The effect of Vitamin-K1 and Colchicine on Vascular Calcification Activity in subjects with Diabetes Mellitus (ViKCoVaC): A double-blind 2x2 factorial randomized controlled trial

Jamie W Bellinge; Roslyn J Francis; Sing Ching Lee; Alistair Vickery; William Macdonald; Seng Khee Gan; Gerard T Chew; Michael Phillips; Joshua R Lewis; Gerald F Watts; Carl J Schultz

doi:10.1007/s12350-021-02589-8

The effect of Vitamin-K₁ and Colchicine on Vascular Calcification Activity in subjects with Diabetes Mellitus (ViKCoVaC): A double-blind 2x2 factorial randomized controlled trial

J Nucl Cardiol. 2022 Aug;29(4):1855-1866. doi: 10.1007/s12350-021-02589-8. Epub 2021 Apr 6.

Authors

Jamie W Bellinge^{1

2}, Roslyn J Francis^{1

3}, Sing Ching Lee^{1

2}, Alistair Vickery^{1

4}, William Macdonald⁵, Seng Khee Gan^{1

6}, Gerard T Chew^{1

6}, Michael Phillips⁷, Joshua R Lewis^{1

8

9}, Gerald F Watts^{1

10}, Carl J Schultz^{11

12}

Affiliations

¹ School of Medicine, Faculty of Health and Biomedical Science, University of Western Australia, Royal Perth Hospital Campus, M570, Po Box X2213, Perth, Western Australia, Australia.
² Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia.
³ Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
⁴ Black Swan Health, Perth, Western Australia, Australia.
⁵ Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia, Australia.
⁶ Department of Endocrinology and Diabetes, Royal Perth Hospital, Perth, Western Australia, Australia.
⁷ Harry Perkins Institute for Medical Research, and Centre for Medical Research, University of Western Australia and, Nedlands, Western Australia, Australia.
⁸ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
⁹ Centre for Kidney Research, Children's Hospital Westmead, School of Public Health, University of Sydney, Westmead, New South Wales, Australia.
¹⁰ Cardiometabolic service, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia.
¹¹ School of Medicine, Faculty of Health and Biomedical Science, University of Western Australia, Royal Perth Hospital Campus, M570, Po Box X2213, Perth, Western Australia, Australia. carl.schultz@uwa.edu.au.
¹² Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia. carl.schultz@uwa.edu.au.

PMID: 33825140
DOI: 10.1007/s12350-021-02589-8

Abstract

Background: There is currently no treatment for attenuating progression of arterial calcification. ¹⁸F-sodium fluoride positron emission tomography (¹⁸F-NaF PET) locates regions of calcification activity. We tested whether vitamin-K₁ or colchicine affected arterial calcification activity.

Methods: 154 patients with diabetes mellitus and coronary calcification, as detected using computed tomography (CT), were randomized to one of four treatment groups (placebo/placebo, vitamin-K₁ [10 mg/day]/placebo, colchicine [0.5 mg/day]/placebo, vitamin-K₁ [10 mg/day]/ colchicine [0.5 mg/day]) in a double-blind, placebo-controlled 2x2 factorial trial of three months duration. Change in coronary calcification activity was estimated as a change in coronary maximum tissue-to-background ratio (TBRmax) on ¹⁸F-NaF PET.

Results: 149 subjects completed follow-up (vitamin-K₁: placebo = 73:76 and colchicine: placebo = 73:76). Neither vitamin-K₁ nor colchicine had a statistically significant effect on the coronary TBRmax compared with placebo (mean difference for treatment groups 0·00 ± 0·16 and 0·01 ± 0·17, respectively, p > 0.05). There were no serious adverse effects reported with colchicine or vitamin-K₁.

Conclusions: In patients with type 2 diabetes, neither vitamin-K₁ nor colchicine significantly decreases coronary calcification activity, as estimated by ¹⁸F-NaF PET, over a period of 3 months.

Clinical trial registration: ACTRN12616000024448.

Keywords: Calcification; Colchicine; Molecular Imaging; Vitamin-K.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Colchicine* / therapeutic use
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Double-Blind Method
Humans
Positron Emission Tomography Computed Tomography
Sodium Fluoride
Vascular Calcification* / diagnostic imaging
Vascular Calcification* / drug therapy
Vitamin K 1*
Vitamins

Substances

Vitamins
Vitamin K 1
Sodium Fluoride
Colchicine