An investigation into why people with kidney disease lose muscle and feel weak
| ISRCTN | ISRCTN18221837 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18221837 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 187619 |
| Protocol serial number | Nil known |
| Sponsor | University Hospitals of Leicester (UK) |
| Funder | Kidney Research UK |
- Submission date
- 30/11/2015
- Registration date
- 10/02/2016
- Last edited
- 18/09/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
Background and study aims
Chronic kidney disease (CKD) is a long-term condition where the kidneys do not work properly. In a healthy person, the kidneys are vital for filtering out the waste products and excess water in the blood, and converting them into urine. In patients suffering from CKD, the kidneys are unable to do this, and so the body is unable to get rid of the waste products building up in the blood. A common feature of CKD is muscle wasting (when the muscles waste away). This can start early on in the disease, and is thought to play an important role in the way the disease progresses, and even the patients’ ultimate chance of survival. It inevitably leads to a poor quality of life and an inactive (sedentary) lifestyle, which in itself can be bad for general health. Currently, the exact cause of muscle wasting in CKD is not really known, and so further research is needed so that it can be better understood and treated. The aim of this study is to grow small pieces of muscle taken from the legs of adult CKD sufferers and healthy adults in the laboratory, in order to find out what is different in the muscle of CKD patients and what the cause of their muscle loss may be. These muscles will also be stretched in the lab to simulate exercise, in order to find out if exercise could have any positive effects.
Who can participate?
Adults suffering from severe CKD and healthy adults of the same age, sex and race.
What does the study involve?
All participants have a small sample of muscle tissue taken from their thigh (biopsy) using a needle. They also provide a blood sample and a urine sample at this time. Information about their condition is gathered using a questionnaire at the start of the study, and then again at 6, 12 and 24 months.
What are the possible benefits and risks of participating?
There are no direct benefits for participants taking part in this study. The muscle biopsy carries with it a small risk of bleeding and infection, but to minimise these risks participants taking blood thinners are not able to take part and the procedure will be performed under sterile conditions. The area will ache for a day or so afterwards.
Where is the study run from?
Leicester General Hospital (UK)
When is the study starting and how long is it expected to run for?
March 2015 to May 2016
Who is funding the study?
Kidney Research UK (UK)
Who is the main contact?
1. Dr Alice Smith (Scientific)
aa50@le.ac.uk
2. Dr Emma Watson (Scientific)
ec174@le.ac.uk
Contact information
Scientific
Leicester Kidney Exercise Team
University of Leicester Academic Unit
Leicester General Hospital
Leicester
LE5 5PW
United Kingdom
 ORCID ID |
0000-0002-9234-9060 |
|---|---|
| Phone | +44 (0)1162 584346 |
| aa50@le.ac.uk |
Scientific
Lab 117/119 MSB
University Road
University of Leicester
Leicester
LE1 9HN
United Kingdom
| ORCID ID |
0000-0002-3869-8972 |
|---|---|
| Phone | +44 (0)1162 525033 |
| ec174@le.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Mechanistic observational laboratory-based study |
| Secondary study design | Mechanistic observational laboratory-based study |
| Study type | Participant information sheet |
| Scientific title | Mechanisms of muscle wasting in advanced chronic kidney disease |
| Study acronym | Explore CKD |
| Study objectives | The aim of this study is to investigate the mechanisms of muscle wasting in human CKD and their potential to be manipulated by exercise. Main research questions: 1. How is the molecular control of muscle protein synthesis and degradation modified in CKD and affected by exercise? 2. How is the process of myogenesis modified in CKD and affected by exercise? 3. Is there a molecular role of microRNA in muscle loss in CKD? |
| Ethics approval(s) | NHS East Midlands - Leicester South Research Ethics Committee, 28/11/2015, ref: 15/EM/0467 |
| Health condition(s) or problem(s) studied | Chronic kidney disease |
| Intervention | A one-off muscle sample will be collected from the leg of CKD patients and matched controls as well as a blood and urine sample. These samples will be used in laboratory experiments to understand the mechanisms of muscle loss in this disease. We will also collect clinical information at 6, 12 and 24 months. |
| Intervention type | Other |
| Primary outcome measure(s) | Muscle fibre size is measured using immunohistochemistry. |
| Key secondary outcome measure(s) | 1. Differences in the processes of myogenesis measured using flow cytometry, immunohistochemistry and PCR 2. Differences in protein turnover measured using uptake and release labelling experiments 3. MicroRNA expression and involvement in any dysregulation seen above measured using next generation sequencing and PCR 4. Amino acid transport and intracellular concentrations 5. Muscle architecture 6. Metabolic flexibility and mitochondrial function measured using high resolution respirometry at baseline, 6, 12 and 24 months 7. Differences in physical activity levels between groups determined using patient questionnaires at baseline, 6, 12 and 24 months |
| Completion date | 02/11/2020 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 7 |
| Total final enrolment | 73 |
| Key inclusion criteria | CKD patients: 1. Over 18 years of age 2. Diagnosed CKD stage 3b-5 3. If diabetic, good control - HbA1c <9% Matched controls - will be matched to CKD patients for age, sex and race. 1. Over 18 years of age 2. Kidney function < 80mL/min/1.73m2 3. Good general health |
| Key exclusion criteria | CKD patients: 1. Aged under 18 years 2. Uncontrolled diabetes mellitus (HbA1c >9%) 3. Inability to give consent for any reason Matched controls: 1. Aged under 18 years 2. Presence of CKD (eGFR>80mL/min/1.73m2) 3. Presence of other diseases known to cause muscle wasting (some cancers, sepsis, burns and HIV) 4. Inability to give informed consent for any reason. |
| Date of first enrolment | 01/01/2015 |
| Date of final enrolment | 02/11/2020 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Leicester
LE5 4PW
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 25/04/2022 | 18/09/2023 | Yes | No | |
| Results article | 06/12/2019 | 18/09/2023 | Yes | No | |
| Results article | 14/01/2022 | 18/09/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Plain English results | 18/09/2023 | 18/09/2023 | No | Yes |
Additional files
Editorial Notes
18/09/2023: Publication references, IRAS number, plain English results and total final enrolment added.
