TY - JOUR

T1 - Study protocol of the InterVitaminK trial

T2 - 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

AU - Kampmann, Freja Bach

AU - Thysen, Sanne Marie

AU - Nielsen, Camilla Friis Bryde

AU - Kofoed, Klaus Fuglsang

AU - Køber, Lars

AU - Pham, Michael Huy Cuong

AU - Vaag, Allan

AU - Jørgensen, Niklas Rye

AU - Petersen, Janne

AU - Jacobsen, Rikke Kart

AU - Kårhus, Line Lund

AU - Diederichsen, Axel

AU - Frimodt-Møller, Marie

AU - Linneberg, Allan

N1 - Funding Information: AL is sponsor and principal investigator (mail: allan.linneberg@regionh.dk, Phone: +45 38 16 31 18. Centre for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, DK-2000, Frederiksberg, Denmark). At present, the trial is supported by grants from the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation (grant number NNF20SA0067242) and The Danish Heart Foundation; the Capital Region of Denmark (grant number: A7105), Bispebjerg and Frederiksberg Hospital (grant number: N/A, date for receiving grants: 5 January 2022); Jascha Fonden (grant number: N/A, date for receiving grants: 15 June 2022); Independent Research Fund Denmark (DFF-1) (grant number: 2096-00009A) Martha and Hans Peter Johnsen Fond (grant number: N/A, date for receiving the grant 5 December 2022) and Kappa Bioscience AS (Oslo, Norway) (grant number: N/A). Kappa Bioscience AS. provided the trial tablets (MK-7 and placebo). Publisher Copyright: © 2023 BMJ Publishing Group. All rights reserved.

PY - 2023

Y1 - 2023

N2 - Introduction Vitamin 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 analysis The 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 dissemination Oral 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 number NCT05259046.

AB - Introduction Vitamin 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 analysis The 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 dissemination Oral 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 number NCT05259046.

KW - Calcium & bone

KW - CARDIOLOGY

KW - General endocrinology

KW - NUTRITION & DIETETICS

U2 - 10.1136/bmjopen-2023-071885

DO - 10.1136/bmjopen-2023-071885

M3 - Journal article

C2 - 37208133

AN - SCOPUS:85159691396

VL - 13

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 5

M1 - e071885

ER -