Early diagnosis of Stickler syndrome using a screening tool in children with Perthes disease

ISRCTN	ISRCTN86229394
DOI	https://doi.org/10.1186/ISRCTN86229394
IRAS number	343181

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

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

Dr Robert Smyth
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
Email	rs815@cam.ac.uk

Mr Martin Snead
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
Email	mps34@cam.ac.uk

Study information

Study design	Observational cross-sectional multicentre study
Primary study design	Observational
Secondary study design	Cross sectional study
Study setting(s)	Hospital, Medical and other records
Study type	Screening
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	Type 1 Stickler syndrome genetic test, EDTA 1ml blood sample for COL2A1 long range PCR at baseline
Secondary outcome measures	Screening tool results, past medical and family history of Stickler syndrome, obtained via questionnaire at baseline in all participants
Overall study start date	02/10/2024
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	Both
Target number of participants	Total sample size: 300. 1) Design of screening tool: use of patients from Perthes case series plus others diagnosed with Perthes disease (estimated 30), and patients from Stickler Syndrome UK patient membership survey (estimated 50). 2) Ratification of screening tool: 26 paediatric Stickler syndrome patients and 26 general paediatric patients. 3) Screening of Perthes disease population: paediatric patients from Perthes disease cohort (estimated 100-200).
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

England
United Kingdom

Study participating centres

Cambridge University Hospitals NHS Foundation Trust

Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Alder Hey Children's NHS Foundation Trust

Alder Hey Hospital
Eaton Road
West Derby
Liverpool
L12 2AP
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Hospital/treatment centre

Research and Development Department
Cambridge University Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

Phone	+44 1223 348490
Email	cuh.research@nhs.net
Website	https://www.cuh.nhs.uk/our-research/get-involved/become-a-researcher/
"ROR"	https://ror.org/04v54gj93

Funders

Funder type

Charity

Addenbrooke's Charitable Trust, Cambridge University Hospitals
Private sector organisation / Other non-profit organizations

Alternative name(s): Addenbrooke's Charitable Trust, Cambridge University Hospitals NHS Foundation Trust, ACT
Location: United Kingdom

Cambridge Commonwealth European and International Trust

No information available

Results and Publications

Intention to publish date	01/10/2027
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request, Published as a supplement to the results publication
Publication and dissemination plan	Planned publication in a peer-reviewed journal. Planned presentation at relevant conferences. Publication of results on SSUK website, newsletter and social media.
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
Protocol file	version 1	13/02/2025	14/02/2025	No	No

Additional files

46850 Smyth Stickler Research Protocol 13Feb2025 v1.pdf
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.