Plain English Summary
Background and study aims
Chronic kidney disease is a long-term medical condition where the kidneys do work properly. It is a common disease, and particularly so in older people. Kidney problems affect the kidney, and also the health of blood vessels and the heart, leading to an increased risk of heart disease or strokes. Kidney problems lead to blood vessels becoming stiffer than usual, due to a build-up of calcium in the wall of the blood vessel. So finding ways to stop or reverse this stiffening of the blood vessels is really important, and we don’t have good treatments for this problem at the moment. 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. Before we can recommend this as a treatment though, it is important that giving extra vitamin K is tested properly in controlled trials such as this one.
Who can participate?
Patients with chronic kidney disease (stages 3b and 4 - so does not include those on dialysis)
What does the study involve?
Participants are randomly allocated into one of two groups. One group takes 400mcg of vitamin K once a day. The other group takes a placebo once a day. Each participant is asked to go to their study centre first for a screening visit, to see whether they are suitable for the study. They then visit the centre a further three times – at the start of the study, 6 months later and, finally, 12 months later. They undergo a number of tests during these visits including blood pressure measurements when lying down and when stood up, walking speed, strength and balance tests and an x-ray of their abdomen. Investigators also take samples of blood and ask participants to provide a urine sample. A small pencil-like device is also placed over the blood vessel of each participant to measure their pulse to test how stiff their blood vessels are. The electrical activity of their heart is also monitored with a heart tracing. At the end of each visit, participants are asked to take home a diary to record any falls they might have over the next six months. They are also given a blood pressure cuff to wear for the next 24 hours and a supply of the study medication they have been allocated to receive.
What are the possible benefits and risks of participating?
This dose of vitamin K has been used before and is known to be safe but as with all medications there is a small possibility of side effects. These can include sickness, diarrhoea and dizziness. Having blood taken can cause some bruising. The blood pressure cuff causes mild discomfort to some people. We allow participants to have plenty of rest in between the walking and strength tests so that they are not made overly tired by the tests.
Where is the study run from?
University of Dundee and the University of Glasgow, Scotland (UK)
When is the study starting and how long is it expected to run for?
June 2015 to August 2017
Who is funding the study?
The British Heart Foundation (UK)
Who is the main contact?
Dr Miles Witham
m.witham@dundee.ac.uk
Trial website
Contact information
Type
Public
Primary contact
Dr Miles Witham
ORCID ID
Contact details
Ninewells Hospital and Medical School
Ageing and Health Division of Medicine and Therapeutics
Ninewells Avenue
Dundee
DD1 9SY
United Kingdom
01382 383086
m.witham@dundee.ac.uk
Type
Scientific
Additional contact
Dr Miles Witham
ORCID ID
Contact details
Ninewells Hospital and Medical School
Ageing and Health Division of Medicine and Therapeutics
Ninewells Avenue
Dundee
DD1 9SY
United Kingdom
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
2014CV03
Study information
Scientific title
Vitamin K therapy to improve vascular health in patients with chronic kidney disease: a randomised controlled trial
Acronym
K4Kidneys
Study hypothesis
That 1 year of vitamin K2 supplementation (400mcg per day) improves pulse wave velocity compared to placebo in patients with CKD stages 3b and 4
Ethics approval
East of Scotland Research Ethics Committee, 16/06/2015, approval number: 15/ES/0085
Study design
Two-centre parallel-group placebo-controlled randomised trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format; please use contact details to request a patient information sheet
Condition
Chronic kidney disease stages 3b and 4
Intervention
400mcg once daily oral vitamin K2 (MK7 subtype) vs matching placebo
Intervention type
Supplement
Phase
Drug names
Primary outcome measures
Between-group difference in carotid-femoral pulse wave velocity (PWV) at 12 months using the Sphygmocor system
Secondary outcome measures
All measured at 0,6 and 12 months except for aortic radiography:
1. Vascular health:
1.1. Office and 24 hour blood pressure
1.2. B-type natriuretic peptide
1.3. Central systolic blood pressure and augmentation index derived from applanation tonometry at the radial artery using the Sphygmocor system.
1.4. Pulse wave velocity at 6 months (in addition to the primary outcome measured at 12 months)
2. Insulin and glucose levels to calculate insulin resistance using HOMA-IR
3. Marker of effect of vitamin K: dp-ucMGP levels.
4. Calcium and bone metabolism and turnover:
4.1. Osteocalcin
4.2. Tartrate resistant acid phosphatase-5b
4.3. Parathyroid hormone
4.4. Fetuin
4.5. Fibroblast growth factor-23
4.6. 25-hydroxyvitamin D
4.7. 1,25-hydroxyvitamin D
5. Renal function: We will measure serum creatinine, and urinary protein/creatinine ratio on a spot urine sample at each timepoint
6. Radiological calcification: We will perform lateral abdominal radiography at baseline and 12 months to assess aortic calcification.
7. Physical function:
7.1. Short physical performance battery
7.2 Grip strength at each timepoint
7.3. Monthly falls diary to prospectively record falls
Overall trial start date
01/06/2015
Overall trial end date
31/08/2017
Reason abandoned
Eligibility
Participant inclusion criteria
1. Age >18 years
2. CKD stages 3b or 4 (eGFR of >15 ml/min and <45 ml/min by MDRD4 equation)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
166
Participant exclusion criteria
1. Atrial fibrillation
2. Taking warfarin (which antagonises vitamin K) or other coumadin derivatives.
3. Taking vitamin K
4. Unable to give written informed consent
5. Currently enrolled in another trial, or within 30 days of completing another trial
6. Pregnant or (if female and pre-menopausal) not using reliable contraception
Recruitment start date
01/06/2015
Recruitment end date
31/05/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Ninewells Hospital and Medical School
Ageing and Health Division of Medicine and Therapeutics
Ninewells Avenue
Dundee
DD1 9SY
United Kingdom
Trial participating centre
University of Glasgow
Institute of Cardiovascular and Medical Sciences
Glasgow
G12 8TA
United Kingdom
Sponsor information
Organisation
Tayside Academic Science Centre (NHS Tayside and University of Dundee)
Sponsor details
TASC
Level 3
Ninewells Hospital
Dundee
DD1 9SY
United Kingdom
01382 383900
tasctayside@nhs.net
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
British Heart Foundation
Alternative name(s)
BHF
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
United Kingdom
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary