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Trial registered on ANZCTR

Registration number

ACTRN12616000024448

Ethics application status

Approved

Date submitted

31/07/2015

Date registered

15/01/2016

Date last updated

18/06/2021

Date data sharing statement initially provided

5/12/2018

Type of registration

Retrospectively registered

Titles & IDs

Public title

To determine whether supplementation with oral Vitamin K and or low dose colchicine vs placebo will reduce vascular calcification activity in patients with diabetes mellitus. The ViKCoVac Diabetes Study.

Scientific title

A double blind randomised placebo controlled 2x2 factorial trial of the effect of Vitamin K and Colchicine on vascular calcification activity in patients with diabetes mellitus.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1172-7735

Trial acronym

ViKCoVaC Diabetes Study

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Diabetes Mellitus

Coronary Artery Disease

Condition category

Condition code

Cardiovascular

Coronary heart disease

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Arm 1 - Colchicine 0.5 mg orally once daily and placebo once daily
Arm 2 - Vitamin K 10mg orally once daily and placebo once daily
Arm 3 - Vitamin K 10mg orally once daily and Colchicine 0.5mg orally once daily.
Arm 4 - Placebo once daily and Placebo once daily
All interventions and placebo's are capsules and will be given for 3 months. Adherence will be monitored by pill counting and laboratory tests

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Placebo: microcellulose tablet

Control group

Placebo

Outcomes

Primary outcome [1]

Vascular Calcification activity measured by PET scan

Timepoint [1]

3 months

Secondary outcome [1]

Secondary aims are to determine the rate of accumulation of vascular calcification measured as the difference on CT (between baseline and at 2 year follow up.)

Timepoint [1]

2 years

Eligibility

Key inclusion criteria

Type 1 or type 2 diabetes mellitus

Minimum age

50 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Prior or planned treated with coronary bypass surgery or percutaneous coronary intervention.
Symptomatic coronary disease
Advanced renal disease
Known intolerance to Vit K or colchicine
Existing treatment with warfarin or another Vit K
Active cancer
Arrhythmia that precludes ECG gated PET/CT
Pregnancy
Hyperthyroidism
Current treatment for Paget' s disease,
Chronic inflammatory conditions requiring chronic intake of antibiotics,steroids or immunosupressant.
Chronic diarrhoea

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Once participants have met all inclusion criteria and signed the consent. A non contrast low dose ECG triggered MSCT scan will be performed to quantify vascular calcification. Following the PET scan participants will be randomised to Vitamin K 10mg daily or placebo in a ratio 1:1. A second randomisation will be performed to Colchicine 0.5mg or placebo.
The allocation will be in a numbered container

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Computer generated random allocation to one of 4 groups

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Factorial

Other design features

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

Descriptive statistics will be used for the baseline characterisitcs and exploratory analysis. The primary data analysis will compare the change in vascular uptake of 18F-fluoride after 3 months.
Change in vascular uptake of 18F-flouride will be measured as maximum tissue/background ratio from PET.Paired t-test and ANOVA will be used.
Sample size was based on a 2 sided 2 sample t-test. At a significance level of 0.05 the study has 90% power to detect a difference of 27 assuming a mean of 159 in the control group and and a standard deviation of 48 in both groups.

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

Actual

10/08/2015

Date of last participant enrolment

Anticipated

1/04/2018

Actual

16/05/2018

Date of last data collection

Anticipated

1/07/2021

Actual

Sample size

Target

154

Accrual to date

Final

154

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Royal Perth Hospital - Perth

Recruitment hospital [2]

Fremantle Hospital and Health Service - Fremantle

Recruitment postcode(s) [1]

6000 - Perth

Recruitment postcode(s) [2]

6160 - Fremantle

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Medical Research Foundation grant

Address [1]

197 Wellington Street
Perth CBD
6000 WA

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Perth Hospital

Address

197 Wellington street Perth
Perth CBD
6000 WA

Country

Australia

Secondary sponsor category [1]

Commercial sector/Industry

Name [1]

Aspen Pharmacare Australia

Address [1]

34-36 Chandos street
St Leonards
2065 NSW

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Perth Hospital

Ethics committee address [1]

Level 5 Colonial House
Royal Perth Hospital
Wellington street
Perth WA
6000
Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/07/2014

Approval date [1]

30/09/2014

Ethics approval number [1]

REG 14-095

Summary

Brief summary

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality in the Western World and diabetes mellitus confers a doubling of CVD risk.  Vascular calcification (VC) or hardening of the arteries is one of the most powerful independent predictors of cardiovascular events.  VC is accelerated in patients with diabetes mellitus advancing vascular age by 5-10 years above chronological age. Progression of coronary calcification is associated with an adverse prognosis that is proportional to the rate of increase of coronary calcification over and above baseline calcification levels, indicating a pressing need for novel preventative therapies.  The prevention of VC is a novel target that may effectively reduce risk of vascular events.  Active vascular calcium deposition as opposed to stable patches of calcium may be detected with 18F-Fluoride PET/CT.  This randomized double-blind placebo controlled 2x2 factorial trial will evaluate 2 novel therapies targeting a reduction of VC activity:  Vitamin-K (VitK) 10mg per day targeting the increased activation of MGP, a potent local inhibitor of VC, and Colchicine 0.5mg per day, targeting inflammation via the accumulation of white blood cells in atherosclerotic plaque, a prerequisite for calcification. The effect of active treatment vs placebo for 3 months on the vascular calcification activity measured by PET-scan will be tested.  Subsequently a natural history study will aim to define in a local patients with contemporary preventative treatment the rate of accumulation of VC (measured as the difference on Computed tomography (CT) between baseline and at 2y follow up).  The study will be coordinated from the Department of Cardiology, Royal Perth Hospital.  

This study aims to determine whether one of these two novel therapies will reduce vascular calcification activity measured by positron-emission tomography/computed tomography (PET/CT) scan at baseline and after 3 months of:
Oral Vitamin-K 10mg/day  vs. placebo in patients with DM
Oral colchicine 0.5mg/day vs. placebo in patients with DM
Secondary aims are to determine the rate of accumulation of VC (measured as the difference on CT scan between baseline and at the 2yr follow-up).

Patients with diabetes (type I, type II), aged 50 – 80yrs , will be approached at their regular clinic visit or during a hospital admission.
Once randomised, they will be telephoned at 1 and 2 weeks to assess compliance, then asked to return to the cardiology clinic at 1, 2 and 3 months.  Blood tests will be performed at 1 and 3 months.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Carl Schultz

Address

Royal Perth Hospital
Department of Cardiology
197 Wellington street
Perth
6000
Western Australia
Australia

Country

Australia

Phone

+618 9224-2067

Fax

+618 9224-2448

[email protected]

Contact person for public queries

Name

Carl Schultz

Address

Royal Perth Hospital
Department of Cardiology
Wellington street
Perth
6000
Western Australia
Australia

Country

Australia

Phone

+618 9224-2067

Fax

+618 9224-2448

[email protected]

Contact person for scientific queries

Name

Carl Schultz

Address

Royal Perth Hospital
Department of Cardiology
Wellington street
Perth
6000
Western Australia

Country

Australia

Phone

+618 9224-2067

Fax

+618 9224-2448

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Impact of Incidental Coronary Artery Calcification on CT Pulmonary Angiography	2019	https://doi.org/10.1016/j.hlc.2019.06.277
Dimensions AI	Improving Risk Stratification in Patients with Diabetes Mellitus; an 18F-Sodium Fluoride Positron Emission Tomography Study	2019	https://doi.org/10.1016/j.hlc.2019.06.278
Embase	18F-sodium fluoride positron emission tomography activity predicts the development of new coronary artery calcifications.	2021	https://dx.doi.org/10.1161/ATVBAHA.120.315364
Embase	The effect of vitamin K1on arterial calcification activity in subjects with diabetes mellitus: a post hoc analysis of a double-blind, randomized, placebo-controlled trial.	2022	https://dx.doi.org/10.1093/ajcn/nqab306
Embase	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.	2022	https://dx.doi.org/10.1007/s12350-021-02589-8

N.B. These documents automatically identified may not have been verified by the study sponsor.

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