Teneligliptin on the Progressive Left Ventricular Diastolic Dysfunction With Type 2 Diabetes Mellitus Study (TOPLEVEL)

Clinical Study for the Effect of Teneligliptin on the Left Ventricular Diastolic Dysfunction in Patients With Type 2 Diabetes Mellitus

This is the clinical trial designed to assess the cardiac diastolic function of long term treatment with teneligliptin compared to that without teneligliptin in patients with type 2 diabetes mellitus by two arms; one includes patients showing E/e' by echocardiography less than 8, the other includes patients showing E/e' by echocardiography more than 8.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Teneligliptin

• Study Type: Interventional
• Enrollment (Anticipated): 936
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Miki Imazu, M.D., Ph.D.; Phone Number: 2225 81-6-6833-5012; Email: mimadu@ncvc.go.jp

Study Locations

• Japan
  • Suita, Japan, 565-8565
    • Recruiting
    • National Cerebral and Cardiovascular Center
    • Contact: Satoshi Yasuda, M.D.; Phone Number: 06-6833-5012; Email: yasuda.satoshi.hp@ncvc.go.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Asians aged from 20 to 85 years old at baseline
• 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).

• Patients with left ventricular ejection fraction more than 40%
• Patients with written informed consent

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 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Teneligliptin in the inhibition test; Patients showing E/e' by echocardiography less than 8 at base line and assigned as Teneligliptin treatment by randomization	Drug: Teneligliptin
No Intervention: Other agents 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
Experimental: Teneligliptin in the improvement test; Patients showing E/e' by echocardiography more than 8 at base line and assigned as Teneligliptin treatment by randomization	Drug: Teneligliptin
No Intervention: Other agents 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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')	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Total number of all-cause death	Up to 2 years
Total number of deaths by cardiovascular events	Up to 2 years
Total number of all-cause hospitalization	Up to 2 years
Total number of hospitalization by cardiovascular events	Up to 2 years
Total number of hospitalization by progression of heart failure	Up to 2 years
Total number of incidents for the addition or increase of the agents for heart failure by progression of heart failure	Up to 2 years
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	Up to 2 years
Change of the deceleration time (DT) by echocardiography	Up to 2 years
Change of the left atrium volume (LAV) by echocardiography	Up to 2 years
Change of the left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs) and fractional shortening (%FS) by echocardiography	Up to 2 years
Change of the left ventricular mass index (LVMI) by echocardiography	Up to 2 years
Change of NYHA functional class	Up to 2 years
Change of plasma levels of NT-proBNP	Up to 2 years

Collaborators and Investigators

• Sponsor: National Cerebral and Cardiovascular Center

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: May 17, 2015
• First Submitted That Met QC Criteria: May 17, 2015
• First Posted (Estimate): May 20, 2015

Study Record Updates

• Last Update Posted (Actual): August 22, 2018
• Last Update Submitted That Met QC Criteria: August 20, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: M26-43