Condition category
Urological and Genital Diseases
Date applied
29/10/2013
Date assigned
18/12/2013
Last edited
18/12/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
We already know that the blood vessels in patients with chronic kidney disease (CKD) do not function properly, and that this can contribute to a higher blood pressure and to stiffer blood vessels. It has been suggested that increased “oxidative stress” is an important cause for the impaired function of blood vessels in CKD, but this has not been studied in detail. In this context, “oxidative stress” means an increased production of highly reactive oxygen molecules that have the potential to impair the function of blood vessels. In this research project, we are investigating whether infusing the antioxidant vitamin C, which can reduce oxidative stress, improves blood vessel function in CKD patients and in a group of healthy volunteers. In future this knowledge could lead to therapies that improve blood vessel function and reduce blood pressure in CKD patients.

Who can participate?
People with chronic kidney disease stages 3 – 5, people with chronic kidney disease requiring dialysis, and people with hypertension and normal kidney function.

What does the study involve?
Study visit 1 will be during one of your regular visits to the renal clinic. We will check whether you are eligible for this study, give you information about the study and take some blood and urine samples. Visit 2 will be at the Clinical Research Facility for the actual test of blood vessel function, including the intravenous infusion of vitamin C.
On each occasion, we ask you to come fasted (from midnight for a morning appointment and after breakfast for an afternoon appointment) and not to take any caffeine for 12 hours beforehand.
Visit 1
After you have read the project information sheet, we will answer any questions that you might have about this study. This will take about 15 minutes.
We will perform a brief clinical examination, measure height and weight and ask you some simple questions about your health and the medication you are taking.
We will measure your blood pressure using a machine (similar to the one used at the renal clinic and at the GP practice). Clinical examination and blood pressure measurement should take no longer than 15 minutes.
We will also look at the results of the blood and urine taken at your renal clinic appointments (no additional samples are required for visit 1).
Visit 2
We will put two cannulas in the veins of your arms, one for infusions and one for drawing bloods.
We will first infuse normal saline over duration of 10 minutes. We will wait 10 minutes and then take a blood sample (about 15 ml, about two teaspoonfuls). The blood will be stored in our lab to be analysed at a later date, to look at markers of oxidative stress.
We will then examine the blood vessels in your wrist. This examination involves assessment of your pulse with a pencil-like probe. It is carried out at the artery in your wrist and enables us to look at the pulse waveform, which gives us useful information about the blood vessels. This will take about 15 minutes.
We will then measure changes in the diameter of your main artery of your arm with an ultrasound probe. We will apply a jelly-like substance to the skin and the probe will be gently pressed against your upper arm to visualise the main artery. A blood pressure cuff will be placed around your forearm and inflated for 5 minutes. We can then measure the changes in the diameter of the upper arm artery after deflation of the blood pressure cuff. The final part of the test involves a spray of a medication called GTN spray under the tongue. GTN is a very short acting medication which dilates the blood vessel. Overall, this will take about 20 minutes.
We will then infuse vitamin C at a dose of 2 grams over 10 minutes. Subsequently, we will take another blood sample (about 15 ml, about two teaspoons), and repeat the examinations of the blood vessels in your wrist and arm, as described above. We will then take a third blood sample (about 15 ml, about two teaspoons).
The total time for these tests will be about 160 minutes (60 minutes for the infusions and 70 minutes for the above described tests of blood vessel function, 30 minutes to take consent, assess basic parameters, and move you through the study process).

What are the possible benefits and risks of participating?
We will take blood from the vein in your arm which in rare cases results in a small bruise. The amount of blood taken for this research does not place you at any risk. The other tests are ‘non-invasive’ – the probes are attached to the skin and no needles are involved. Assessment of the pulse waveform has no specific side effects or risks. Inflation of the blood pressure cuff during the examination of your main arm artery may lead to some discomfort and numbness in the fingers. This will disappear when the cuff is deflated. A small bruise on your forearm may result from the cuff but will disappear within a couple of days. Some studies have suggested that administration of vitamin C may cause kidney stones. To minimize any such risk, you should not take part in this study if you previously had a kidney stone or if you are already taking daily vitamin C supplements. GTN spray is very short acting. In some people it can cause a headache which is short lived and will disappear within a few minutes.

Where is the study run from?
The British Heart Foundation Glasgow Clinical Research Centre (UK)

When is study starting and how long is it expected to run for?
February 2012 – February 2015

Who is funding the study?
NHS Greater Glasgow and Clyde Renal Unit Endowment Fund (UK)

Who is the main contact?
Dr Keith Gillis, Clinical Research Fellow
keithgillis@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Dr Patrick Mark

ORCID ID

Contact details

BHF GCRC
126 University Place
Glasgow
G12 8TA
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

GN11RE311

Study information

Scientific title

Oxidative stress in patients with chronic kidney disease: a cross over study of vitamin C versus normal saline

Acronym

Renox

Study hypothesis

Vitamin C will improve endothelial function and markers of oxidative stress in patients with chronic kidney disease.

Ethics approval

West of Scotland Research Ethics Service; 15th May 2012; 11/WS/0045

Study design

Single centre, non-randomised, cross over study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Renal Chronic kidney disease, Cardiovascular disease

Intervention

Ascorbic acid 2000mg in 100ml 0.9% saline given intravenously by peripheral cannula over 10 minutes. There is no randomisation and follow up is for the duration of the study visit, that is around 1.5 hours.

Intervention type

Supplement

Phase

Not Applicable

Drug names

Vitamin C

Primary outcome measures

Change in flow mediated dilatation assessed by brachial artery ultrasound, after saline and after ascorbic acid

Secondary outcome measures

1. Arterial stiffness assessed by pulse wave analysis using the Sphygmocor system.
2. Biomarkers of oxidative stress both measured after saline and then at 0 and 60 minutes after ascorbic acid:
2.1 Total antioxidant capacity measured by colorimetric assay
2.2 Rate of reactive oxygen species generation measured by electron paramagnetic resonance

Overall trial start date

21/05/2012

Overall trial end date

01/02/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged over 18 years
2. Written informed consent
3. CKD - patients with chronic kidney disease recruited from local clinic. eGFR 15 - 30ml/min on recent bloods.
4. ESRD - patients with end stage renal disease recruited from local service. Currently receiving renal replacement therapy
5. HTN - patients with hypertension recruited from local clinic. Normal renal function but diagnosis of hypertension

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

1. Known liver disease (alcoholic liver disease, hepatitis, cirrhosis)
2. Known HIV infection
3. Known i.v. drug or alcohol abuse
4. Clinical signs of acute infection
5. Known pregnancy
6. Women of childbearing age are who are at risk of pregnancy
7. Subjects with a history of kidney stones
8. Subjects taking daily vitamin C supplements

Recruitment start date

21/05/2012

Recruitment end date

01/02/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

BHF GCRC
Glasgow
G12 8TA
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde (UK)

Sponsor details

c/o Dr Maureen Travers
R&D Management Office
Western Infirmary
Tennent Institute
1st floor 38 Church Street
Glasgow
G11 6NT
United Kingdom

Sponsor type

Government

Website

Funders

Funder type

Charity

Funder name

NHS Greater Glasgow and Clyde Renal Unit Endowment Fund (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes