Effects of Pioglitazone in Calcific Aortic Valve Disease

Aortic Valve Stenosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05875675
• Other study ID #: WUHFACAVD02
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2023
• Est. completion date: July 1, 2028

Study information

• Verified date: April 2023
• Source: Wuhan Union Hospital, China
• Contact: Fei Li, MD
• Phone: 15972969897
• Email: lifei_union[@]hust.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: July 1, 2028
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aortic Valve Disease
• Aortic Valve Stenosis
• Calcinosis
• Constriction, Pathologic

Intervention

Drug:
• Drug: Pioglitazone Oral Tablet
Dietary Supplement: Pioglitazone 30 mg by mouth daily

Dietary Supplement:
• Placebo
Dietary: Supplement: Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival	overall survival (OS)	3 years
Secondary	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
Secondary	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
Secondary	HbA1c	Metabolic control	104 weeks
Secondary	Glucose level	Metabolic control	104 weeks