Clinical trial NCT05875675: Effects of Pioglitazone in Calcific Aortic Valve Disease
Official title: Effect of Pioglitazone Treatment in Patient's Calcific Aortic Valve Disease With Mild Aortic Valve Stenosis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Calcification of Aortic Valve
Aortic Valve Stenosis
Keywords: Calcification of Aortic Valve
Aortic Valve Stenosis
Pioglitazone
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2023-05-25
Enrollment: 100
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: overall survival
timeFrame: 3 years
Secondary outcomes:
measure: Time-to-major adverse cardiovascular events
timeFrame: 104 weeks
measure: Change in aortic valve stenosis severity
timeFrame: at week 104
measure: HbA1c
timeFrame: 104 weeks
measure: Glucose level
timeFrame: 104 weeks
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
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.
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.
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.