Folic Acid Supplementation in Calcific Aortic Valve Disease
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
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|
Phase 2 |
Detailed 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Drug group 1 Dietary Supplement: Folic acid 2.5 mg/day |
Drug: Folic Acid Oral Tablet
Dietary Supplement: Folic acid 2.5mg/day
|
Placebo Comparator: Control group 2 Dietary Supplement: Placebo |
Dietary Supplement: Placebo
Dietary Supplement: Placebo
|
Outcome Measures
Primary Outcome Measures
- Aortic valve calcification [104 weeks]
Aortic valve calcification as measured by change from baseline in Agatston arbitrary unit (AU) using cardiac computed tomography (CT) at 104 weeks
- overall survival [3 years]
overall survival (OS)
Secondary Outcome Measures
- Time-to-major adverse cardiovascular events [104 weeks]
Time-to-major adverse cardiovascular events of cardiac death, non- fatal myocardial infarction, heart failure hospitalization and stroke
- Aortic valve calcification [at week 52]
Change in aortic valve calcification as measured by Agatston AU using cardiac computed tomography (CT) at week 52
- Change in aortic valve stenosis severity [at week 104]
Change in aortic valve stenosis severity as measured by peak transaortic velocity using echocardiography at week 104 as compared to baseline
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female adult ≥ 35 years of age at the time of recruiting.
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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
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Subject provides written informed consent prior to initiation of any study procedures.
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Subject understands and agrees to comply with planned study procedures.
Exclusion Criteria:
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Subject has concomitant moderate or severe mitral or tricuspid valve disease.
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Subject has left ventricular ejection fraction < 50%.
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Subject previous history of aortic valve surgery, pancreatitis, malignant tumor, drug or alcohol abuse.
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Subjects whose alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 times the upper limit of normal range.
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Subjects who cannot undergo Cardiac CT.
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Pregnant or lactating women.
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Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Wuhan Union Hospital, China
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- Stanger O. Physiology of folic acid in health and disease. Curr Drug Metab. 2002 Apr;3(2):211-23. doi: 10.2174/1389200024605163.
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