Folic Acid Supplementation in Calcific Aortic Valve Disease

Aortic Valve Stenosis Clinical Trial

Official title:

Effect of Folic Acid Supplementation in Patient's Calcific Aortic Valve Disease With Mild Aortic Valve Stenosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05861648
• Other study ID #: WUHFACAVD01
• 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 folic acid compared to placebo in patients with calcific aortic valve disease with mild aortic valve stenosis.

Description:

Folic acid is involved in important physiological activities in the body such as DNA synthesis, cell division and growth and development. Recent studies have shown that folic acid may also have a positive effect on cardiovascular system health. Aortic valve calcification is a cardiovascular disease whose incidence increases progressively with age. Early studies suggest that folic acid may slow the progression of aortic valve calcification by inhibiting cell calcification and promoting calcium deposition. Participants were randomized into two groups: one group was given oral folic acid 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 recruiting.
• 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 transthoracic echocardiography 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:
• Folic Acid Oral Tablet
Dietary Supplement: Folic acid 2.5mg/day

Dietary Supplement:
• Placebo
Dietary Supplement: Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

References & Publications (5)

Gao L, Chalupsky K, Stefani E, Cai H. Mechanistic insights into folic acid-dependent vascular protection: dihydrofolate reductase (DHFR)-mediated reduction in oxidant stress in endothelial cells and angiotensin II-infused mice: a novel HPLC-based fluorescent assay for DHFR activity. J Mol Cell Cardiol. 2009 Dec;47(6):752-60. doi: 10.1016/j.yjmcc.2009.07.025. Epub 2009 Aug 3. — View Citation

Gao L, Siu KL, Chalupsky K, Nguyen A, Chen P, Weintraub NL, Galis Z, Cai H. Role of uncoupled endothelial nitric oxide synthase in abdominal aortic aneurysm formation: treatment with folic acid. Hypertension. 2012 Jan;59(1):158-66. doi: 10.1161/HYPERTENSIONAHA.111.181644. Epub 2011 Nov 14. — View Citation

Moens AL, Claeys MJ, Wuyts FL, Goovaerts I, Van Hertbruggen E, Wendelen LC, Van Hoof VO, Vrints CJ. Effect of folic acid on endothelial function following acute myocardial infarction. Am J Cardiol. 2007 Feb 15;99(4):476-81. doi: 10.1016/j.amjcard.2006.08.057. Epub 2006 Dec 28. — View Citation

Shirodaria C, Antoniades C, Lee J, Jackson CE, Robson MD, Francis JM, Moat SJ, Ratnatunga C, Pillai R, Refsum H, Neubauer S, Channon KM. Global improvement of vascular function and redox state with low-dose folic acid: implications for folate therapy in patients with coronary artery disease. Circulation. 2007 May 1;115(17):2262-70. doi: 10.1161/CIRCULATIONAHA.106.679084. Epub 2007 Apr 9. — View Citation

Stanger O. Physiology of folic acid in health and disease. Curr Drug Metab. 2002 Apr;3(2):211-23. doi: 10.2174/1389200024605163. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aortic valve calcification	Aortic valve calcification as measured by change from baseline in Agatston arbitrary unit (AU) using cardiac computed tomography (CT) at 104 weeks	104 weeks
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	Aortic valve calcification	Change in aortic valve calcification as measured by Agatston AU using cardiac computed tomography (CT) at week 52	at week 52
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