search
Back to results

Folic Acid Supplementation in Calcific Aortic Valve Disease

Primary Purpose

Calcification of Aortic Valve, Aortic Valve Stenosis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Folic Acid Oral Tablet
Placebo
Sponsored by
Wuhan Union Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Calcification of Aortic Valve focused on measuring Folic Acid, Calcification of Aortic Valve, Aortic Valve Stenosis

Eligibility Criteria

35 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Drug group 1

    Control group 2

    Arm Description

    Dietary Supplement: Folic acid 2.5 mg/day

    Dietary Supplement: Placebo

    Outcomes

    Primary Outcome Measures

    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
    overall survival
    overall survival (OS)

    Secondary Outcome Measures

    Time-to-major adverse cardiovascular events
    Time-to-major adverse cardiovascular events of cardiac death, non- fatal myocardial infarction, heart failure hospitalization and stroke
    Aortic valve calcification
    Change in aortic valve calcification as measured by Agatston AU using cardiac computed tomography (CT) at week 52
    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

    Full Information

    First Posted
    May 4, 2023
    Last Updated
    May 16, 2023
    Sponsor
    Wuhan Union Hospital, China
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05861648
    Brief Title
    Folic Acid Supplementation in Calcific Aortic Valve Disease
    Official Title
    Effect of Folic Acid Supplementation in Patient's Calcific Aortic Valve Disease With Mild Aortic Valve Stenosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 1, 2023 (Anticipated)
    Primary Completion Date
    July 1, 2025 (Anticipated)
    Study Completion Date
    July 1, 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Wuhan Union Hospital, China

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    Yes

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Calcification of Aortic Valve, Aortic Valve Stenosis
    Keywords
    Folic Acid, Calcification of Aortic Valve, Aortic Valve Stenosis

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Drug group 1
    Arm Type
    Experimental
    Arm Description
    Dietary Supplement: Folic acid 2.5 mg/day
    Arm Title
    Control group 2
    Arm Type
    Placebo Comparator
    Arm Description
    Dietary Supplement: Placebo
    Intervention Type
    Drug
    Intervention Name(s)
    Folic Acid Oral Tablet
    Intervention Description
    Dietary Supplement: Folic acid 2.5mg/day
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Placebo
    Intervention Description
    Dietary Supplement: Placebo
    Primary Outcome Measure Information:
    Title
    Aortic valve calcification
    Description
    Aortic valve calcification as measured by change from baseline in Agatston arbitrary unit (AU) using cardiac computed tomography (CT) at 104 weeks
    Time Frame
    104 weeks
    Title
    overall survival
    Description
    overall survival (OS)
    Time Frame
    3 years
    Secondary Outcome Measure Information:
    Title
    Time-to-major adverse cardiovascular events
    Description
    Time-to-major adverse cardiovascular events of cardiac death, non- fatal myocardial infarction, heart failure hospitalization and stroke
    Time Frame
    104 weeks
    Title
    Aortic valve calcification
    Description
    Change in aortic valve calcification as measured by Agatston AU using cardiac computed tomography (CT) at week 52
    Time Frame
    at week 52
    Title
    Change in aortic valve stenosis severity
    Description
    Change in aortic valve stenosis severity as measured by peak transaortic velocity using echocardiography at week 104 as compared to baseline
    Time Frame
    at week 104

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    35 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Fei Li, MD
    Phone
    15972969897
    Ext
    +86
    Email
    lifei_union@hust.edu.cn
    First Name & Middle Initial & Last Name or Official Title & Degree
    Li Xu, MD
    Phone
    15387030212
    Ext
    +86
    Email
    unionxuli@hust.edu.cn

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    we would like to share individual participant data with other researchers 1 years after the trial completely finished
    IPD Sharing Access Criteria
    All data should only be used for academic research.
    Citations:
    PubMed Identifier
    19660467
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    17293188
    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.
    Results Reference
    background
    PubMed Identifier
    17420345
    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.
    Results Reference
    background
    PubMed Identifier
    12003352
    Citation
    Stanger O. Physiology of folic acid in health and disease. Curr Drug Metab. 2002 Apr;3(2):211-23. doi: 10.2174/1389200024605163.
    Results Reference
    background
    PubMed Identifier
    22083158
    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.
    Results Reference
    background

    Learn more about this trial

    Folic Acid Supplementation in Calcific Aortic Valve Disease

    We'll reach out to this number within 24 hrs