Effects of Pioglitazone in Calcific Aortic Valve Disease

NCT ID: NCT05875675

Last Updated: 2023-05-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-01
• Study Completion Date: 2028-07-01

Brief 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.

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.

Conditions

Calcification of Aortic Valve; Aortic Valve Stenosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Drug group

Dietary Supplement: Pioglitazone 30 mg by mouth daily

Group Type: EXPERIMENTAL

Drug: Pioglitazone Oral Tablet

Intervention Type: DRUG

Dietary Supplement: Pioglitazone 30 mg by mouth daily

Control group

Dietary Supplement: Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Dietary: Supplement: Placebo

Interventions

Drug: Pioglitazone Oral Tablet

Dietary Supplement: Pioglitazone 30 mg by mouth daily

Intervention Type: DRUG

Placebo

Dietary: Supplement: Placebo

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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.

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Fei Li, MD

Role: CONTACT

lifei_union@hust.edu.cn

15972969897 ext. +86

Li Xu

Role: CONTACT

unionxuli@hust.edu.cn

15387030212 ext. +86

References

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.

Reference Type: BACKGROUND

PMID: 23288158 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33881501 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25997932 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23833295 (View on PubMed)

Other Identifiers

WUHFACAVD02

Identifier Type: -

Identifier Source: org_study_id