Condition category
Surgery
Date applied
20/09/2017
Date assigned
26/09/2017
Last edited
06/09/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Reduced kidney function (sometimes called chronic kidney disease) is common, especially as people get older. Kidney problems don’t just affect the kidney, but can affect the health of blood vessels and the heart, leading to an increased risk of heart disease or strokes. After a kidney transplant, this risk of heart disease is reduced a little bit, but patients with kidney transplants are still at higher risk compared to the general population. Kidney problems also lead to blood vessels becoming stiffer than usual, due to a build-up of calcium (rather like chalk) in the wall of the blood vessel. There are no good treatments for this problem yet. Some recent research suggests that vitamin K—a vitamin present in vegetables and dairy foods—might be able to slow down or stop this build-up of calcium in blood vessels. The aim of this study is to examine whether giving extra vitamin K, which is also known as menadiol diphosphate, can affect blood vessel stiffness (which is linked to improving cardiovascular health and survival) and other measures of heart and vessel health.

Who can participate?
Adults aged 18 and older in the Glasgow area who have had a functioning kidney transplant for a year or more will be taking part.

What does the study involve?
Participants are randomly allocated to one of two groups, to receive either a vitamin K or placebo capsule three times per week. There are up to five visits to the hospital in this time, and up to two additional, brief meetings to hand out more study medication, like collecting a prescription. Most participants have have a screening visit combined with a baseline visit, and if happy to participate, have blood and urine tests taken, blood vessel stiffness measured using a small, plastic pencil-shaped device and inflatable cuffs placed on the arm and the leg, and they will attend for an MRI and CT scan of the heart, to measure blood vessel stiffness and calcification. They have transplant function and immunosuppression levels checked one month after starting to ensure the medication is not interfering with their renal transplant (this is not expected). Participants attend for a review - without any additional tests - at 6 months, when they are given more study medication. The final review takes place at 12 months when all the baseline tests are repeated.

What are the possible benefits and risks of participating?
The dose of vitamin K has been used before and is known to be safe. There is a small excess risk of jaundice (yellow appearance of your skin), more common in participants with a particular genetic condition, and people with this condition will not be able to participate in the study. Some participants may experience some bruising or discomfort when having blood tests taken. Some people find the blood pressure cuff a little uncomfortable. The MRI scan is conducted in a narrow tunnel that can be quite noisy, and some people may find this claustrophobic. We ask for two CT scans of the heart and large vessels during the study. These CT scans expose participants to a small amount of radiation, equivalent to the amount the average person is exposed to in 4-6 months from natural sources in the environment. The excess radiation exposes you to a tiny increased risk of developing cancer of 1 in 9000. This is equivalent to the risk of dying from an insect bite.

Where is the study run from?
University of Glasgow, Scotland (UK)

When is the study starting and how long is it expected to run for?
September 2017 to August 2018

Who is funding the study?
1. Kidney Research UK (UK)
2. Darlinda's Charity for Renal Research (UK)

Who is the main contact?
Dr Jennifer Lees
jennifer.lees@glasgow.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Jennifer Lees

ORCID ID

http://orcid.org/0000-0001-6331-0178

Contact details

Room 312
BHF GCRC
University of Glasgow
126 University Avenue
Glasgow
G12 8TA
United Kingdom
+44 141 330 2409
jennifer.lees@glasgow.ac.uk

Type

Scientific

Additional contact

Dr Jennifer Lees

ORCID ID

Contact details

Room 312
BHF GCRC
University of Glasgow
126 University Avenue
Glasgow
G12 8TA
United Kingdom
+44 141 330 2409
jennifer.lees@glasgow.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

GN16RE696

Study information

Scientific title

Vitamin K in kidney Transplant Organ Recipients: Investigating vEssel Stiffness

Acronym

ViKTORIES

Study hypothesis

Hypothesis:
1. Vitamin K supplementation in renal transplant patients will reduce markers of vascular stiffness and calcification in prevalent renal transplant patients compared with placebo.
2. There will be secondary beneficial effects on transplant function and LV mass/cardiac fibrosis as assessed by magnetic resonance imaging.

Ethics approval

West of Scotland Research Ethics Committee 4, 22/06/2017, ref: 17/WS/0101

Study design

Single-centre parallel-group randomised double-blind placebo-controlled trial of vitamin K4 (Menadiol diphosphate) versus placebo

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format. Please use contact details to request a participant information sheet.

Condition

Renal transplant recipients

Intervention

Most participants have a screening visit combined with a baseline visit, and if happy to participate, have blood and urine tests taken, blood vessel stiffness measured using a small, plastic pencil-shaped device and inflatable cuffs placed on the arm and the leg, and they will attend for an MRI and CT scan of the heart, to measure blood vessel stiffness and calcification.

Participants are randomised to consuming either identical capsules containing vitamin K4 (menadiol diphosphate) 5mg or placebo to be taken three times per week. Participants are randomised in a 1:1 ratio to vitamin K4 or placebo by a computer-generated randomisation programme (generated by Sealed Envelope: https://sealedenvelope.com/) in random permuted blocks. The total duration of treatment and follow-up is 12 months for both vitamin K4 and placebo groups.

There are up to 5 visits to the hospital in this time, and up to two additional, brief meetings to hand out more study medication, like collecting a prescription.

They have transplant function and immunosuppression levels checked one month after starting to ensure the medication is not interfering with their renal transplant (this is not expected). Participants attend for a review - without any additional tests - at 6 months, when they are given more study medication. The final review takes place at 12 months when all the baseline tests are repeated.

Intervention type

Drug

Phase

Phase II

Drug names

Vitamin K4 (Menadiol diphosphate)

Primary outcome measure

Vascular stiffness is measured using the aortic distensibility on MRI scan at 12 months of treatment.

Secondary outcome measures

1. Carotid-femoral pulse wave velocity is measured using SphygmoCor XCEL PWA & PWV system at 12 months of treatment
2. Left ventricular mass, cardiac fibrosis, left atrial volume, global longitudinal strain, pulse wave velocity are measured using Cardiac MRI at 12 months of treatment
3. Marker of vitamin K status is measured using dp-ucMGP levels, Elastin degradation products (EDPs) at 12 months of treatment
4. Vascular health is measured using office (brachial) blood pressure, electrocardiogram (ECG), augmentation index measured by applanation tonometry at the radial artery at 12 months of treatment
5. Coronary and aortic calcification is measured using cardiac CT scan at 12 months of treatment
6. Bone metabolism and turnover measured using calcium, phosphate, parathyroid hormone, fibroblast growth factor-23 (FGF-23), 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, osteocalcin, fetuin, bone morphogenetic protein (BMP), Tartrate resistant acid phosphatase-5b (TRAP-5b) at 12 months of treatment
7. Cardiovascular markers are measured using high-sensitivity troponin and brain natriuretic peptide at 12 months of treatment
8. Endothelial function is measured using Asymmetric Dimethylarginine (ADMA) at 12 months of treatment
9. Dietary vitamin K content is estimated at baseline using 28-day food diary
10. Transplant function is measured using blood tests for urea and electrolytes at 12 months of treatment
11. Proteinuria is measured using urinary protein to creatinine ratio at 12 months of treatment
12. Quality of life is measured using the EQ-5D at 12 months of treatment

Overall trial start date

01/10/2016

Overall trial end date

18/08/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Male or female of non-child-bearing potential aged 18 years or over
2. Functioning renal transplant, transplanted > 12 months
3. eGFR >15ml/min by CKD-EPI equation

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

90

Participant exclusion criteria

1. Inability to give written informed consent
2. Atrial fibrillation
3. Taking warfarin (vitamin K antagonist)
4. Taking vitamin K or indication for vitamin K
5. Allergy or intolerance to gelatine, lactose or cellulose
6. Breast-feeding or women of child-bearing potential
7. Glucose-6-phosphate dehydrogenase (G6PD) deficiency
8. Life expectancy <12 months
9. Contraindications to MRI scan

Recruitment start date

26/09/2017

Recruitment end date

26/06/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Glasgow
Institute of Cardiovascular and Medical Sciences
Glasgow
G12 8TA
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde

Sponsor details

Research and Development Management Office
Clinical Research and Development Unit
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SW
United Kingdom

Sponsor type

Research organisation

Website

Funders

Funder type

Charity

Funder name

Kidney Research UK

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Darlinda's Charity for Renal Research

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

We intend to present results at an international renal conference (TBC) and publish in a high-impact journal in approximately November 2020. Protocol available upon request.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request after study results have been published. Specific data sharing plans to be confirmed and will be made available at a later date.

Intention to publish date

30/11/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

06/09/2018: The recruitment end date has been changed from 04/07/2018 to 26/06/2018