Condition category
Urological and Genital Diseases
Date applied
30/11/2015
Date assigned
10/02/2016
Last edited
13/07/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Dr Alice Smith

ORCID ID

http://orcid.org/0000-0002-9234-9060

Contact details

Leicester Kidney Exercise Team
University of Leicester Academic Unit
Leicester General Hospital
Leicester
LE5 5PW
United Kingdom
+44 (0)1162 584346
aa50@le.ac.uk

Type

Scientific

Additional contact

Dr Emma Watson

ORCID ID

http://orcid.org/0000-0002-3869-8972

Contact details

Lab 117/119 MSB
University Road
University of Leicester
Leicester
LE1 9HN
United Kingdom
+44 (0)1162 525033
ec174@le.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Mechanisms of muscle wasting in advanced chronic kidney disease

Acronym

Explore CKD

Study hypothesis

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

NHS East Midlands - Leicester South Research Ethics Committee, 28/11/2015, ref: 15/EM/0467

Study design

Mechanistic observational laboratory-based study

Primary study design

Observational

Secondary study design

Mechanistic observational laboratory-based study

Trial setting

Hospitals

Trial type

Other

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

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

Phase

Drug names

Primary outcome measures

Muscle fibre size is measured using immunohistochemistry.

Secondary outcome measures

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

Overall trial start date

01/01/2016

Overall trial end date

02/11/2020

Reason abandoned

Eligibility

Participant 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

Participant type

Mixed

Age group

Adult

Gender

Both

Target number of participants

7

Participant 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.

Recruitment start date

01/01/2015

Recruitment end date

02/11/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom

Sponsor information

Organisation

University Hospitals of Leicester (UK)

Sponsor details

R&I Office
Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Kidney Research UK

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication of study results in a peer reviewed journal as well as presentation at national and international conferences.

Intention to publish date

31/12/2016

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes