Oxidative stress in patients with chronic kidney disease

Plain English summary of protocol

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

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• Scotland
• United Kingdom

Study participating centre

Sponsor information

NHS Greater Glasgow and Clyde (UK)
Government

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

"ROR"	https://ror.org/05kdz4d87

Funders

Funder type

Charity

Results and Publications

Study outputs

Editorial Notes

22/01/2019: Publication reference added
26/01/2017: No publications found in PubMed, verifying study status with principal investigator.