An observational longitudinal study of congenital myasthenic syndromes
| ISRCTN | ISRCTN18340272 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18340272 |
| IRAS number | 289835 |
| Secondary identifying numbers | 1/090421, IRAS 289835 |
- Submission date
- 06/10/2022
- Registration date
- 28/11/2022
- Last edited
- 15/02/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Congenital myasthenic syndromes are characterized by muscle weakness (myasthenia) that worsens with physical exertion. The Oxford Highly Specialist CMS Service is running an observational natural history study to help understand the symptoms and problems people with congenital myasthenic syndromes (CMS) have. The researchers will do this by measuring muscle strength and fatigue and completing different questionnaires with participants. They can then compare which assessment scales are most suitable for people with different genetic subtypes. This will support future patient clinical care and help us to design future clinical treatment trials.
Who can participate?
Patients aged 0-100 years with a confirmed genetic diagnosis of CMS who attend the Oxford CMS centre for their study and clinical appointments for the duration of this study
What does the study involve?
All assessments will be completed alongside the participant's CMS clinic appointment in Oxford and will involve assessments that are part of a normal clinic review. As part of this study, participants will be asked to complete additional assessments, including physical exercises and questionnaires, plus optional assessments such as patient self-assessments to be completed at home and wearing an activity monitor. To complete these additional assessments the visit may take longer than usual, which could be up to 2 hours on average. The frequency of clinic appointments may increase, to ensure that participants are seen every 6 months, throughout the duration of the study.
What are the possible benefits and risks of participating?
There is no direct benefit to taking part, but this study will aid with the wider understanding of CMS. This is an observational study, and as such does not include any intervention. However, the study design involves completing a number of physical assessments to assess muscle fatigue and as a result may cause temporary muscle weakness. The researcher completing the assessments will mitigate this as far as possible by allowing rest breaks between assessments where able.
When is the study starting and how long is it expected to run for?
April 2020 to May 2024
Who is funding the study?
Amplo Biotechnology Inc. (USA)
Who is the main contact?
Hayley Ramjattan, orh-tr.cmsgenetics@nhs.net
Contact information
Principal Investigator
Children’s Therapies
Level LG1
The Children’s Hospital
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
| Phone | +44 (0)1865 231915 |
|---|---|
| orh-tr.cmsgenetics@nhs.net |
Study information
| Study design | Observational exploratory study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort 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 | A natural history study of congenital myasthenic syndromes to establish reliable outcome measures suitable for clinical and research assessment |
| Study objectives | To identify relevant and reliable outcome measures for assessing and monitoring change in the congenital myasthenic syndromes (CMS) population within the UK. |
| Ethics approval(s) | Approved 05/01/2022, London - Bromley Research Ethics Committee (Temple Quay House, 2 The Square, Temple Quay, Bristol, BS1 6PN, UK; +44 (0)207 104 8063; bromley.rec@hra.nhs.uk), ref: 21/LO/0480 |
| Health condition(s) or problem(s) studied | Congenital myasthenic syndromes (CMS) |
| Intervention | This is an observational exploratory study, conducted within the Oxford CMS clinic appointment, forming part of routine patient care. This study is expected to last for 24 months, with recruitment in the first 6 months. Each participant will be followed up at 6 monthly intervals, which aligns with the majority of the patient’s clinical visits. This will aim to include 2-4 visits (including baseline). All assessments will be completed alongside the participant's CMS clinic appointment in Oxford and will involve assessments that are part of a normal clinic review. As part of this study, participants will be asked to complete additional assessments, including physical exercises and questionnaires, plus optional assessments such as patient self-assessments to be completed at home and wearing an activity monitor. To complete these additional assessments the visit may take longer than usual, which could be up to 2 hours on average. The frequency of clinic appointments may increase, to ensure that participants are seen every 6 months, throughout the duration of the study. |
| Intervention type | Other |
| Primary outcome measure | Muscle fatigue measured using the following assessments: Quantitative Myasthenia Gravis (QMG) score at baseline, 6, 12 and 18 months |
| Secondary outcome measures | Measured at baseline, 6, 12 and 18 months: 1. Muscle fatigue measured using the following assessments: Sit-to-stand in One Minute (STS1M), 10-metre run (10m run), 6-Minute Walk Test (6MWT) and stairs climb (ascend and descend) 2. Activity levels monitored between clinic visits using a wrist-worn accelerometer device (AX3), worn for 7 days post visit and a patient self-assessment diary, completing arm outstretched and STS1M daily at home for 7 days 3. Patient-reported outcome measures: 3.1. Mental wellbeing measured using the Hospital Anxiety and Depression Scale (HADS) 3.2. Physical health measured using EQ-5D-5L 3.3. Participation measured using Myasthenia Gravis Activities of Daily Living (MG-ADL) 4. For children under 4 years of age, motor skill is measured using the CHOP-INTEND and WHO motor milestones 5. The impact on caregivers of supporting an individual with CMS will be measured using the Care Giver Indirect and Informal Care Cost Assessment Questionnaire, completed once in the study by the participant's carer, parent, guardian, or partner (with their direct consent) |
| Overall study start date | 01/04/2020 |
| Completion date | 31/05/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | All |
| Lower age limit | 0 Years |
| Upper age limit | 100 Years |
| Sex | Both |
| Target number of participants | 50-80 |
| Total final enrolment | 50 |
| Key inclusion criteria | 1. Participants with a confirmed genetic diagnosis of CMS, who are referred to the Oxford CMS service for their clinical management 2. 0-100 years of age 3. Participant is willing and able to give informed consent for participation in the study 4. The participant must be able to understand written and spoken English 5. Able to attend clinic every 6 months for face-to-face assessment with a physiotherapist |
| Key exclusion criteria | 1. Non-CMS medically or psychological conditions that may affect the OCMs, as judged by the medical team 2. Participants not compliant/unable to attend regular reviews in Oxford 3. Participants involved in other CMS research (e.g. novel therapies), which may impact the study assessments |
| Date of first enrolment | 04/02/2022 |
| Date of final enrolment | 08/03/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Headington
Oxford
OX3 9DU
United Kingdom
Sponsor information
Hospital/treatment centre
OUH Research & Development
Joint Research Office
Second Floor, OUH Cowley
Unipart House Business Centre
Garsington Road
Oxford
OX4 2PG
England
United Kingdom
| Phone | +44 (0)300 304 7777 |
|---|---|
| ouh.sponsorship@ouh.nhs.uk | |
| Website | http://www.ouh.nhs.uk/ |
"ROR" |
https://ror.org/03h2bh287 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository |
| Publication and dissemination plan | The findings from this study will be published in a peer-reviewed journal and made available at national and international conferences. The results will be fed back at the CMS National Patient Day, held annually and a lay summary will be created and made available through the MyAware charitable webpage. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a non-publicly available repository. Data will be stored on the CMS Tissue Bank clinical database (CMS TB database), which is the clinical database established for the CMS service. This database is held on REDCAP. Only designated members of the CMS clinical team and study team will have access. All the participants in the study will need to have already consented to their data being recorded on the CMS TB database as part of routine clinical care. Data will be collected from relevant medical history and physical assessments during their routine clinical visit. Participants will be identified through their CMS TB database reference number. This number will also then be their participant study number, which will be used throughout the study. All data entered into the CMS TB database will be retained for the length of time the participant is a patient under the Oxford CMS service. If they leave the service, participants will be offered the option for their data to remain part of the CMS TB database for longer-term analysis. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
15/02/2024: The following changes were made to the trial record:
1. The overall study end date was changed from 04/02/2024 to 31/05/2024.
2. The intention to publish date was changed from 04/02/2025 to 01/06/2025.
16/03/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 04/02/2023 to 08/03/2023.
2. The total final enrolment was added.
12/10/2022: Trial's existence confirmed by the London - Bromley Research Ethics Committee.
