Relation between enzyme replacement therapy and progression of brain lesions in Fabry disease

ISRCTN	ISRCTN14072182
DOI	https://doi.org/10.1186/ISRCTN14072182
ClinicalTrials.gov number	NCT00196742

Submission date: 27/01/2015
Registration date: 10/02/2015
Last edited: 21/06/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Fabry disease is an inherited disorder that results from the build-up of a particular type of fat (globotriaosylceramide) in the body's cells. Beginning in childhood, this build-up causes signs and symptoms that affect many parts of the body including the brain. In the brain, small groups of dead cells clump together in the white matter and are known as white-matter lesions. These lesions may lead to a high risk of early dementia, stroke or death. Little is known about the development of white-matter lesions and how they relate to other factors (e.g., age, sex or smoking) or how they are affected by treatment of Fabry disease with ERT. Salford Royal NHS Foundation Trust (UK) has a database of patients with Fabry disease in the northwest of England. The aim in this study is to look in detail at the relation between ERT and progression of brain lesions in Fabry disease so as to understand how the incidence and burden of the lesions change over time.

Who can participate?
Adults with Fabry disease who have had two MRI scans, 1 year apart

What does the study involve?
The size of the white-matter lesions will be measured over time and this information will be used alongside details of age, sex, risk factors for stroke/heart disease and treatment with ERT.

What are the possible benefits and risks of participating?
There are no known benefits or risks to participants taking part in this study

Where is the study run from?
Salford Royal NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
February 2015 to December 2015

Who is funding the study?
Investigator initiated and funded (UK)

Who is the main contact?
Mrs Sharon Hulme
sharon.hulme@manchester.ac.uk

Contact information

Mrs Sharon Hulme
Public

Salford Royal NHS Foundation Trust
Clinical Sciences Building
Stott Lane
Salford
M6 8HD
United Kingdom

Phone	+44 0161 206 5755
Email	sharon.hulme@manchester.ac.uk

Dr Craig Smith
Scientific

Salford Royal NHS Foundation Trust
Clinical Sciences Building
Stott Lane
Salford
M6 8HD
United Kingdom

Phone	+440161 206 0623
Email	craig.smith-2@manchester.ac.uk

Study information

Study design	Observational study
Primary study design	Observational
Secondary study design
Study setting(s)	Hospital
Study type	Other
Scientific title	Magnetic resonance imaging of effect of enzyme replacement therapy on progression of cerebral white-matter lesions in Fabry disease: an observational study
Study objectives	1. Does treatment of Fabry disease with enzyme replacement therapy (ERT) affect the build up and progression of white matter lesions? 2. White matter lesions can increase the risk of stroke and dementia and it is important to assess if treatment with ERT increases this risk
Ethics approval(s)	NRES Committee West Midlands - South Birmingham, 19/02/2015, ref: 15/WM/0064
Health condition(s) or problem(s) studied	Fabry disease
Intervention	Retrospective analysis of a database and serial magnetic resonance imaging (MRI) scans to assess: 1. Progression of white matter lesions in patients with Fabry disease 2. Relation between disease progression and treatment with ERT
Intervention type	Biological/Vaccine
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)
Primary outcome measure	Prevalence and burden of white matter lesions over time: MRI scans at baseline and at 2 years will be compared for evidence of white-matter lesions using a visual severity rating scale
Secondary outcome measures	Progression of white matter lesions: MRI scans at baseline and at 2 years will be compared for evidence of white-matter lesions using a visual severity rating scale
Overall study start date	15/02/2015
Completion date	31/12/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	100 data records
Total final enrolment	149
Key inclusion criteria	1. Confirmed diagnosis of Fabry disease 2. Age at least 18 years old 3. Being followed up at Salford Royal NHS Foundation Trust (UK) 4. Registered in Fabry disease registry 5. At least two serial MRI brain scans (1 year apart)
Key exclusion criteria	1. New patient 2. No serial MRI scans 3. MRI scans of insufficient quality for analysis
Date of first enrolment	15/02/2015
Date of final enrolment	31/12/2015

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Salford Royal NHS Foundation Trust

Clinical Sciences Building
Stott lane
Salford
M6 8HD
United Kingdom

Sponsor information

University of Manchester
University/education

Room 3.53 Simon Building
Oxford Road
Manchester
M13 9PL
England
United Kingdom

"ROR"	https://ror.org/027m9bs27

Funders

Funder type

Not defined

Investigator initiated and funded (UK)

No information available

Results and Publications

Intention to publish date	31/12/2018
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Ana Jovanovic Ana.Jovanovic@srft.nhs.uk

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	09/10/2018	14/06/2019	Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

21/06/2019: ClinicalTrials.gov number added.
14/06/2019: Publication reference and total final enrolment number added.
26/01/2018: The basic results of this trial have been uploaded as an additional file.
07/12/2016: The overall trial end date has been updated from 31/12/2015 to 31/12/2016.
04/04/2016: Ethics approval information added.