Vitamin K therapy to improve vascular health in patients with chronic kidney disease

ISRCTN ISRCTN21444964
DOI https://doi.org/10.1186/ISRCTN21444964
Secondary identifying numbers 2014CV03
Submission date
12/02/2015
Registration date
24/02/2015
Last edited
24/08/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Urological and Genital Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

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

Contact information

Dr Miles Witham
Public

Ninewells Hospital and Medical School
Ageing and Health Division of Medicine and Therapeutics
Ninewells Avenue
Dundee
DD1 9SY
United Kingdom

Phone 01382 383086
Email Miles.Witham@newcastle.ac.uk
Dr Miles Witham
Scientific

Ninewells Hospital and Medical School
Ageing and Health Division of Medicine and Therapeutics
Ninewells Avenue
Dundee
DD1 9SY
United Kingdom

Study information

Study designTwo-centre parallel-group placebo-controlled randomised trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Other
Study typeTreatment
Participant information sheet Not available in web format; please use contact details to request a patient information sheet
Scientific titleVitamin K therapy to improve vascular health in patients with chronic kidney disease: a randomised controlled trial
Study acronymK4Kidneys
Study objectivesThat 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(s)East of Scotland Research Ethics Committee, 16/06/2015, approval number: 15/ES/0085
Health condition(s) or problem(s) studiedChronic kidney disease stages 3b and 4
Intervention400 mcg once daily oral vitamin K2 (MK7 subtype) vs matching placebo
Intervention typeSupplement
Primary outcome measureBetween-group difference in carotid-femoral pulse wave velocity (PWV) at 12 months using the Sphygmocor system
Secondary outcome measuresAll 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 study start date01/06/2015
Completion date31/03/2019

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants166
Total final enrolment159
Key inclusion criteria1. Age >18 years
2. CKD stages 3b or 4 (eGFR of >15 ml/min and <45 ml/min by MDRD4 equation)
Key exclusion criteria1. 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
Date of first enrolment01/06/2015
Date of final enrolment31/05/2016

Locations

Countries of recruitment

  • Scotland
  • United Kingdom

Study participating centres

Ninewells Hospital and Medical School
Ageing and Health Division of Medicine and Therapeutics
Ninewells Avenue
Dundee
DD1 9SY
United Kingdom
University of Glasgow
Institute of Cardiovascular and Medical Sciences
Glasgow
G12 8TA
United Kingdom

Sponsor information

Tayside Academic Science Centre (NHS Tayside and University of Dundee)
University/education

TASC, Level 3, Ninewells Hospital
Dundee
DD1 9SY
Scotland
United Kingdom

Phone 01382 383900
Email tasctayside@nhs.net
Website http://www.ahspartnership.org.uk/
ROR logo "ROR" https://ror.org/049x86d03

Funders

Funder type

Research organisation

British Heart Foundation
Private sector organisation / Trusts, charities, foundations (both public and private)
Alternative name(s)
the_bhf, The British Heart Foundation, BHF
Location
United Kingdom

Results and Publications

Intention to publish date30/09/2019
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planTo be confirmed at a later date
IPD sharing planThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Anonymised, individual-participant data from the current study will be available to bona-fide researchers upon request from Professor Miles Witham (Miles.Witham@newcastle.ac.uk), subject to submission of a data access request outlining the planned analysis, purpose of the analysis, data required and publication plan, and subject to approval by the Sponsor

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Basic results 27/09/2019 27/09/2019 No No
Results article results 01/10/2020 24/08/2020 Yes No
HRA research summary 28/06/2023 No No

Additional files

ISRCTN21444964_BasicResults_27Sep19.pdf
Uploaded 27/09/2019

Editorial Notes

24/08/2020: Publication reference and total final enrolment number added.
30/09/2019: The IPD sharing statement was added to the publication and dissemination plan.
27/09/2019: The basic results of this trial have been uploaded as an additional file.
17/06/2019: An intention to publish date has been added.
10/06/2019: Dr Miles Witham's email address has been updated.
03/09/2018: The overall trial end date was updated from 31/08/2017 to 31/03/2019.
05/04/2016: Ethics approval information added.