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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
Date results information 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] 286976 0
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 295435 0
Coronary Artery Disease 295436 0
Condition category
Condition code
Cardiovascular 295688 295688 0 0
Coronary heart disease
Metabolic and Endocrine 296238 296238 0 0
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] 292182 0
Treatment: Drugs
Comparator / control treatment
Placebo: microcellulose tablet
Control group
Placebo

Outcomes
Primary outcome [1] 295396 0
Vascular Calcification activity measured by PET scan
Timepoint [1] 295396 0
3 months
Secondary outcome [1] 315509 0
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] 315509 0
2 years

Eligibility
Key inclusion criteria
Type 1 or type 2 diabetes mellitus
Minimum age
50 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 3969 0
Royal Perth Hospital - Perth
Recruitment hospital [2] 4119 0
Fremantle Hospital and Health Service - Fremantle
Recruitment postcode(s) [1] 9873 0
6000 - Perth
Recruitment postcode(s) [2] 10046 0
6160 - Fremantle

Funding & Sponsors
Funding source category [1] 291535 0
Charities/Societies/Foundations
Name [1] 291535 0
Medical Research Foundation grant
Address [1] 291535 0
197 Wellington Street
Perth CBD
6000 WA
Country [1] 291535 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
197 Wellington street Perth
Perth CBD
6000 WA
Country
Australia
Secondary sponsor category [1] 290214 0
Commercial sector/Industry
Name [1] 290214 0
Aspen Pharmacare Australia
Address [1] 290214 0
34-36 Chandos street
St Leonards
2065 NSW
Country [1] 290214 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293075 0
Royal Perth Hospital
Ethics committee address [1] 293075 0
Level 5 Colonial House
Royal Perth Hospital
Wellington street
Perth WA
6000
Australia
Ethics committee country [1] 293075 0
Australia
Date submitted for ethics approval [1] 293075 0
16/07/2014
Approval date [1] 293075 0
30/09/2014
Ethics approval number [1] 293075 0
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 58358 0
Prof Carl Schultz
Address 58358 0
Royal Perth Hospital
Department of Cardiology
197 Wellington street
Perth
6000
Western Australia
Australia
Country 58358 0
Australia
Phone 58358 0
+618 9224-2067
Fax 58358 0
+618 9224-2448
Email 58358 0
Carl.schultz@health.wa.gov.au
Contact person for public queries
Name 58359 0
Prof Carl Schultz
Address 58359 0
Royal Perth Hospital
Department of Cardiology
Wellington street
Perth
6000
Western Australia
Australia
Country 58359 0
Australia
Phone 58359 0
+618 9224-2067
Fax 58359 0
+618 9224-2448
Email 58359 0
Carl.schultz@health.wa.gov.au
Contact person for scientific queries
Name 58360 0
Prof Carl Schultz
Address 58360 0
Royal Perth Hospital
Department of Cardiology
Wellington street
Perth
6000
Western Australia
Country 58360 0
Australia
Phone 58360 0
+618 9224-2067
Fax 58360 0
+618 9224-2448
Email 58360 0
Carl.schultz@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary