Plain English Summary
Background and study aims
Patients with Chronic Kidney Disease (CKD) very often find that their muscles get smaller and weaker, especially the muscles in their legs. These patients will often have other health problems as well as their kidney disease and will suffer regular infections, which is a major cause of death in this patient group. This suggests that muscle loss is linked to a defect in the immune system. A problem that is seen in nearly all patients is that acid accumulates in the blood and tissues (acidosis) and research suggests that this acidosis may cause muscle loss and a problem with the immune system. We know that regular exercise helps maintain a healthy muscle mass and a strong immune system, but we do not know if this is the case in CKD patients. The aim of this study is to test the ability of two treatments, sodium bicarbonate (an alkali therapy to correct the acidosis) and regular exercise, to improve the immune system and prevent muscle loss. Furthermore, we will determine if these treatments work best when given alone, or in combination with each other.
Who can participate?
Chronic kidney disease (CKD) patients at CKD stages 4 to 5.
What does the study involve?
The study involves a series of tests performed before and after a 6-month period to see the effect the alkali therapy and exercise has had on the immune system and the patient’s ability to put on muscle. These tests include:
1. A skeletal muscle biopsy – this involves taking a small amount of muscle from your leg using a needle
2. Blood and urine samples
3. An exercise test on a treadmill
4. A DEXA scan (dual-energy x-ray absorbance)
5. Questionnaires about how you feel about your health
6. A food diary
We will then put you into one of four groups at random:
1. Exercise + sodium bicarbonate + usual care
2. Exercise + usual care
3. Sodium bicarbonate + usual care
4. Usual care only
If you are in the exercise group we will then ask you to start a 6-month regular walking programme. We will design the programme for you based upon how you did in the treadmill exercise test. We will ask you to aim for walking 5 days a week for 30 minutes, but it is likely that we will build up to this gradually. We will see you once a month to update your programme and discuss your progress. We will also ask you to fill in an exercise diary so we can see what you are doing. At the end of the 6 months we will repeat all the tests we did at the beginning, including the muscle biopsy to see if anything has changed.
What are the possible benefits and risks of participating?
There are no direct benefits to you of taking part in this research, although we anticipate that participating in the exercise training sessions will help you to improve your physical fitness levels. We hope that the results of the study will help us design improved treatments for other kidney patients in the future. There are no reported serious problems associated with a muscle biopsy and there is a very low risk of bleeding or infection at the site of the biopsy. You will first be given an injection of local anaesthetic which may cause slight discomfort. The biopsy itself is not painful, but the area may ache for a while afterwards (you will be offered painkillers to take away if you need them). You will need to refrain from eating or drinking anything other than water until you have completed the test. Therefore you may be rather hungry, but we will arrange these tests for the morning to reduce the time before you can eat. As with all exercise there is a small risk of injury especially when using a treadmill. However, you will be supervised at all times by trained staff to help minimise this risk. Committing to a research study such as this means you will need to give up some of your time. We cannot pay you for this time, but we can reimburse you for any travel-related costs for attending study appointments.
Where is the study run from?
Leicester General Hospital (UK).
When is the study starting and how long is it expected to run for?
From July 2007 to August 2008.
Who is funding the study?
University Hospitals of Leicester NHS Trust and Kidney Research UK.
Who is the main contact?
Prof John Feehally
jf27@le.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof John Feehally
ORCID ID
Contact details
Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom
-
jf27@le.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Version 4
Study information
Scientific title
The effect of acidosis correction and exercise on tissue wasting and immune function in renal patients
Acronym
Study hypothesis
1. That efficient correction of blood acidity by feeding extra alkali to the patients improves their exercise tolerance, reduces muscle wasting, and improves the functioning of their immune system
2. That exercise therapy improves their exercise tolerance, reduces muscle wasting, and improves the functioning of their immune system
3. That applying alkali therapy and exercise therapy together exerts beneficial effects greater than with either therapy alone
Ethics approval
Nottingham Research Ethics Committee 2, 27/11/2007, ref: 07/Q2404/16
Study design
Randomised controlled trial, factorial 2 x 2 design
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 the contact details below to request a patient information sheet
Condition
Chronic kidney disease
Intervention
Forty patients will be assigned randomly to the following four groups to determine whether alkali and exercise together are more effective than alkali or exercise alone:
1. Standard clinical therapy only (no exercise and target plasma bicarbonate of 24 mmol/L)
2. Additional alkali therapy (no exercise and target plasma bicarbonate of 29 mmol/L)
3. Exercise therapy without additional alkali therapy (target plasma bicarbonate of 24 mmol/L)
4. Exercise therapy and additional alkali therapy (target plasma bicarbonate of 29 mmol/L)
Intervention type
Drug
Phase
Not Applicable
Drug names
Sodium bicarbonate
Primary outcome measure
1. Changes in immune function - in vitro assessment of lymphocyte proliferation and neutrophil activation
2. Changes in body composition - dual energy X-ray absorptiometry (DEXA) scanning
Measurements made at zero and 6 months (end of study).
Secondary outcome measures
1. Changes in exercise tolerance - submaximal exercise testing (bicycle ergometry or treadmill exercise) to determine maximal oxygen uptake and lactate threshold
2. Muscle biopsies - in vitro evaluation of intracellular signalling pathways that regulate protein synthesis
3. Changes in cardiovascular function - blood pressure, pulse wave velocity, finometry
4. Changes in quality of life measures - Leicester Uraemic Symptoms Score
Measurements made at zero and 6 months (end of study).
Overall trial start date
01/07/2007
Overall trial end date
01/09/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Chronic kidney disease (CKD) patients at CKD stages 4 to 5
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40
Participant exclusion criteria
1. Age less than 18 years, either sex
2. Pregnancy
3. Physical disability sufficient to preclude participating in an exercise programme
Recruitment start date
01/07/2007
Recruitment end date
01/09/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Leicester General Hospital
Leicester
LE5 4PW
United Kingdom
Sponsor information
Organisation
University Hospitals of Leicester NHS Trust (UK)
Sponsor details
c/o Professor DJ Rowbotham
Research & Development Director
Gwendolen Road
Leicester
LE5 4PW
United Kingdom
-
djr8@le.ac.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
University Hospitals of Leicester NHS Trust (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Kidney Research UK
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
United Kingdom
Results and Publications
Publication and dissemination plan
To date we have published three papers from this study (see below). We have also presented several abstracts at both national and international conferences. Sample analysis is ongoing and more papers will be published this coming year.
Intention to publish date
Participant level data
Not expected to be available
Basic results (scientific)
Publication list
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/21795756
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23591985
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24700875