Screening test for Fabry disease in patients receiving haemodialysis in England
| ISRCTN | ISRCTN44751506 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN44751506 |
- Submission date
- 25/03/2021
- Registration date
- 26/05/2021
- Last edited
- 17/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Fabry disease is a rare (X-linked) genetic disorder that can affect many parts of the body including the kidneys and result in premature death. A recent large genetic screening study of newborns reported a higher incidence of Fabry disease in males, showing that Fabry disease is more frequent than previously expected. The diagnosis of Fabry disease is frequently delayed by around 14 years in males and 19 years in females. In the UK screening is not routinely done but is available in the forms of a dried blood spot test which measures enzyme activity. A female who has part of the Fabry genes (carriers) may have normal to low enzyme activity, so an additional blood test (plasma Lyso-GB3) and genetic testing are required. The aim of this study is to find out how many of the patients receiving haemodialysis in the West Midlands have Fabry disease, especially in those who are not known to have a cause of their kidney failure. This will also lead to further testing of relatives of identified patients (cascade screening), which in turn might help with an earlier diagnosis of Fabry disease and an earlier start of enzyme replacement treatment. Moreover, the identified patients in the haemodialysis population may benefit from enzyme replacement therapy for their heart disorders (i.e. coronary artery disease, cardiac failure and death).
Who can participate?
Patients receiving haemodialysis under the care of six kidney units in the Midlands in the UK
What does the study involve?
Participants' blood will be taken during routine dialysis session at a single timepoint. The blood will be dried on a card and sent for testing. In addition, participants will be asked to complete a questionnaire looking for any symptoms suggestive of Fabry disease. The study team will also collect participants’ relevant demographics and clinical data. The study will run for 12 months. All participants who test negative for Fabry disease will be notified by letter. No further visits or follow-up will be required unless the participant’s Fabry test is positive. The local kidney consultant involved in this study will inform the participants of the new diagnosis of Fabry disease and refer to the specialist Fabry disease clinic at the Queen Elizabeth Hospital in Birmingham. Any new cases of Fabry disease identified by the study will continue to receive specialist service at the Queen Elizabeth Hospital Birmingham as part of their routine NHS care. The specialist clinic will offer testing for family and relatives as the condition can be inherited. Treatment in the form of enzyme replacement is available and may be offered if deemed suitable.
What are the possible benefits and risks of participating?
All new cases of Fabry disease diagnosed during the study will be informed by their local kidney doctors. All cases will also be referred promptly for further counselling and review at the specialist Fabry Disease Clinic at the Queen Elizabeth Hospital Birmingham in order to support participants with the new diagnosis. All participants will also be offered further screening for their relatives. As blood samples are sampled on dialysis, participants will not have extra pain or discomfort. As Fabry disease is a genetic disorder, if participants are diagnosed to have Fabry disease during the study, it will have significant implications for participants' themselves as well as their relatives. Such clinical implications are fully explained in the Patient Information Sheet.
Where is the study run from?
University Hospitals Birmingham NHS Trust (UK)
When is the study starting and how long is it expected to run for?
February 2020 to December 2023
Who is funding the study?
Sanofi-Genzyme (USA)
Who is the main contact?
Prof. Indranil Dasgupta
indranil.dasgupta@uhb.nhs.uk
Contact information
Scientific
Birmingham Heartlands Hospital
Bordesley Green East
Birmingham
B9 5SS
United Kingdom
| Phone | +44 (0)121 424 2158 |
|---|---|
| indranil.dasgupta@uhb.nhs.uk |
Study information
| Study design | Cross-sectional epidemiological screening study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Epidemiological study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Screening for Fabry disease in the haemodialysis population |
| Study acronym | SoFAH |
| Study hypothesis | To estimate the prevalence of Fabry disease in a large haemodialysis population in the UK. |
| Ethics approval(s) | Approved 15/03/2022, East of England - Essex Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 2071048227; essex.rec@hra.nhs.uk), ref: 22/EE/0026 |
| Condition | Fabry disease |
| Intervention | All eligible patients are given a patient information sheet (PIS) and consent form by the research nurse during one of their haemodialysis sessions. All potential participants will be given the opportunity to ask questions regarding the study after receiving the PIS, following which the consent will be taken at the next dialysis session 24 to 72 hours later. Written informed consent is obtained by a research nurse prior to the participant undergoing procedures that are specifically for the purposes of the study. In the case of participants who cannot read or write or require translators, the study will allow a witness to sign on a participant’s behalf (in the case of problems with reading or writing), allow a witness to date the form on behalf of the participant and allow a hospital or personal interpreter. Participants' blood will be taken during routine dialysis session at a single timepoint. The blood will be dried on a card and sent for testing to the Archimed Laboratories in Vienna, Austria. In addition, participants will be asked to complete a questionnaire looking for any symptoms suggestive of Fabry disease. The study team will also collect participants’ relevant demographics and clinical data. The study will run for approximately 6 months. All participants who were tested negative for Fabry disease will be notified via letter. No further visits or follow-up will be required unless the participant’s Fabry test is positive. The local kidney consultant involved in this study will inform the participants of the new diagnosis of Fabry disease and refer them to the specialist Fabry disease clinic at the Queen Elizabeth Hospital in Birmingham. Any new cases of Fabry disease identified by the study will continue to receive specialist service at Queen Elizabeth Hospital Birmingham as part of their routine NHS care. The specialist clinic will offer testing for family and relatives as the condition can be inherited. Treatment in the form of enzyme replacement is available and may be offered if deemed suitable. |
| Intervention type | Other |
| Primary outcome measure | Prevalence of Fabry disease as defined by dried blood spot alfa-galactosidase A (GLA) enzyme activity, Lyso-Gb3 level and genetic mutation of GLA analysis at a single timepoint |
| Secondary outcome measures | 1. Clinical characteristics of new cases of Fabry disease identified by the study, including age, gender, ethnicity, duration of dialysis, cardiovascular history, previous renal diagnosis and previous renal biopsy report, measured using review of medical records at the time of study recruitment 2. Fabry disease symptoms measured using a questionnaire designed by the SoFAH study which consists of six questions at the time of study recruitment (single timepoint) 3. Quality of life measured using EQ5D-5L at the time of study recruitment (single timepoint) |
| Overall study start date | 01/02/2020 |
| Overall study end date | 31/12/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 2200 |
| Participant inclusion criteria | 1. Patients receiving haemodialysis under the care of the six participating renal units 2. Aged 18 years and above 3. Capable of giving informed consent |
| Participant exclusion criteria | Does not meet inclusion criteria |
| Recruitment start date | 04/08/2022 |
| Recruitment end date | 31/07/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Bordesley Green East
Birmingham
B9 5SS
United Kingdom
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
Coventry
CV2 2DX
United Kingdom
12, Corporate Services Centre
Wolverhampton
WV10 0QP
United Kingdom
Stoke-on-Trent
ST4 6QG
United Kingdom
Shrewsbury
SY3 8XQ
United Kingdom
Pensnett Rd
Dudley
DY1 2HQ
United Kingdom
Sponsor information
Hospital/treatment centre
Queen Elizabeth Hospital Birmingham
Mindelsohn Way
Birmingham
B15 2TH
England
United Kingdom
| Phone | +44 (0)1213713702 |
|---|---|
| joanne.plumb@uhb.nhs.uk | |
| Website | http://www.uhb.nhs.uk/ |
"ROR" |
https://ror.org/014ja3n03 |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Genzyme Corporation, Genzyme Corp.
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The findings of this study will be reported at appropriate conferences and the aim is to publish them in a relevant open access journal. A summary report will be produced adherent to the funder’s guidelines at the completion of the project. Participants in the study will also be informed of the study outcome via a letter. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Indranil Dasgupta (Indranil.dasgupta@uhb.nhs.uk). Anonymised patient-level data will be available after the publication of the primary paper of the study for up to 5 years. A data-sharing agreement with the sponsor trust will be required. Data will be shared with researchers interested in this area. As this is an industry-funded study, the data will also be shared with the funders. Consent will be obtained along with the consent for the study. Data will be pseudoanonymised. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version V1.0 | 18/02/2021 | 26/05/2021 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Preprint results | version 1.5 | 25/03/2025 | 17/04/2025 | No | No |
| Protocol file | version 1.3 | 27/09/2022 | 17/04/2025 | No | No |
Additional files
Editorial Notes
17/04/2025: The following changes were made to the trial record:
1. A file of preprint results was uploaded.
2. Uploaded protocol v1.3 (not peer-reviewed) as an additional file.
28/02/2025: A contact email was updated.
15/12/2022: The following changes were made to the trial record:
1. The recruitment end date has been changed from 02/12/2022 to 31/07/2023.
2. The overall trial end date has been changed from 03/08/2023 to 31/12/2023 and the plain English summary was updated to reflect that change.
3. The intention to publish date has been changed from 02/06/2023 to 31/12/2024.
31/08/2022: The following changes were made to the trial record:
1. The ethics approval was added.
2. The overall end date was changed from 03/01/2023 to 03/08/2023.
3. The recruitment start date was changed from 08/08/2022 to 04/08/2022.
4. The plain English summary was updated to reflect these changes.
19/07/2022: The recruitment start date has been changed from 04/07/2022 to 08/08/2022.
23/06/2022: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/06/2021 to 04/07/2022.
2. The recruitment end date was changed from 01/06/2022 to 02/12/2022.
3. The overall end date was changed from 01/06/2022 to 03/01/2023.
4. The intention to publish date was changed from 01/12/2022 to 02/06/2023.
5. The plain English summary was updated to reflect these changes.
26/05/2021: Uploaded protocol Version 1.0, 18 February 2021 (not peer reviewed).
31/03/2021: Trial's existence confirmed by Sanofi.
