Folic Acid Supplementation in Calcific Aortic Valve Disease

NCT05861648 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: WUHFACAVD01
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Calcification of Aortic Valve; Aortic Valve Stenosis

Keywords

Folic Acid; Calcification of Aortic Valve; Aortic Valve Stenosis

Outcome Measures

Primary Outcomes (2)

• 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

• overall survival

  overall survival (OS)

  3 years

Secondary Outcomes (3)

• Time-to-major adverse cardiovascular events

  104 weeks

• Aortic valve calcification

  at week 52

• Change in aortic valve stenosis severity

  at week 104

Study Arms (2)

Drug group 1

EXPERIMENTAL

Dietary Supplement: Folic acid 2.5 mg/day

Drug: Folic Acid Oral Tablet

Control group 2

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Dietary Supplement: Placebo

Interventions

Folic Acid Oral Tablet DRUG

Dietary Supplement: Folic acid 2.5mg/day

Drug group 1

Placebo DIETARY_SUPPLEMENT

Dietary Supplement: Placebo

Control group 2

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Related 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.

  PMID: 19660467 BACKGROUND

• 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.

  PMID: 17293188 BACKGROUND

• 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.

  PMID: 17420345 BACKGROUND

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

  PMID: 12003352 BACKGROUND

• 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.

  PMID: 22083158 BACKGROUND

MeSH Terms

Conditions

Aortic Valve, Calcification of; Aortic Valve Stenosis

Interventions

Folic Acid

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Fei Li, MD

CONTACT

15972969897; lifei_union@hust.edu.cn

Li Xu, MD

CONTACT

15387030212; unionxuli@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2023
• First Posted: May 17, 2023
• Study Start: July 1, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 17, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Access Criteria: All data should only be used for academic research.