A study to understand the early stages of muscle weakness in people with Dysferlinopathy (a type of limb girdle muscular dystrophy)
| ISRCTN | ISRCTN83128058 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN83128058 |
| IRAS number | 342366 |
| Secondary identifying numbers | Protocol Number: 10966 v1.1 |
- Submission date
- 16/10/2025
- Registration date
- 27/10/2025
- Last edited
- 20/10/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Limb Girdle Muscular Dystrophy R2 (LGMDR2), also called Dysferlinopathy, is a rare inherited condition that causes muscles to become weaker over time. It usually starts in the teenage years or early adulthood, but some people find out they have it through genetic testing before they feel any symptoms. Scientists still don’t know much about what happens in the very early stages of the disease. This study aims to learn more about those early changes in the body to help improve diagnosis and treatment in the future.
Who can participate?
People who have been diagnosed with changes in the DYSF gene (linked to Dysferlinopathy) and who either have no symptoms or only very mild symptoms may be invited to take part.
What does the study involve?
Participants will visit the research centre once a year for up to five years. Each visit will include:
-A physical check-up and tests of muscle strength and movement
-A walking assessment
-MRI scans to look at muscles
-Questionnaires about daily activity, tiredness, pain, and quality of life
-Blood and urine samples for lab tests
-Participants can also choose to give extra samples (like blood, skin, or muscle) for future research.
What are the possible benefits and risks of participating?
There is no direct benefit to participants, but the study will help doctors understand how the disease starts and changes over time. This could lead to better care and new treatments in the future. The risks are low and mostly related to standard medical procedures like blood tests or MRI scans.
Where is the study run from?
Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
April 2024 to December 2031
Who is funding the study?
Jain Foundation (USA)
Who is the main contact?
stephen.wandera@newcastle.ac.uk
volker.straub@newcastle.ac.uk
Heather.Hilsden@newcastle.ac.uk
Contact information
Scientific, Principal investigator
John Walton Muscular Dystrophy Research Centre
Institute of Genetic Medicine
Newcastle University
International Centre for Life
Newcastle upon Tyne
NE1 3BZ
United Kingdom
 ORCID ID |
0000-0001-9046-3540 |
|---|---|
| Phone | +44 191 241 8655 |
| volker.straub@newcastle.ac.uk |
Public
John Walton Muscular Dystrophy Research Centre
Institute of Genetic Medicine
Newcastle University
International Centre for Life
Newcastle upon Tyne
NE1 3BZ
United Kingdom
| Phone | +44 191 241 8635 |
|---|---|
| Heather.Hilsden@newcastle.ac.uk |
Study information
| Study design | Prospective observational longitudinal study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | COS-PREPARED: Clinical Outcome Study in PRe- and Early-symptomatic PAtients with REcessive Dysferlinopathy |
| Study acronym | COS-PREPARED |
| Study objectives | Primary objectives: 1. To describe and quantify the early natural history of Dysferlinopathy, including changes in muscle function, strength, and pathology, using physiotherapy assessments, gait analysis, and MRI measures. 2. To determine the most suitable and robust outcomes measures for evaluation of disease progression in patients with dysferlinopathy at early stages of the disease Secondary objectives: 1. To gain a greater understanding of symptom onset and muscle pathology at early disease stages for this patient population to inform earlier diagnosis. 2. To test current outcome measures sensitivity and suitability for assessing patients in the initial stages of symptom onset |
| Ethics approval(s) |
Approved 19/04/2024, North East - Newcastle & North Tyneside 1 Research Ethics Committee (2nd Floor, 2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8384; newcastlenorthtyneside1.rec@hra.nhs.uk), ref: 24/NE/0066 |
| Health condition(s) or problem(s) studied | Limb Girdle Muscular Dystrophy R2 (LGMDR2, Dysferlinopathy) |
| Intervention | Participants will visit the research centre once a year for up to five years. Each visit will include: -Physical Examination -Respiratory Assessment -Vital Signs -Functional Assessments -Care Discussion- access to current care -Strength Tests Dynamometry- pinch grip and hip adduction -Gait Assessment -Blood Draw -MRI Scan- 3 point Dixon, T2w mapping and Sodium MRI -Optional Biobanking- blood, urine, skin for fibroblast, muscle -Medical History |
| Intervention type | Other |
| Primary outcome measure | Muscle strength, function, and pathology measured using North Star Assessment for Limb Girdle Muscular Dystrophies (NSAD), timed functional tests (e.g., 100-metre walk/run), handheld dynamometry, and quantitative muscle MRI (3-point Dixon fat fraction and T2 mapping) at baseline and annually for up to 5 years |
| Secondary outcome measures | 1. Gait parameters (velocity, step length, symmetry, and muscle activation) measured using instrumented gait analysis with motion capture and surface electromyography at baseline and annually for up to 5 years 2. Activity limitation and participation measured using ACTIVLIM questionnaire at baseline and annually for up to 5 years 3. Fatigue and pain levels measured using Fatigue Severity Scale (FSS), PROMIS Fatigue, and Short-Form McGill Pain Questionnaire (SF-MPQ) at baseline and annually for up to 5 years 4. Respiratory function measured using Forced Vital Capacity (FVC) and FEV₁ in sitting and lying positions at baseline and annually for up to 5 years |
| Overall study start date | 19/04/2024 |
| Completion date | 31/12/2031 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 4 Years |
| Upper age limit | 65 Years |
| Sex | All |
| Target number of participants | 20 |
| Key inclusion criteria | 1. Genetically confirmed recessive Dysferlinopathy (LGMDR2), proven by two pathogenic or likely pathogenic variants in the DYSF gene 2. Pre-symptomatic or early-symptomatic individuals (able to stand on tiptoes on both feet and hop with foot clearance) 3. Able to perform all study assessments including muscle MRI and gait analysis 4. Able to attend scheduled annual visits and follow study procedures |
| Key exclusion criteria | 1. Current or planned medical or other interventions that could interfere with study assessments 2. Presence of another condition that could affect participation or study results, as judged by the investigator 3. Participation in a clinical trial that could alter the natural course of the disease |
| Date of first enrolment | 07/07/2025 |
| Date of final enrolment | 31/12/2029 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Sponsor information
Hospital/treatment centre
Freeman Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
England
United Kingdom
| Phone | +44 191 233 6161 |
|---|---|
| nuth.enquiries-nencchdn@nhs.net | |
| Website | https://www.newcastle-hospitals.nhs.uk/hospitals/freeman-hospital/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Jain Foundation Inc., JFI, JF
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/12/2030 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | All study results will be published and shared according to the COS-PREPARED Steering Committee and Publication and Data Access Policy. The Steering Committee, chaired by the Principal Investigator and including the Jain Foundation and study leads for physiotherapy, MRI, gait, and data management, will oversee all dissemination activities. Results from COS-PREPARED will be: - Submitted for presentation at international scientific and clinical conferences. - Published in peer-reviewed journals with full acknowledgement of the Jain Foundation and participating sites. - Summarised in lay language and shared with participants, the Jain Foundation, and patient advocacy groups. - Reported on publicly accessible research registries (ClinicalTrials.gov, ISRCTN) and institutional websites. All planned publications must be reviewed by the Steering Committee at least 30 days prior to submission to ensure scientific accuracy and appropriate authorship. Authorship will follow the International Committee of Medical Journal Editors (ICMJE) criteria. The Principal Investigator, relevant data leads, and Foundation representatives will be included as authors on all primary manuscripts. Access to de-identified study data may be granted to qualified researchers upon written request and approval by the Steering Committee. Commercial requests will be subject to formal agreements and cost recovery, while non-commercial academic requests will be provided free of charge. Participants will receive a lay summary of study results, and the Jain Foundation will help disseminate key findings to the wider Dysferlinopathy community. |
| IPD sharing plan | De-identified individual participant data, including clinical, physiotherapy, gait, MRI, patient-reported outcomes and biomarker results, will be available upon reasonable request from Heather Hilsden (Project Manager, JWMDRC, Newcastle University; heather.hilsden@newcastle.ac.uk or info@jwmdrc.org). Data will be stored in a secure non-public institutional repository at the John Walton Muscular Dystrophy Research Centre in collaboration with the Jain Foundation. Access will be granted after study completion and publication of the main results (expected from December 2030), subject to Steering Committee approval and a data-use agreement. Academic and non-commercial researchers may access de-identified datasets free of charge; commercial users may be asked to cover administrative costs. Data will remain available for at least 10 years post-publication and will comply with GDPR and UK Data Protection Act (2018) standards. Participants provide informed consent for anonymised data sharing for ethically approved research. |
Editorial Notes
16/10/2025: Trial's existence confirmed by North East - Newcastle & North Tyneside 1 Research Ethics Committee.
