Condition category
Nutritional, Metabolic, Endocrine
Date applied
06/03/2012
Date assigned
08/05/2012
Last edited
06/08/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Children with the genetic disease cystic fibrosis (CF) are prone to chest infection with a bacterium called Pseudomonas aeruginosa. Treatment with a type of antibiotic called an aminoglycoside can improve survival in these patients. However, exposure to these antibiotics can lead to reduced kidney function in around one third of patients by the time they’re adults. Currently we measure a substance called creatinine in blood tests to check how well the kidneys are working. However, creatinine is slow to respond to any damage to the kidney, so we may not find out that damage has occurred until it is too late to reverse it. A number of substances, called biomarkers, can be measured in the urine. We think that some of these biomarkers might be useful at telling us how well a child’s kidneys are working, and whether any damage is occurring as a result of treatment with aminoglycosides.

In this study we aim to measure these biomarkers in the urine of children with CF at regular intervals (routine outpatient clinic appointments), and during treatment with an aminoglycoside called tobramycin.

We expect that this research will help us to develop non-invasive urine biomarker tests which can identify kidney damage from aminoglycosides early. We aim to build upon this study to develop new methods of preventing kidney damage from this important group of antibiotics. Our ultimate aim is to improve the long-term outlook for children with CF by ensuring that far fewer develop kidney problems as a result of their treatment, and allow doctors to have access to the antibiotics they require to treat such patients. Ultimately we may be able to replace some uncomfortable blood tests with non-invasive urine tests, therefore reducing the burden on patients.

Who can participate?
Children and young adults with CF aged 0 to 20 years.

What does the study involve?
All participants will provide a urine sample on the day of recruitment (at a CF outpatient clinic) and each time they subsequently come to the clinic. Ideally the sample will be collected by asking the child to go into a toilet cubicle and pass urine into a sterile container. Parents may need to give their child some help with this. If the child is too young or not able to pass urine on demand, there are other ways we can collect the sample. None of these are invasive or painful, and these will be discussed with parents.
If the child has a course of intravenous tobramycin in hospital, or at home with daily community nurse visits, we will collect one urine sample on the same day but before the first dose of tobramycin, and a further urine sample each day during the treatment.
If the child has tobramycin at home without daily community nurse visits we will collect one urine sample on the same day but before the first dose of tobramycin, and a further urine sample on each day that monitoring blood tests are done, and on the final day of treatment.
We will provide parents with the sample pots required. We will also collect a follow-up sample 5-10 days after the last dose of tobramycin. We will arrange either to go and collect this sample, or for parents to bring it to the hospital.
Each child will be involved in the study for at least 1 year, and possibly up to 2 years.
We will store the urine samples in a freezer, and test for different biomarkers at different times. We will keep the sample until it is used up.

What are the possible benefits and risks of participating?
We do not anticipate any problems. We will choose an appropriate urine collection method for each child. There are no immediate benefits.

Where is the study run from?
University of Liverpool and Alder Hey Children’s NHS Foundation Trust

When is study starting and how long is it expected to run for?
The study is starting in April 2012 and is expected to run until October 2014

Who is funding the study?
Medical Research Council.

Who is the main contact?
Dr Steve McWilliam
S.Mcwilliam1@liverpool.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Stephen J McWilliam

ORCID ID

Contact details

University of Liverpool
Molecular and Clinical Pharmacology
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
S.Mcwilliam1@liverpool.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

11815

Study information

Scientific title

URinary Biomarkers of Aminoglycoside-induced Nephrotoxicity in children with Cystic Fibrosis

Acronym

URBAN CF

Study hypothesis

Children with the genetic disease cystic fibrosis (CF) are prone to chest infection with a resistant bacteria called Pseudomonas aeruginosa. Treatment with a type of antibiotic called an aminoglycoside, can improve survival in these patients. However, exposure to these antibiotics can cause reduced kidney function in around one third of patients by the time they’re adults. Currently we measure a substance called creatinine in blood tests to check how well the kidneys are working. However, creatinine is slow to respond to any damage to the kidney, so we may not find out that damage has occurred until it is too late to reverse it. A number of substances, called biomarkers, can be measured in the urine. We think that some of these biomarkers might be useful at telling us how well a child’s kidneys are working, and whether any damage is occurring as a result of treatment with aminoglycosides.

In this study we aim to measure these biomarkers in the urine of children with CF at regular intervals (routine outpatient clinic appointments), and during treatment with an aminoglycoside called tobramycin.

We expect that this research will help us to develop noninvasive urine biomarker tests which can identify kidney damage from aminoglycosides early. We aim to build upon this study to develop new methods of preventing kidney damage from this important group of antibiotics. Our ultimate aim is to improve the long term outlook for children with CF by ensuring that far fewer develop kidney problems as a result of their treatment, and allow doctors to have access to the antibiotics they require to treat such patients. Ultimately we may be able to replace some uncomfortable blood tests with noninvasive urine tests, therefore reducing the burden on patients.

More details can be found at http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=11815

Ethics approval

NRES Committee North West – Liverpool East, 27th February 2012, ref: 12/NW/0122

Study design

Observational clinical laboratory study

Primary study design

Observational

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Cystic fibrosis / kidney injury

Intervention

In this study children and young adults with CF will be asked to provide a number of urine samples. They will provide routine urine samples when they attend outpatient appointments, and they will also provide more frequent urine samples if they receive one or more courses of treatment with tobramycin.

Participants will be involved in the study for at least 1 year, and possibly up to 2 years. The urine samples will be analysed for a number of urine biomarkers. The primary aim of the study is to identify whether there are elevations in these urine biomarkers during treatment with tobramycin.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

The mean difference in urinary biomarker value between samples collected during tobramycin treatment, and samples collected when not receiving tobramycin. This will be calculated for each biomarker measured over the time course of each participants involvement in the study.

Secondary outcome measures

1. The association between urinary biomarker values and conventional measures of renal function [serum urea and creatinine, estimated glomerular filtration rate (eGFR)]
2. The association between urinary biomarker values and cumulative lifetime aminoglycoside exposure, compared to biomarker values in children with CF who have never received aminoglycosides and to a healthy children cohort
3. An analysis of changes in urinary biomarker values in the same patient with repeated courses of tobramycin

Overall trial start date

01/03/2012

Overall trial end date

01/10/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age 0-20 years, either sex (Some patients with CF will continue to be seen in a Paediatric CF clinic beyond the age of 16 and will therefore be included by having a higher upper age limit)
2. Diagnosis of cystic fibrosis (established by sweat test or genotype)

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

Planned Sample Size: 120; UK Sample Size: 120

Participant exclusion criteria

Does not meet inclusion criteria

Recruitment start date

01/03/2012

Recruitment end date

01/10/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Liverpool
Liverpool
L69 3GL
United Kingdom

Sponsor information

Organisation

University of Liverpool (UK)

Sponsor details

Whelan Building
Quadrangle
Brownlow Hill
Liverpool
L69 3GL
United Kingdom

Sponsor type

University/education

Website

http://www.liv.ac.uk/

Funders

Funder type

Research council

Funder name

Medical Research Council [MRC] (UK) ref: G1000417, 94909

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes