Study protocol of the InterVitaminK trial: a Danish population-based randomised double-blinded placebo-controlled trial of the effects of vitamin K (menaquinone-7) supplementation on cardiovascular, metabolic and bone health

• Published in: BMJ open Vol. 13; no. 5; p. e071885
• Main Authors: Kampmann, Freja Bach, Thysen, Sanne Marie, Nielsen, Camilla Friis Bryde, Kofoed, Klaus Fuglsang, Køber, Lars, Pham, Michael Huy Cuong, Vaag, Allan, Jørgensen, Niklas Rye, Petersen, Janne, Jacobsen, Rikke Kart, Kårhus, Line Lund, Diederichsen, Axel, Frimodt-Møller, Marie, Linneberg, Allan
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 19-05-2023; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Protocol
• Subjects: Bone Density; Calcification; Calcium & bone; Cardiac and Cardiovascular Systems; CARDIOLOGY; Cardiovascular disease; Cardiovascular Medicine; Chronic obstructive pulmonary disease; Clinical Medicine; Consent; Coronary Artery Disease - drug therapy; Coronary vessels; Denmark; Dietary Supplements; Disease prevention; Double-Blind Method; Female; Fractures; General endocrinology; Glucose; Health care; Humans; Intervention; Kardiologi; Klinisk medicin; Lung; Male; Medical and Health Sciences; Medical imaging; Medicin och hälsovetenskap; Metabolism; Mortality; NUTRITION & DIETETICS; Observational studies; Older people; Population-based studies; Proteins; Randomized Controlled Trials as Topic; Vascular Calcification - prevention & control; Veins & arteries; Vitamin K; Vitamin K 2 - pharmacology; Vitamin K 2 - therapeutic use; Denmark; Calcium & bone; NUTRITION & DIETETICS; CARDIOLOGY; General endocrinology
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2023-071885

IntroductionVitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few well-powered randomised controlled trials have examined whether vitamin K prevents progression of vascular calcification in individuals from the general population. The aim of the InterVitaminK trial is to investigate the effects of vitamin K supplementation (menaquinone-7, MK-7) on cardiovascular, metabolic, respiratory and bone health in a general ageing population with detectable vascular calcification.Methods and analysisThe InterVitaminK trial is a randomised, double-blinded, placebo-controlled, trial. A total of 450 men and women aged 52–82 years with detectable coronary artery calcification (CAC), but without manifest CVD, will be randomised (1:1) to receive daily MK-7 (333 µg/day) or placebo tablets for 3 years. Health examinations are scheduled at baseline, and after 1, 2 and 3 years of intervention. Health examinations include cardiac CT scans, measurements of arterial stiffness, blood pressure, lung function, physical function, muscle strength, anthropometric measures, questionnaires on general health and dietary intake, and blood and urine sampling. The primary outcome is progression of CAC from baseline to 3-year follow-up. The trial has 89% power to detect a between-group difference of at least 15%. Secondary outcomes are bone mineral density, pulmonary function and biomarkers of insulin resistance.Ethics and disseminationOral MK-7 supplementation is considered safe and has not been found to cause severe adverse events. The Ethical Committee of the Capital Region (H-21033114) approved the protocol. Written informed consent is obtained from all participants and the trial is conducted in accordance with the Declaration of Helsinki II. Both negative and positive findings will be reported.Trial registration numberNCT05259046.