Randomized, Open-label Trial of Inhibitory Effect of Evogliptin on Progression of CAVD

August 19, 2020 updated by: Jae-Kwan Song, Asan Medical Center

An Open-label, Randomized Study of Inhibitory Effect of Evogliptin, the Dipeptidyl Peptidase-4 Inhibitor, on the Progression of Aortic Valve Calcification in Patients With Type 2 Diabetes Mellitus and Mild-to-moderate Aortic Stenosis

The purpose of this study is to assess an inhibitory effect of Evogliptin on the progression of mild-to-moderate aortic stenosis in patients with T2DM and calcific aortic stenosis.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Despite a lot of clinician's efforts to develop an effective medical treatment of calcific aortic valve disease (CAVD) for decades, there is no scientifically-proved medical treatment yet. Since the pathological features of CAVD are characterized by inflammatory cell infiltration and lipid deposition, as in atherosclerosis, statin drugs that are proved to be effective in the treatment of cardiovascular disease, have been used in the most recent randomized clinical trials; however, different types of medications showed negative results and thus, CAVD represents an unmet clinical need.

Researchers of Asan Medical Center have proved that dipeptidyl-peptidase-4 (DPP-4)-IGF (insulin-like growth factor)-1 axis is important for pathologic osteoblast transformation of valvular interstitial cell (VIC), and reported that the administration of DPP-4 inhibitor prevents the calcification effectively in the actual animal model of CAVD. Under a normal condition, IGF-1 suppresses the pathologic transformation of VIC; however, when endothelial cells are damaged due to aging or various pathological conditions, DPP-4 expression is increased in valvular tissue. Since DPP-4 acts as an enzyme that degrades IGF-1, it reduces normal IGF-1 activity and increases transformation of VIC to osteoblast, causing pathological calcification and worsening CAVD.

After comparing six different DPP-4 inhibitors, researchers of Asan Medical Center discovered that evogliptin has higher cardiac tissue distribution compared to other DPP-4 inhibitors. In addition, the DPP-4 inhibitors with high cardiac tissue distribution have shown decreased incidence rate of severe CAVD in the retrospective study. Based on these findings, this study will examine the effect of evogliptin on progression of CAVD.

The study is a randomized, open-label trial of evogliptin in subjects with T2DM and moderate-to-severe CAVD. Subjects who have agreed to participate in the study and signed the ICF will undergo a screening period and those who meet the eligibility criteria will be randomized in a 1:1 ratio to evogliptin or non-evogliptin group. The subjects will take the drug for 96 weeks and will be closely monitored for efficacy. The effectiveness of evogliptin on inhibition of CAVD progression will be evaluated by comparing the change in aortic valve calcium volume in the evogliptin group against that of the non-evogliptin group.

Study Type

Interventional

Enrollment (Anticipated)

218

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male and female aged 19 years or older
  2. Subjects who were diagnosed with type 2 diabetes mellitus and being treated with oral hypoglycemic drugs

  3. Subjects whose Doppler echocardiography or Heart CT performed within 8 weeks prior to or during Screening Visit (Visit 1) is satisfying any of the followings:

    • Doppler echocardiogrphy (aortic valve calcification and/or hypertrophy with aortic peak velocity≥2.0 m/s); or
    • Heart CT (aortic valve calcium score≥300 AU)
  4. Subjects who decided to take part in this study on his/her own volition after listening to the details of this study

Exclusion Criteria:

  1. Subjects with severe aortic valve stenosis (aortic peak velocity>4.0 m/s, mean pressure gradient >40 mmHg, or aortic valve area≤0.75 cm2)
  2. Subjects with left ventricular ejection fraction < 40%
  3. Heart failure patients: Subjects with heart failure of NYHA functional class II-IV
  4. Subjects with an estimated glomerular filtration rate (eGFR) of <30ml
  5. Subjects with type 1 diabetes or diabetic ketoacidosis
  6. Subjects with serious hypersensitivity to DPP-4 inhibitors

  7. Subjects who have received/are receiving any of the following medication therapies:

    • Vitamin K
    • Calcium supplement (or osteoporosis medication)
  8. Subjects whose aortic valve stenosis is not caused by degenerative or bicuspid valve disease (e.g. rheumatic valve disease)
  9. Subjects who have received or are expected to receive (as of Visit 1) aortic valve surgery during the study.
  10. Subjects for whom a two-year clinical course investigation is not possible due to malignant tumor or cerebrovascular disease
  11. Pregnant or lactating women

  12. Women of childbearing potential who are sexually active and do not agree to use proper contraception during the study

    • Proper contraception means physical barrier method including condom, contraceptive diaphragm or cervix cap. The use of contraceptive or oral contraceptive containing hormones that may induce drug-drug interaction with the investigational product is not allowed during the study (with the exception of an oral contraceptive administered to cure menopausal symptoms, only if the dosage has been consistent for the past 8 weeks)
  13. Any other subjects deemed not eligible for this study by an investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Evogliptin Group
evogliptin 5mg daily
Drug: Evogliptin
Subjects will receive evogliptin 5 mg daily
No Intervention: Non-evogliptin Group
DM medications except evogliptin and other DPP-4 inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in aortic valve calcium volume at week 96 from baseline
Time Frame: 96 weeks
96 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in aortic valve calcium volume at week 48 from baseline
Time Frame: 96 weeks
96 weeks
Change in aortic valve calcium score at week 48 and week 96 from baseline
Time Frame: 48 weeks, 96 weeks
48 weeks, 96 weeks
Rate of change (%) in aortic valve calcium volume at week 48 and week 96 from baseline
Time Frame: 48 weeks, 96 weeks
48 weeks, 96 weeks
Change in peak aortic-jet velocity at week 48 and week 96 from baseline
Time Frame: 48 weeks, 96 weeks
48 weeks, 96 weeks
Change in aortic peak & mean pressure gradient at week 48 and week 96 from baseline
Time Frame: 48 weeks, 96 weeks
48 weeks, 96 weeks
Change in aortic valve area at week 48 and week 96 from baseline
Time Frame: 48 weeks, 96 weeks
48 weeks, 96 weeks
Time of major cardiovascular event
Time Frame: anytime during the entire follow-up of 96 weeks
anytime during the entire follow-up of 96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Collaborators

REDNVIA Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 1, 2020

Primary Completion (Anticipated)

September 1, 2024

Study Completion (Anticipated)

September 1, 2024

Study Registration Dates

First Submitted

August 19, 2020

First Submitted That Met QC Criteria

August 19, 2020

First Posted (Actual)

August 20, 2020

Study Record Updates

Last Update Posted (Actual)

August 20, 2020

Last Update Submitted That Met QC Criteria

August 19, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • DIP_CAVD_DM

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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