Effects of Pioglitazone in Calcific Aortic Valve Disease

Effect of Pioglitazone Treatment in Patient's Calcific Aortic Valve Disease With Mild Aortic Valve Stenosis

This is a prospective, randomized, comparative, clinical trial conducted by Wuhan Union Hospital that aims to evaluate the efficacy and safety of pioglitazone compared to placebo in patients with calcific aortic valve disease with mild aortic valve stenosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Aortic Valve Stenosis; Calcification of Aortic Valve
• Intervention / Treatment: Drug: Drug: Pioglitazone Oral Tablet; Dietary supplement: Placebo

Detailed Description

Pioglitazone is an oral drug for the treatment of type 2 diabetes that improves the utilization of glucose by the body by inhibiting hepatic gluconeogenesis, and has anti-inflammatory and antioxidant effects that may improve vascular endothelial cell injury and prevent cardiovascular disease. This study is to slow the process of aortic valve calcification by pioglitazone intervention with the aim of reducing the risk of aortic valve stenosis. Participants were randomized into two groups: one group was given oral pioglitazone treatment and the other group was given placebo control. Patients in both groups were observed for aortic valve calcification during the follow-up period, and changes in aortic valve thickness, degree of calcification, and flow were recorded by cardiac ultrasonography, while the incidence of cardiovascular events and adverse effects were assessed.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fei Li, MD; Phone Number: +86 15972969897; Email: lifei_union@hust.edu.cn
• Study Contact Backup: Name: Li Xu; Phone Number: +86 15387030212; Email: unionxuli@hust.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female adult ≥ 35 years of age at the time of rescruiting.
• Subject has calcific aortic valve disease with mild to moderate aortic valve stenosis as defined by Doppler echocardiography results: Aortic Valve mean pressure gradient between 10-30 mmHg and Aortic Valve Area ≥ 1.2 and ≤ 2.0 cm2 on TTE within 2 weeks prior to randomization and Cardiac Compute Tomography (CT) test results: aortic valve calcium score (Agatston score) ≥ 200 AU at baseline cardiac CT within 1 month prior to randomization
• Subject provides written informed consent prior to initiation of any study procedures.
• Subject understands and agrees to comply with planned study procedures.

Exclusion Criteria:

• Subject has concomitant moderate or severe mitral or tricuspid valve disease.
• Subject has left ventricular ejection fraction < 50%.
• Subject previous history of aortic valve surgery, pancreatitis, malignant tumor, drug or alcohol abuse.
• Subjects whose alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 times the upper limit of normal range.
• Subjects who cannot undergo Cardiac CT.
• Pregnant or lactating women.
• Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug group; Dietary Supplement: Pioglitazone 30 mg by mouth daily	Drug: Drug: Pioglitazone Oral Tablet; Dietary Supplement: Pioglitazone 30 mg by mouth daily
Placebo Comparator: Control group; Dietary Supplement: Placebo	Dietary supplement: Placebo; Dietary: Supplement: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	overall survival (OS)	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-major adverse cardiovascular events	Time-to-major adverse cardiovascular events of cardiac death, non- fatal myocardial infarction, heart failure hospitalization and stroke	104 weeks
Change in aortic valve stenosis severity	Change in aortic valve stenosis severity as measured by peak transaortic velocity using echocardiography at week 104 as compared to baseline	at week 104
HbA1c	Metabolic control	104 weeks
Glucose level	Metabolic control	104 weeks

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China

Publications and helpful links

General Publications

• Chu Y, Lund DD, Weiss RM, Brooks RM, Doshi H, Hajj GP, Sigmund CD, Heistad DD. Pioglitazone attenuates valvular calcification induced by hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):523-32. doi: 10.1161/ATVBAHA.112.300794. Epub 2013 Jan 3.
• Greenberg HZE, Zhao G, Shah AM, Zhang M. Role of oxidative stress in calcific aortic valve disease and its therapeutic implications. Cardiovasc Res. 2022 May 6;118(6):1433-1451. doi: 10.1093/cvr/cvab142.
• Hajj GP, Chu Y, Lund DD, Magida JA, Funk ND, Brooks RM, Baumbach GL, Zimmerman KA, Davis MK, El Accaoui RN, Hameed T, Doshi H, Chen B, Leinwand LA, Song LS, Heistad DD, Weiss RM. Spontaneous Aortic Regurgitation and Valvular Cardiomyopathy in Mice. Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1653-62. doi: 10.1161/ATVBAHA.115.305729. Epub 2015 May 21.
• Weiss RM, Miller JD, Heistad DD. Fibrocalcific aortic valve disease: opportunity to understand disease mechanisms using mouse models. Circ Res. 2013 Jul 5;113(2):209-22. doi: 10.1161/CIRCRESAHA.113.300153.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: May 4, 2023
• First Submitted That Met QC Criteria: May 24, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Aortic Valve Stenosis; Pioglitazone; Calcification of Aortic Valve
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Pathological Conditions, Anatomical; Heart Valve Diseases; Ventricular Outflow Obstruction; Calcium Metabolism Disorders; Aortic Valve Stenosis; Constriction, Pathologic; Aortic Valve Disease; Calcinosis; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: WUHFACAVD02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: we would like to share IPD with other researchers 1 years after the trial completely finished
• IPD Sharing Time Frame: All data should only be used for academic research.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes