randomization
Interventions/Control_3	The arm treated by Teneligliptin in the improvement test Patients showing E/e' by echocardiography more than 8 at base line and assigned as Teneligliptin treatment by randomization
Interventions/Control_4	The arm treated by Teneligliptin in the improvement test Patients showing E/e' by echocardiography more than 8 at base line and assigned as anti-diabetic agents except for DPP-4 inhibitors treatment by randomization
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	85 years-old >
Gender	Male and Female
Key inclusion criteria	1) Asian aged from 20 to 85 years old at baseline 2) Patients with type 2 diabetes mellitus and including either a) or b) criteria a)Patients necessary to start the treatment using anti-diabetic agent(s) or to change the anti-diabetic agent(s) b)Patients possible to change the anti-diabetic agent(s) 3) Patients with left ventricular ejection fraction more than 40% 4) Patients with written informed consent
Key exclusion criteria	- Patients with type 1 diabetes mellitus - Patients with slowly progressive type 1 diabetes mellitus positive for pancreatic islets related autoimmune antibody as GAD antibody or IA-2 antibody or ICA antibody - Patients with diabetes mellitus caused by evident genetic factors - Patients with diabetes mellitus caused by secondary factors as endocrine disease or liver disease - Patients with diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome - Patients with any severe infectious diseases or planed any surgical treatments or suffered any severe traumas - Patients with severe liver dysfunction - Patients with hypophyseoprivic or adrenal insufficiency - Patients under malnutrition or starved state or irregular caloric intake or calorie insufficiency or hyposthenia - Patients judged to be unsuitable for the study as they are planning to exercise intensively - Patients judged to be unsuitable for the study as they may drink excessively or abuse drugs - Patients with a prior history of ileus - Patients showing QT prolongation in the electrocardiogram - Patients with any past histories of heart failure showing NYHA classification grade more than 3 at baseline - Patients with any past histories of acute coronary syndrome or coronary intervention or cardiac surgery developed within 6 months - Patients with any surgical past histories of mitral valve replacement or mitral valve repair or severe calcification of mitral valve - Patients already treated with Teneligliptin - Patients who have already received DPP-4 inhibitors and are not able to change these drugs - Women with breast-feeding - Pregnant women or patients who have possibilities of pregnancy - Patients expected to live less than 3 years - Patients with any past histories of drug hypersensitivity against Teneligliptin - Patients already involved in any other interventional clinical trials or planned to be involved - Patients judged to be inappropriate for the study by the doctors in charge
Target sample size	936

Research contact person
Name of lead principal investigator	1st name Masafumi Middle name Last name Kitakaze
Organization	National Cerebral and Cardiovascular Center
Division name	Department of Clinical Medicine and Development
Zip code	654-8565
Address	6-1 Kishibe-Simmachi, Suita Osaka 564-8565, JAPAN
TEL	06-6170-1070
Email	kitakaze@ncvc.go.jp

Public contact
Name of contact person	1st name Masafumi Middle name Last name Kitakaze
Organization	National Cerebral and Cardiovascular Center
Division name	Department of Clinical Medicine and Development
Zip code	564-8565
Address	6-1 Kishibe-Simmachi, Suita Osaka 564-8565, JAPAN
TEL	06-6170-1070
Homepage URL
Email	kitakaze@ncvc.go.jp

Sponsor
Institute	TOPLEVEL study office
Institute
Department

Funding Source
Organization	Mitsubishi Tanabe Pharma
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

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

IRB Contact (For public release)
Organization	National Cerebral and Cardiovascular Center
Address	6-1 Kishibe-Simmachi, Suita Osaka 564-8565, JAPAN
Tel	06-6170-1070
Email	plandiv@ml.ncvc.go.jp

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	国立循環器病研究センター

Other administrative information
Date of disclosure of the study information	2014 Year 08 Month 01 Day

Related information
URL releasing protocol	http://www.toplevel.jp/
Publication of results	Unpublished

Result
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

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2014 Year 05 Month 20 Day
Date of IRB	2014 Year 06 Month 27 Day
Anticipated trial start date	2015 Year 06 Month 24 Day
Last follow-up date	2022 Year 06 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2014 Year 07 Month 18 Day
Last modified on	2020 Year 08 Month 24 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000016974