An observational longitudinal study of congenital myasthenic syndromes

ISRCTN	ISRCTN18340272
DOI	https://doi.org/10.1186/ISRCTN18340272
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	289835
Protocol serial number	1/090421, IRAS 289835
Sponsor	Oxford University Hospitals NHS Trust
Funder	Amplo Biotechnology Inc.

Submission date: 06/10/2022
Registration date: 28/11/2022
Last edited: 21/10/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

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

Mrs Hayley Ramjattan
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
Email	orh-tr.cmsgenetics@nhs.net

Study information

Primary study design	Observational
Study design	Observational exploratory study
Secondary study design	Cohort study
Study type	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(s)	Muscle fatigue measured using the following assessments: Quantitative Myasthenia Gravis (QMG) score at baseline, 6, 12 and 18 months
Key secondary outcome measure(s)	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)
Completion date	31/05/2024

Eligibility

Participant type(s)	Patient
Age group	All
Lower age limit	0 Years
Upper age limit	100 Years
Sex	All
Target sample size at registration	50
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

United Kingdom
England

Study participating centre

John Radcliffe Hospital

Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Stored in non-publicly available repository
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?
Basic results		21/10/2025	21/10/2025	No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN18340272_BasicResults_21Oct25.pdf: Basic results

Editorial Notes

21/10/2025: Basic results uploaded.
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.