Early diagnosis of Stickler syndrome using a screening tool in children with Perthes disease
| ISRCTN | ISRCTN86229394 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN86229394 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 343181 |
| Protocol serial number | Nil known |
| Sponsor | Cambridge University Hospitals NHS Foundation Trust and University of Cambridge |
| Funders | Addenbrooke's Charitable Trust, Cambridge University Hospitals, Cambridge Commonwealth European and International Trust |
- Submission date
- 14/02/2025
- Registration date
- 03/04/2025
- Last edited
- 14/02/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Stickler syndrome is a genetic condition passed from parents to children that affects collagen, a key protein in the body's connective tissues. This can lead to problems with joints, the roof of the mouth, hearing, and eyes. The most common type, type 1 Stickler syndrome, can cause retinal detachment, leading to sight loss and potential blindness. While there is a treatment to prevent retinal detachment, early diagnosis is crucial to offer this treatment before sight is lost.
Our study aims to create a screening tool to identify important medical and family history associated with Stickler syndrome. We will test this tool in patients already diagnosed with Stickler syndrome and compare it to children without the condition. We will then use the tool in children with Perthes disease, a separate rare disease affecting the hip joint, to see if any have signs of Stickler syndrome. If successful, this tool could help diagnose patients earlier and offer treatment to prevent sight loss.
Who can participate?
Participants with Stickler syndrome will be selected from patients under our team and through the Stickler Syndrome UK charity's membership survey. A random sample of paediatric patients will also be selected from the general paediatric clinic in Cambridge. For testing in the Perthes disease population, participants will be selected from the paediatric orthopaedic Perthes disease clinic in Liverpool.
What does the study involve?
Participants will complete a screening tool, which takes about 10 minutes and includes a short examination of the child's mouth and joints. Children with Perthes disease will also have a blood test to check for a genetic variant causing type 1 Stickler syndrome.
What are the possible benefits and risks of participating?
The study aims to benefit future patients by identifying Stickler syndrome earlier and providing sight-saving treatment. For children with Perthes disease, the study may diagnose Stickler syndrome, leading to urgent assessment and management. The risks are minimal, with the screening tool being non-invasive and the blood test having the usual risks of distress and bruising.
Where is the study run from?
The study is run by the Vitreoretinal Research Group in the Department of Clinical Neurosciences at the University of Cambridge, in collaboration with the Paediatric Orthopaedic Department at Alder Hey Hospital in Liverpool (UK)
When is the study starting and how long is it expected to run for?
October 2024 to October 2026
Who is funding the study?
Addenbrooke's Charitable Trust Clinical Research Fellowship
Cambridge Trust Cambridge Masters & Churchill College Studentship (UK)
Who is the main contact?
Robert Smyth, rs815@cam.ac.uk
Contact information
Public, Scientific, Principal investigator
Vitreoretinal Research Group
John van Geest Centre for Brain Repair, University of Cambridge
Forvie Site, Robinson Way
Cambridge
CB2 0PY
United Kingdom
 ORCID ID |
0000-0001-9482-5123 |
|---|---|
| Phone | +44 1223 331160 |
| rs815@cam.ac.uk |
Principal investigator
Vitreoretinal Research Group
John van Geest Centre for Brain Repair, University of Cambridge
Forvie Site, Robinson Way
Cambridge
CB2 0PY
United Kingdom
| ORCID ID |
0000-0003-0042-8659 |
|---|---|
| Phone | +44 1223 331160 |
| mps34@cam.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Observational cross-sectional multicentre study |
| Secondary study design | Cross sectional study |
| Participant information sheet | 46850 Patient Information Sheet 1 - Perthes-Stickler Case Series.pdf |
| Scientific title | A cross-sectional study screening for Stickler syndrome in children diagnosed with Perthes disease |
| Study objectives | Stickler syndrome is present in the paediatric Perthes disease population and can be identified with a screening tool |
| Ethics approval(s) |
Not yet submitted |
| Health condition(s) or problem(s) studied | Screening for Stickler syndrome in paediatric Perthes disease patients |
| Intervention | A screening tool for Stickler syndrome will be developed using past medical and family history for patients under Cambridge University Hospitals NHS Trust (CUH) and identified by Stickler Syndrome UK charity patient membership survey, who have been co-diagnosed with Stickler syndrome and Perthes disease. This tool will then be ratified using paediatric patients with and without Stickler syndrome in CUH. Finally, the screening tool will be applied to paediatric patients with Perthes disease in Alder Hey hospital, Liverpool, with a genetic blood test for type 1 Stickler syndrome (COL2A1) collected at the same time. Patients' genetic results will be compared to their screening tool results, and the identification of any Stickler syndrome patients amongst this cohort will be considered a successful study outcome. |
| Intervention type | Other |
| Primary outcome measure(s) |
Type 1 Stickler syndrome genetic test, EDTA 1ml blood sample for COL2A1 long range PCR at baseline |
| Key secondary outcome measure(s) |
Screening tool results, past medical and family history of Stickler syndrome, obtained via questionnaire at baseline in all participants |
| Completion date | 02/10/2026 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | All |
| Lower age limit | 0 Years |
| Upper age limit | 99 Years |
| Sex | All |
| Target sample size at registration | 300 |
| Key inclusion criteria | We will have different cohorts at each stage of our study: 1. Design of screening tool: 1.1. Stickler syndrome patients participating in the SSUK patient membership survey 1.2. Stickler syndrome patients with a diagnosis of Perthes disease 2. Ratification of screening tool: 2.1. Stickler syndrome patients aged 4-10 years 2.2.General paediatric patients without a diagnosis of Stickler syndrome aged 4-10 years 3. Screening of Perthes disease population: 3.1. All paediatric patients attending paediatric orthopaedic Perthes disease clinics |
| Key exclusion criteria | We have different cohorts at each stage of our study: 1. Design of screening tool 1.1. Paediatric patients in SSUK patient membership survey without a Perthes disease diagnosis (as will be used in cohort 2) 2. Ratification of screening tool 2.1. Patients with a diagnosis of Perthes disease, being investigated for Perthes disease 2.2. General paediatric patients under investigation for a connective tissue disorder other than Stickler syndrome 3. Screening of Perthes disease population: 3.1. Previous genetic diagnosis of Stickler syndrome |
| Date of first enrolment | 01/03/2025 |
| Date of final enrolment | 01/06/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Eaton Road
West Derby
Liverpool
L12 2AP
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request, Published as a supplement to the results publication |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be published as a supplement to the results publication. Prior to publication the datasets generated during and/or analysed during the current study will be available upon request from Robert Smyth on rs815@cam.ac.uk. All shared data will be anonymised to protect patient confidentiality, and any data that may compromise patient confidentiality will be withheld. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 1 - Perthes-Stickler Case Series | 14/02/2025 | No | Yes | |
| Participant information sheet | 2 - Ratification | 14/02/2025 | No | Yes | |
| Participant information sheet | 3 - Perthes Screen | 14/02/2025 | No | Yes | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | version 1 | 13/02/2025 | 14/02/2025 | No | No |
Additional files
- 46850 Smyth Stickler Research Protocol 13Feb2025 v1.pdf
- Protocol file
- 46850 Patient Information Sheet 1 - Perthes-Stickler Case Series.pdf
- 1 - Perthes-Stickler Case Series
- 46850 Patient Information Sheet 2 - Ratification.pdf
- 2 - Ratification
- 46850 Patient Information Sheet 3 - Perthes Screen.pdf
- 3 - Perthes Screen
Editorial Notes
14/02/2025: Trial's existence confirmed by Addenbrooke's Charitable Trust.
