The effect of acidosis correction and exercise on tissue wasting and immune function in renal patients

ISRCTN ISRCTN34320210
DOI https://doi.org/10.1186/ISRCTN34320210
Secondary identifying numbers Version 4
Submission date
21/05/2008
Registration date
12/09/2008
Last edited
03/03/2015
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
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

Contact information

Prof John Feehally
Scientific

Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom

Email jf27@le.ac.uk

Study information

Study designRandomised controlled trial, factorial 2 x 2 design
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleThe effect of acidosis correction and exercise on tissue wasting and immune function in renal patients
Study objectives1. 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(s)Nottingham Research Ethics Committee 2, 27/11/2007, ref: 07/Q2404/16
Health condition(s) or problem(s) studiedChronic kidney disease
InterventionForty 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Sodium bicarbonate
Primary outcome measure1. 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 measures1. 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 study start date01/07/2007
Completion date01/09/2008

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants40
Key inclusion criteriaChronic kidney disease (CKD) patients at CKD stages 4 to 5
Key exclusion criteria1. Age less than 18 years, either sex
2. Pregnancy
3. Physical disability sufficient to preclude participating in an exercise programme
Date of first enrolment01/07/2007
Date of final enrolment01/09/2008

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Leicester General Hospital
Leicester
LE5 4PW
United Kingdom

Sponsor information

University Hospitals of Leicester NHS Trust (UK)
Hospital/treatment centre

c/o Professor DJ Rowbotham
Research & Development Director
Gwendolen Road
Leicester
LE5 4PW
England
United Kingdom

Email djr8@le.ac.uk
Website http://www.uhl-tr.nhs.uk/
ROR logo "ROR" https://ror.org/02fha3693

Funders

Funder type

Government

University Hospitals of Leicester NHS Trust (UK)

No information available

Kidney Research UK
Private sector organisation / Other non-profit organizations
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot expected to be made available
Publication and dissemination planTo 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.
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/03/2012 Yes No
Results article results 01/08/2013 Yes No
Results article results 01/09/2014 Yes No